Abstracts and Case Studies From the College of American Pathologists 2008 Annual Meeting (CAP '08)

Anonymous
Archives of Pathology & Laboratory Medicine

Aug 31, 2008 20:00 EDT

Abstract and case study poster sessions will be conducted during the College of American Pathologists Annual Meeting (CAP '08), which is scheduled for September 25 to September 28, 2008. The meeting will take place at the Manchester Grand Hyatt, San Diego, Calif. The poster sessions will occur in the Connection Café and Exhibits Hall. Specific dates and times for each poster session are listed below. Also shown below each poster session listing are the subject areas that will be presented during that session.

POSTER SESSION 100: THURSDAY, SEPTEMBER 25, 2008, 10:00 AM-12:30 PM

Hematopathology

Posttransplant Lymphoproliferative Plasma Cell Myeloma With t(8;14) and Epstein-Barr Virus Association

(Poster No. 1)

Rebecca M. Wilcoxon, MD (rebecca-wilcoxon@uiowa.edu); Michel R. Nasr, MD; Nancy Rosenthal, MD. Department of Pathology and Laboratory Medicine, University of Iowa Hospitals and Clinics, Iowa City.

Although posttransplant lymphoproliferative disorders are not rare, those presenting as plasma cell myeloma, particularly with plasmablastic morphology, are exceedingly uncommon. In this case, cytogenetic studies also revealed a t(8;14) translocation, which to our knowledge has not been previously reported in this setting. The patient was a 57-year-old man and cardiac transplant recipient who presented with lytic bone lesions and an IgG-λ monoclonal protein. Bone marrow examination revealed 60% atypical plasma cells with blastic morphology (Figure 1). Flow cytometric analysis of the atypical plasma cells showed CD38, CD138, and CD19 expression with surface λ light-chain restriction. CD56 was negative. Additionally, the tumor cells were Epstein-Barr virus-encoded RNA positive, and cytogenetics showed a t(8;14) translocation and trisomy 22. Despite aggressive therapy, the patient had a rapidly progressive disease course and died within 3 months of diagnosis. Posttransplant lymphoproliferative disorders presenting as plasma cell myeloma are exceedingly rare, with fewer than 20 cases reported in the literature. Furthermore, few of the reported posttransplant plasma cell myelomas are documented as being related to Epstein-Barr virus infection, and none of the cases describe cytogenetic abnormalities. The c-myc oncogene dysregulation of the cell cycle associated with the t(8;14) translocation may have led to the blastic morphology and may have contributed to the aggressive nature of the malignancy in this patient. This case contributes to the spectrum of diseases that may be seen in immunosuppressed patients after transplantation.

Gastric Extranodal Marginal Zone Lymphoma in Histologic Remission With a Recurrent Clonal B-Cell Population Detected in the Thyroid by Polymerase Chain Reaction

(Poster No. 2)

Kenneth E. Youens, MD (kenneth.youens@duke.edu); Jennifer H. Crow, MD; Michael B. Datto, MD, PhD. Department of Pathology, Duke University Medical Center, Durham, NC.

Extranodal marginal zone lymphoma of lymphoid tissue (MALToma) is an indolent B-cell neoplasm that is thought to arise as a result of chronic antigenic stimulation of mucosa-associated lymphoid tissue, which is frequently caused by infection in or inflammation of the affected site. In this setting, antigenic stimulation results in a polyclonal T-cell response that is thought to promote a monoclonal B-cell proliferation via a cytokinemediated mechanism. The most common chromosomal abnormality associated with MALToma is t(11;18)(q21;q21). It results in fusion of the inhibitor of apoptosis gene on chromosome 11 with the MALT lymphoma-associated translocation gene on chromosome 18, resulting in a more aggressive lymphoma that is less responsive to antibiotic treatment. We present a case in which gastric MALToma with a monoclonal t(11;18) Bcell population was brought to histologic remission by radiotherapy. Two years later, in the absence of further clinically malignant behavior, a monoclonal B-cell population with t(11;18) and an identical immunoglobulin heavy-chain rearrangement size to the gastric MALToma was identified in the thyroid gland in the setting of Hashimoto thyroiditis. This finding raises questions about the pathophysiology of MALToma. Speculatively, suppression of the accompanying polyclonal T cells by antibiotic or radiation therapy may decrease the cytokine-fueled proliferation of the clonal B-cell population, resulting in indolent posttherapy behavior of the B-cell clone. It may be plausible that in the setting of autoimmune disease, the residual monoclonal B cells can find an alternative inflammatory milieu that allows them to continue to proliferate.

Primary Cutaneous Precursor B-Cell Lymphoblastic Lymphoma: A Report of 2 Cases

(Poster No. 3)

Yvonne S. Noronha, MD (lynoronha@gmail.com); Jun Wang, MD. Department of Pathology, Loma Linda University Medical Center, Loma Linda, Calif.

Extramedullary precursor B-cell lymphoblastic lymphoma (pre B-LBL) is uncommon and tends to involve skin, soft tissues, and bones. We present 2 cases of primary cutaneous pre B-LBL. Case 1 was from a 6-yearold girl with a right cheek mass. Case 2 was from an 8-year-old boy with a left forehead mass. Both lesions were biopsied. Microscopically, both tumors showed a monotonous population of medium-sized lymphoid cells diffusely infiltrating the dermis with extension into the underlying subcutis and muscle. These lymphoid cells had high nuclear-cytoplasmic ratios, round to irregular nuclei with dispersed chromatin, multiple small nucleoli, and scant cytoplasm (Figure 2). Immunohistochemically, the neoplastic cells in case 1 expressed CD45, CD79a, PAX-5, CD10, CD34, and CD43 but not TdT or CD20. The neoplastic cells in case 2 expressed CD20, CD79a, PAX-5, CD10, and TdT but not CD3. Based on thorough physical examination and radiologic survey, peripheral blood and bone marrow involvement were not evident in either case; there was also no lymphadenopathy or other extranodal/medullary lesions. A diagnosis of primary cutaneous pre B-LBL was made in both cases. Pre B-LBL must be considered in the differential diagnosis of cutaneous "small round blue cell tumors," which includes primitive neuroectodermal tumor, rhabdomyosarcoma, neuroendocrine malignancies, granulocytic sarcoma, and other lymphomas. Pre B-LBL may show negative staining with commonly used panlymphoid markers like CD45 and B-cell markers like CD20 (case 1). Very rarely, TdT may be negative as well (case 1). Careful morphologic analysis along with appropriate immunophenotyping by flow cytometry and/or immunohistochemistry is essential in arriving at the right diagnosis.

Diagnosis of Copper Deficiency Myelodysplasia

(Poster No. 4)

Kathrina Alexander, MD (kathrina@uab.edu); Yongsheng Ren, MD, PhD; Vishnu Reddy, MD. Department of Pathology, University of Alabama-Birmingham.

Context: Copper deficiency has been cited as a rare and reversible cause of myelodysplasia, and the frequency of copper deficiencymyelodysplasia is unknown. Presently, clinical suspicion for copper deficiency as a cause of myelodysplasia is low. Additionally, the routine workup for myelodysplastic syndrome (MDS) does not include serum copper testing, creating the potential for misdiagnosis of MDS.

Design: During the first 4 months of 2007, bone marrow biopsies were performed on 56 patients, testing for possible MDS.

Results: In this cohort, 3 patients demonstrated marrow morphology that we believe to be consistent with copper deficiency, including cytoplasmic vacuolization of early erythroid and early myeloid precursors, left-shifted granulopoiesis, and granular iron deposits within plasma cells (Figure 3). Serum copper measurements performed on each of these 3 patients revealed undetectable or markedly deficient levels of copper. In each case, hematologic remission was rapidly achieved with copper supplementation.

Conclusions: We conclude that the frequency of copper deficiency myelodysplasia is higher than previously thought. Given the lack of routine serum copper testing in the evaluation of MDS, copper deficiency may be overlooked as the etiology of myelodysplasia and misdiagnosed as MDS, and patients with this curable condition may undergo unnecessary bone marrow transplantation. We suggest that the presence of vacuolization in both early erythroid and early myeloid lineage cells, and the presence of granular iron deposits within plasma cells, together represent hallmark morphologic features of copper deficiency. In our opinion, serum copper testing should be routinely performed in the evaluation for MDS in the presence of these morphologic features.

Spontaneous Tumor Lysis Syndrome and Secondary Thrombotic Thrombocytopenic Purpura in Early Stage Colorectal Cancer

(Poster No. 5)

Husain A. Saleh, MD, MBA1 (hsaleh@dmc.org); Saad Z. Usmani, MD2; Joel Apple, MD1; Zainab Shahid, MD.1 1Department of Pathology, Wayne State University, Detroit, Mich; 2Department of Hematology-Oncology, University of Connecticut Health Center, Farmington.

Spontaneous tumor lysis syndrome and secondary thrombotic thrombocytopenic purpura are oncologic emergencies that can occur at the onset of hematologic malignancies prior to treatment. They have been very rarely documented in solid tumors. We report a case of a 60-year-old woman with limited stage colorectal cancer presenting with these complications. The patient presented with a history of diarrhea with blood clots and leftsided abdominal pain. Computed tomography scan of the abdomen and pelvis showed diffuse colitis. Colonoscopy revealed a fungating mass obstructing the sigmoid colon, and the histopathology of the biopsy showed well-to moderately differentiated colonic adenocarcinoma. The patient rapidly developed spontaneous tumor lysis syndrome, including acute renal failure. She also developed thrombotic thrombocytopenic purpura with low hemoglobin and platelet levels and with a blood smear showing a microangiopathic hemolytic picture. Distal colectomy revealed stage IIA disease. Her renal function and blood counts returned to normal after surgery. To our knowledge, there are only 4 reported cases of spontaneous tumor lysis syndrome and 8 reported cases of secondary thrombotic thrombocytopenic purpura in solid tumors, all presenting with advanced stage metastatic disease. We report the first case of limited stage colorectal cancer presenting with both spontaneous tumor lysis syndrome and secondary thrombotic thrombocytopenic purpura.

Abnormal B-Cell Populations in 2 Patients With Whipple Disease

(Poster No. 6)

Leonard Grosso, MD, PhD; Emily S. Popovic, DO (popovice@slu.edu). Department of Pathology, Division of Hematopathology, St Louis University Hospital, St Louis, Mo.

Patients with Whipple disease (WD), a rare systemic disorder caused by the bacillus Tropheryma whippleii, most commonly exhibit gastrointestinal symptoms; however, lymph node involvement has been described. We present flow cytometric analysis of 2 lymph node biopsies in individuals ultimately diagnosed with WD. Analysis of the first lymph node (at an outside institution) identified a monoclonal population of B cells expressing κ light chain (moderate), CD19, CD20, CD22, CD38 (dim), CD45 (bright), and CD71 (subset) and representing 24% of cells of the retroperitoneal node. This population lacked CD5, CD10, CD11c, and CD23 and was identified by flow cytometry as a minor component of a bone marrow biopsy. Flow cytometic analysis of a mesenteric node in the second case identified an abnormal population of B cells (43% of cells) lacking surface light-chain expression. In both cases, polymerase chain reaction did not identify a monoclonal population of B cells, and there was no morphologic evidence of malignant lymphoma. Histiocytes containing T whippleii were identified by diastase-resistant periodic acid-Schiff staining and electron microscopy. Speculation on the pathogenesis of WD has suggested an immune derangement; the aberrant B-cell populations identified in these 2 cases (and in a previous report) may be reflective of this problem. Few cases of WD have been analyzed by immunophenotyping; therefore, the frequency of this aberrant response is unknown, and further study is necessary to confirm this hypothesis. Because of the potential misinterpretation of flow cytometric data in a patient with lymphadenopathy, caution should be exercised when that patient may have WD.

8p11 Stem Cell Leukemia: Simultaneous Presentation With Precursor B-Acute Lymphoblastic Leukemia, Precursor T-Lymphoblastic Lymphoma, and Myeloproliferative Syndrome

(Poster No. 7)

Ian M. Bovio, MD (boviim@pathology.ufl.edu); Robert W. Allan, MD. Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville.

The 8p11 stem cell leukemia/lymphoma syndrome is a rare, aggressive hematopoietic malignancy that is typically characterized by the coexistence of a chronic myeloproliferative disorder with hypereosinophilia and lymphoblastic lymphoma usually of T-cell type. We report the first case of myeloproliferative disorder occurring simultaneously with hypereosinophilia, precursor B-lymphoblastic leukemia, and precursor T-lymphoblastic lymphoma involving the bone marrow in a patient with a t(8; 13)(p12;q12) translocation. A 56-year-old previously healthy man presented with extensive lymphadenopathy and leukocytosis (white blood cell 30 000/µL). The peripheral blood was remarkable for eosinophilia (17%) and leukoerythroblastic features; flow cytometry was negative for an abnormal T- or B-lymphoblast population. A bone marrow biopsy and aspirate were performed, which revealed a precursor B-lymphoblastic leukemia (CD19^sup +^, CD10^sup ++^, CD20 dim/partial^sup +^, CD34^sup +^, TdT^sup +^), a small abnormal precursor T-cell population (surface CD3^SUP -^, cytoCD3^sup +^, CD7^sup +^, CD4^sup +^, CD8^sup +^, CD1a^sup +^), and a striking increase in eosinophils with myeloid predominance (myeloid-erythroid ratio of 10:1) that is consistent with a myeloproliferative disorder. The lymph node was extensively involved by precursor T-lymphoblastic lymphoma with the same immunophenotype of the marrow infiltrate and contained numerous eosinophils; precursor B-lymphoblastic lymphoma was not detected. Cytogenetic analysis on the bone marrow and peripheral blood and lymph node specimens revealed a t(8;13)(p12;q12) translocation. This case highlights the importance of careful morphologic and flow cytometric analysis, even when a singular diagnosis is prominent, to expand the spectrum of presentations of the 8p11 stem cell leukemia syndrome.

Cytotoxic T-Cell Lymphomas in Patients With B-Cell Chronic Lymphocytic Leukemia Appear to Be Derived From the Acquired Immune System

(Poster No. 8)

David A. Barrett, MD (barrett.david@mayo.edu); Andrew Feldman, MD; William Morice, MD, PhD; William Macon, MD. Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minn.

Context: Cytotoxic peripheral T-cell lymphomas (PTCLs) have been described as second lymphoid neoplasms in patients with B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma. To further characterize PTCLs associated with B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma, we studied 6 such cases from the surgical pathology files of the Mayo Clinic.

Design: Clinical data, histopathology, and immunochemistry results were reviewed for all 6 cases. Granzyme M staining was performed at the Mayo Clinic using a home-brewed antibody.

Results: The PTCLs were classified as follows: PTCL unspecified (4), subcutaneous panniculitis-like T-cell lymphoma (1), and anaplastic large cell lymphoma (1). All had an activated cytotoxic lymphocyte phenotype (TIA-1 and granzyme B positive), and most had T-cell phenotypic aberrancy (Table). None had granzyme M-positive tumor cells. However, some nonneoplastic T cells within the cellular reaction were granzyme M positive. Cytotoxic T-cell lymphomas in patients with B-cell chronic lymphocytic leukemia appear to be derived from the acquired immune system.

Conclusions: In this series, all PTCLs associated with B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma had an activated cytotoxic T-cell phenotype. None of the cytotoxic PTCLs expressed granzyme M, which suggests they had an origin from the acquired immune system. Of interest, reactive T cells included a subset that was granzyme M positive, suggesting these cells had an origin from the innate immune system.

Bone Marrow Granulomata and Hemophagocytosis in a Patient With Epstein-Barr Virus Infection

(Poster No. 9)

Anna D. Castiglione Richmond, MD (anna.d.castiglione.richmond@uth.tmc.edu); Wei Feng, MD; Meredith Reyes, MD; Andy Nguyen, MD. Department of Pathology, University of Texas-Houston.

Epstein-Barr virus (EBV) infection is known to cause hemophagocytic syndrome. Granulomata in the bone marrow have also been associated with viral infections, such as EBV. However, it is rare to have both hemophagocytic syndrome and granulomata in the bone marrow due to an EBV infection. We present a case of hemophagocytic syndrome and bone marrow granulomata after primary EBV infection. The patient, a previously healthy 13-year-old girl, presented with fevers for 2 weeks. A peripheral blood smear showed pancytopenia and microcytic hypochromic anemia with minimal reticulocytosis. The bone marrow was normocellular with increased erythropoiesis. The bone marrow aspirate demonstrated many macrophages containing phagocytosed erythrocytes and myelocytes. Focal granulomata were also seen in the bone marrow biopsy. Neither acid-fast bacilli nor fungal organisms were identified on acid-fast and Gomori methenamine-silver stains, respectively. However, EBV-latent membrane protein immunohistochemical stain, and EBV in situ hybridization performed on the bone marrow biopsy, showed positivity within the granulomata. The nongranulomatous areas of the biopsy were negative. Serology for EBV indicated a latent infection, with positive EBV immunoglobulin (Ig) G antibodies to viral capsid antigen and EBV IgG antibodies to nuclear antigen while being negative for EBV IgM antibodies to viral capsid antigen and EBV IgG antibodies to early antigen. The constellation of clinicopathologic findings are consistent with EBV-induced hemophagocytosis and granulomata resulting in pancytopenia. To our knowledge, the presentation in a patient with EBV infection of concurrent findings of hemophagocytosis and granulomata on the bone marrow biopsy, with positivity for EBV latent membrane protein and Epstein-Barr-encoded ribonucleic acids, has never been described.

Immunoglobulin D-Positive Lymphocytic and/or Histiocytic Reed-Sternberg Cell Variants in Nodular Lymphocyte-Predominant Hodgkin Lymphoma

(Poster No. 10)

Syed S. Ahmed, MD (taahas@yahoo.com); Majd Jundi, MD. Department of Pathology, Al-Hada and Taif Military Hospital, Taif, Saudi Arabia.

Immunoglobulin D (IgD)-positive lymphocytic and/or histiocytic Reed-Sternberg cell variants (L&H cells) are a unique subset of nodular lymphocyte-predominant Hodgkin lymphoma. A 5-year-old boy presented with enlarged solitary submandibular lymph node of 6 months' duration. There were no associated B symptoms, such as fever or weight loss. Excision biopsy of the lymph node showed diffuse effacement of the nodal architecture by proliferation of atypical lymphocytes containing abundant Reed-Sternberg-like L&H cells. Focal residual lymphoid follicles were present. The L&H cells were positive for CD20, IgD, Oct2, Bcl-6, and Bob.1 and were negative for CD15 and CD30. There was an abundance of CD3-positive T lymphocytes in the background. IgD is usually coexpressed in the naive B cells (CD27 positive) and centroblast (CD38 positive). Approximately 25% of the nodular lymphocyte-predominant Hodgkin lymphoma show IgD-positive L&H cells in the interfollicular regions. These cases differ from IgD-negative nodular lymphocyte-predominant Hodgkin lymphoma in which the L&H cells are present in the disrupted B-cell follicles and are Pu.1 positive. Clinically, both IgD-positive and IgD-negative cases present as a solitary mass, but the IgD-positive cases are more prevalent in younger patients (21 vs 44 years) and have a striking male predominance (male-female ratio, 23:1 vs 1.5:1).

Derivative (16;17): A Novel Poor Outcome Indicator

(Poster No. 11)

Paula Andrea Rodriguez Urrego, MD1 (palaro@msn.com); Daphne Ang, MD1; Malca Kierson, DO1; Vathany Sriganeshan, MD2; Lauri Goodell, MD1; Hana Aviv, PhD.1 1Department of Pathology, Robert Wood Johnson Medical School/University of Medicine and Dentistry of New Jersey, New Brunswick; 2Department of Pathology, Mount Sinai Medical Center, Miami Beach, Fla.

Previous karyotypes involving chromosomes 16 and 17 have been associated with prognostic significance in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). There has generally been favorable response to therapy in patients with AML with inversion 16 or translocation (16;16) and unfavorable prognosis in cases of MDS and AML with deletions del(17p) and del(16q22). We present 3 AML patients, 1 therapy related and 2 with history of MDS, who shared the same abnormal karyotype detected by G-banding stain: 46,XY,der(16;17)(p10;q10),-17. This derivative chromosome resulted in simultaneous del(16q) and del(17p). Flow cytometry, bone marrow biopsy, demographics, clinical history, and outcome were compared. Morphologic changes associated with del(16q) or del(17p) were noted. Patients were followed with fluorescence in situ hybridization probe, core binding factor β subunit, for the persistence of del(16q). All patients were men, ranging in age from 69 to 80 years (Table). Flow cytometry in all patients was positive for CD34, CD117, CD13, CD33, and cytoplasmic myeloperoxidase with an average blast count of 22%. Although MDS abnormalities with poor prognosis were absent, the outcome was similar. To our knowledge, the clinical significance of der(16; 17) has not yet been described.

Verification and Establishment of Reference Intervals for Hematology and Biochemistry Parameters: A Study of Indian Men

(Poster No. 12)

Preeti Kabra, MD1 (preetiλkabra@relbio.com); Jagruti Desai, MSc2; Madhura Joshi, BSc, DMLT1; Neela Asarkar, BM Tech1; Jaikant Gaikwad, BSc, DMLT1; Ashwini Patil, BSc, DMLT1; Eileen Daniel, BA.1 1Central Laboratory and 2Department of Early Development, Reliance Clinical Research Services, Navi Mumbai, India.

Context: Few data are available in literature for reference intervals for healthy Indian populations. We conducted retrospective analyses of data from samples analyzed at our laboratory to establish reference intervals for Indian men.

Design: Analyses were conducted for 21 hematology parameters and 14 chemistry parameters using samples from 120 healthy men with body mass index ranging from 18 to 25 and with no significant disease or blood donation in the last 3 months. Criteria for verification were as follows: After mean and standard deviation calculations, if 10% or less of data points fell outside the manufacturer's proposed reference interval, then the interval was verified. If more than 10% of data points fell outside the manufacturer's proposed reference interval, the reference interval was established using parametric/nonparametric methods by applying the Anderson Darling test.

Results: The proposed reference interval was verified for most parameters. The eosinophil percentage in the Indian population differed significantly. The proposed reference interval for eosinophils was 0.8% to 7.0%. The interval established in Indians was 0.0% to 12.4%. For hemoglobin, the proposed reference interval was 13.0 to 18.0 g/dL. The established reference interval was 11.9 to 16.4 g/dL. For routine chemistry parameters, the manufacturer's proposed reference interval was verified for all parameters, except for total protein and serum urea nitrogen. Serum urea nitrogen was slightly lower in the Indian population.

Conclusions: Eosinophil percentages in healthy Indian men was significantly higher, possibly due to environmental factors. Hemoglobin and serum urea nitrogen levels were lower compared with other populations, possibly due to nutritional factors and the Indian physique. We are planning studies using larger samples to verify the same from different geographical areas within India.

Bronchioloalveolar Lung Circulating Tumor Cells Retain Cytomorphologic Features of Primary Tumor Type

(Poster No. 13)

Dena Marrinucci, BS1 (dmarrinu@scripps.edu); Kelly Bethel, MD2; Jennifer Fisher, MD3; Daniel Lazar, BS1; Madelyn Luttgen, BS1; Peter Kuhn, PhD.1 1Department of Cell Biology, The Scripps Research Institute, La Jolla, Calif; Departments of 2Pathology and 3Oncology, Scripps Clinic, La Jolla, Calif.

Circulating tumor cell (CTC) detection and characterization could provide a valuable tool for stratifying cancer patients and aiding with individualized treatment strategies. We study a nonsmoking 47-year-old woman who was diagnosed with stage IIIB non-small cell lung cancer in 2003. She was treated with chemoradiation and consolidative Taxotere, but the cancer recurred locally in January 2005, and the patient subsequently received multiple agents secondary to progression. In 2007, 67 CTCs were identified using an immunofluorescent staining protocol and fiberoptic array scanning technology and then stained with Wright-Giemsa. The CTCs are larger than surrounding white blood cells, often appear in clusters, and have low to moderate nuclear-cytoplasmic (N/C) ratios and a generous cytoplasmic domain (Figure 4). Compared with the cells of the patient's original lung biopsy, which shows a well-differentiated bronchoalveolar carcinoma, the CTCs retain the morphologic features of large size in comparison to white blood cells and low N/C ratios with voluminous cytoplasm. The striking cytomorphologic difference between the CTCs in this patient with very well-differentiated adenocarcinoma, versus previously studied patients with less well-differentiated tumors of breast and colon, suggests that cytomorphologic features of primary tumors are retained when cells enter the bloodstream. The additional images demonstrate primary tumor and correlating CTC features in a breast cancer (cuboidal cells in tissue, round high N/C ratio cells in circulation), a colon cancer (columnar cells in tissue, elongated cells with eccentric cytoplasm in circulation), and this well-differentiated lung cancer (moderate to low N/C ratio cells in tissue, moderate to low N/C ratios in circulation).

Diffuse Large B-Cell Lymphoma With Aberrant T-Cell-Associated Antigen Expression

(Poster No. 14)

Archana M. Agarwal, MD (archana.agarwal@hsc.utah.edu); Jeremy Wallentine, MD; Kristi Smock, MD; David Bahler, MD, PhD; Sherrie Perkins, MD, PhD. Department of Pathology, University of Utah, Salt Lake City.

Diffuse large B-cell lymphoma (DLBL) is the most common type of non-Hodgkin lymphoma. Although, aberrant expression of T-cell-associated antigens (exclusive of CD5) on diffuse large B-cell lymphoma has been described in the literature, it is rare with few published reports. We describe 2 well-characterized cases of diffuse large B-cell lymphoma, 1 with aberrant coexpression of CD3 and the other showing aberrant expression of both CD2 and CD7. The literature of diffuse large B-cell lymphoma with aberrant T-cell-associated antigen expression was also reviewed. Case 1: A 9-year-old boy presented with a 2-month history of swelling in his left forearm. The left forearm biopsy showed a polymorphic background with scattered larger pleomorphic tumor cells. The tumor cells were positive for CD20, CD79a, PAX-5, and MUM-1 and also coexpressed CD3. Case 2: A 54-year-old woman presented with right inguinal lymphadenopathy. Immunohistochemical analysis on the paraffin sections revealed sheets of larger atypical cells positive for CD20, CD79a, and PAX-5 that also coexpressed CD2 and CD7. The expression of T-cell-associated antigens CD3, CD2, and CD7 by DLBL is important to recognize because it can greatly complicate diagnoses. To the best of our knowledge, CD3 expression by DLBL has not been previously reported in pediatric patients with DLBCLs. Although rare cases of B-cell lymphomas with expression of either CD2 or CD7 have been previously described, coexpression of both CD2 and CD7 by a DLBL also has not been previously described.

An Unusual Case of Acute Intravascular Hemolysis

(Poster No. 15)

Amanda C. Mullins, MD1 (amullin3@utmem.edu); Ted S. Strom, MD, PhD.2 1Department of Pathology, University of Tennessee-Memphis; 2Department of Pathology and Laboratory Medicine Service, Memphis VA Medical Center, Memphis, Tenn.

Hemolysis is a common problem in laboratory medicine and is a frequent cause of rejected specimens. The dilemma for pathologists lies in determining which case of hemolysis is in vitro and which is in vivo. The patient was a 53-year-old African American man with a medical history significant for end-stage renal disease on dialysis, hypertension, and hepatitis C. He presented from dialysis with a complaint of dull, substernal chest tightness, elevated blood pressure, and shortness of breath. Initial laboratory evaluation was hampered by severe, gross hemolysis of sampled blood. The results were remarkable for a total bilirubin level of 17.9 mg/dL, an aspartate aminotransferase level of 723 U/L, a hemoglobin level of 8.30 g/dL, a hematocrit concentration of 15.2%, and a lactate dehydrogenase level of 16 764 U/L. A direct antiglobulin test was negative. A peripheral smear was reviewed and showed moderate anisocytosis the red cell line with frequent polychromasia and occasional microspherocytes. No schistocytes, bite cells, or blister cells were seen. Leukocyte and platelet morphologies were unremarkable. Extensive evaluation the patient was negative for alternative sources of blood loss to account the precipitous drop in hematocrit concentration. This patient's acute intravascular hemolysis was attributed to a kink and/or clot in a dialysis line. Acute intravascular hemolysis induced by a kink and/or clot in a hemodialysis machine is rare. It is distinguished from other causes mainly history. Recognition of this entity by pathologists may prevent extensive evaluation and unnecessary procedures.

Primary Mucosa-Associated Lymphoid Tissue Lymphoma of the Breast With Localized Amyloidosis

(Poster No. 16)

Fadi Habib, MD (fhabib1@hfhs.org); Koichi Maeda, MD. Department Clinical and Anatomic Pathology, Henry Ford Health System, Detroit, Mich.

Primary non-Hodgkin lymphoma of the breast is a rare disease; however, the association between mucosa-associated lymphoid tissue lymphoma with localized amyloidosis makes it exceptional. We report on a 72-year-old woman who presented to the surgery clinic for consultation after abnormal mammogram. The screen mammogram detected a 10-mm area of asymmetry in the left breast. An ultrasound-guided needle biopsy showed extramedullary plasmacytoma with amyloid deposition, and excisional biopsy was advised. Initial evaluation revealed proliferation of small neoplastic lymphocytes, plasmacytoid lymphocytes, and plasma cells with focal deposits of amyloid-like material (Figure 5). In immunohistochemical stains, the lymphoid infiltrate included areas in which CD20-positive/CD79a-positive B cells and VS38-positive plasma cells predominated and other areas in which CD3-positive/CD5-positive/CD43-positive T cells were more numerous. The B cells were CD20 positive, CD5 negative (with no CD20/CD5 coexpression), CD43 negative, cyclin negative, and CD10 negative. The plasma cells were predominantly κ positive, and the amyloid-like material was Congo red positive. A clonal IGH gene rearrangement/monoclonal B-cell population was detected by molecular analysis. Cytogenetic study was normal. Subsequent abdominal fat-pad biopsy was done to rule out systemic amyloidosis. Serum protein electrophoresis was normal; however, urine protein electrophoresis and immunofixation showed traces of free κ light chain (<0.1 g per volume) in the fast γ region. To the best of our knowledge, very few cases of such association have been described in the English literature. The disease had a very indolent course, remaining localized to the organ, and it responded favorably to local radiation therapy.

Synchronous Lymphoblastic Lymphoma and Chronic Eosinophilic Leukemia With FIP1L1-PDGFRA Gene Fusion and Deletion of CHIC2

(Poster No. 17)

Summer L. Bohman, MD (DxAxNxCxEx@aol.com); John H. Irlam, DO; Robert L. Booth, MD. Department of Pathology, University of Toledo, Toledo, Ohio.

The association of the CHIC2 deletion with FIP1L1-PDGFRA fusion and primary eosinophilic disorders has gained recent interest as a group of disorders that appear to respond favorably to imatinib. We present a patient with synchronous lymphoblastic lymphoma and chronic eosinophilic leukemia, both with the CHIC2 gene deletion. Peripheral blood smears with bone marrow and lymph node biopsies were evaluated to diagnose synchronous malignancies. Flow cytometry and TdT stain were used to confirm lymphoma. Both blood myeloid cells and lymph node were tested for CHIC2 deletion by fluorescence in situ hybridization. The peripheral blood showed a chronic increase of eosinophils, approximately 30%. The bone marrow was hypercellular. The patient had evidence of heart valve disease and no other cause for eosinophilia could be found. The lymph node revealed complete effacement by malignant cells, which by flow cytometry was of a population of abnormal T cells. These cells were strongly positive for TdT, consistent with lymphoblastic lymphoma. Both the blood sample and the lymph node were positive for the CHIC2 deletion. Reactive eosinophilia is a common finding with lymphoblastic lymphoma. The CHIC2 deletion in both lymphoma and myeloid cell lines indicates a stem cell origin of bilineal chronic eosinophilic leukemia and lymphoblastic lymphoma. The importance of identifying patients with this mutation lies in the high reported rate of molecular remissions following imatinib treatment, which targets an abnormal tyrosine kinase that is created by the FIP1L1-PDGFRA gene fusion. This may lead to a decreased morbidity and mortality in these patients with early identification and treatment.

Small Lymphocytic Lymphoma Developed in an Anaplastic Astrocytoma in the Brain

(Poster No. 18)

Xiaohong M. Zhang, MD, PhD (xmzhang1@geisinger.edu). Department of Pathology, Geisinger Northeastern Medical Center, Wilkes-Barre, Pa.

Anaplastic astrocytoma is usually solitary. We report a case of a 72-year-old man with mixed tumors of anaplastic astrocytoma and small lymphocytic lymphoma in the brain. The patient had a history of B-cell chronic lymphocytic leukemia in peripheral blood with immunophenotypic features of positivity for CD19, CD20 (weak), coexpressing CD5 and CD23 with κ light-chain restriction by flow cytometry study. He was treated with Fludarabine and Rituxan twice. He developed moderate to severe headaches and unstable gait. A computed tomography scan of the brain showed a 7.7 × 5.3-cm mass with enhancing area in the right temporal lobe. Physical examination revealed neither peripheral lymphadenopathy nor hepatosplenomegaly. Neurologic examination showed equal pupils reactive to light and normal motor strength of all muscles. Laboratory tests revealed a white blood cell count of 15 810/µL with 94% lymphocytes. Temporal craniotomy was performed. The specimen revealed an anaplastic astrocytoma admixed with small lymphocytic lymphoma (Figure 6). The anaplastic astrocytoma showed marked nuclear atypia and some mitotic activity, but no necrosis or microvascular glomerulus. Small lymphocytic lymphoma had monotonous small lymphocytes with mature chromatin. Immunostains revealed astrocytoma positive for glial fibrillary acidic protein and small lymphocytic lymphoma positive for CD79a, CD5, and CD23. CD20 expression was weak. No other site of lymphoma was noted after careful examination. The patient recovered from craniotomy. To our knowledge, this finding has not been previously reported. This case demonstrates small lymphocytic lymphoma developed in an anaplastic astrocytoma and provides the evidence of brain histopathology in this rare situation.

A Collision Tumor: Central Nervous System B-Cell Lymphoma and Anaplastic Astrocytoma

(Poster No. 19)

Kun Ru, MD, PhD (kru@wpahs.org); Cufeng Pu, MD, PhD; Katherine Jasnosz, MD; Jan Silverman, MD; Shahid Bokhari, MD. Department of Pathology, Allegheny General Hospital, Pittsburgh, Pa.

Second malignancies are relatively common among long-term survivors following chemotherapy or radiation for the primary neoplasm. However, central nervous system (CNS) collision tumors in immune competent patients are extremely rare. We report a CNS collision tumor consisting of a primary CNS B-cell lymphoma and an anaplastic astrocytoma in a 29-year-old man without any significant medical history. The patient presented with a 4-week history of headaches, altered mental status, nausea, and vomiting. A computed tomography scan revealed a complex mass with surrounding edema at the left parietal lobe. Microscopically, the tumor showed 2 distinct histologic patterns. The predominant component consisted of anaplastic astrocytoma with gemistocytic appearance in the background of numerous lymphocytes. Multiple foci of perivascular lymphocytic aggregates were present, including many small lymphocytes with scattered large atypical cells. Immunostains highlighted that the large cells were CD20-positive B cells with a high proliferation index. In situ hybridization demonstrated that the neoplastic cells were κ restricted and Epstein-Barr virus positive, and molecular studies showed a clonal rearranged immunoglobulin gene. After the surgery and 5 cycles of methotrexate therapy, the patient is neurologically asymptomatic. The positive Epstein-Barr virus favors a virus-driven process in terms of the tumorigenesis. The diagnostic challenge in this case is the differential diagnosis between the reactive lymphocytes surrounding an existing glioma versus a lymphoproliferative disorder. We believe this is the first report of a simultaneous CNS collision tumor consisting of a primary CNS lymphoma and an anaplastic astrocytoma.

Precursor T-Lymphoblastic Lymphoma With Coexpression of T- and B-Cell Antigens: A Very Rare Occurrence

(Poster No. 20)

Christopher Dadisman, MD (dadics@pathology.ufl.edu); RobertW. Allan, MD. Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville.

Precursor T-lymphoblastic lymphomas often express aberrant myeloid markers, in particular CD13, CD33, and less frequently C-kit. The aberrant expression of markers of B-cell lineage by these tumors is extremely unusual and would make diagnosis difficult. We report a case of a precursor T-lymphoblastic lymphoma that aberrantly expressed the B-cell marker CD19 by flow cytometry and CD79a by immunohistochemistry. The patient was a 13-year-old girl who presented with cervical lymphadenopathy. A lymph node biopsy revealed an effaced lymph node composed of small cells with immature chromatin and scant cytoplasm. Flow cytometry was performed, which showed a homogenous blast population with a precursor T-cell phenotype: CD3^sup +^, CD2 dimly^sup +^, CD7^sup +^, CD5^sup +^, CD34^sup +^, CD33^sup +^, C-kit^sup +^, CD45 moderately^sup +^, CD56^sup +^, TdT^sup +^, myeloperoxidase^sup -^, CD1a^sup -^, and CD10^sup -^. The tumor aberrantly expressed surface CD19 and CD22 dimly (Figure 7). Immunohistochemical stains were positive for CD79a and negative for Oct-2. The bone marrow and peripheral blood were negative for leukemia. According to the European Group for the Immunological Characterization of Leukemias criteria, the case met criteria for biphenotypic leukemia based on the expression of CD19 and CD79a, although the latter is not infrequently observed in precursor Tlymphoblastic neoplasms. She was treated for precursor T-lymphoblastic lymphoma with vincristine, daunorubicin, prednisone, and asparaginase and maintenance 6-mercaptopurine. One year later she is in complete remission. In summary, we report a very rare lymphoblastic lymphoma with coexpression of T-cell and B-cell antigens, which highlights the lineage ambiguity that may occur in these neoplasms.

Biphenotypic Acute Leukemia in a Patient With Waldenström Macroglobulinemia After Long-Term Treatment With Chlorambucil

(Poster No. 21)

Mikako Warren, MD1; Stacey A. Honda, MD, PhD2; Jane H. Uyehara-Lock, MD2 (jhu@hawaii.edu). 1Department of Pathology, University of Hawaii Residency Program, Honolulu; 2Department of Pathology, Kaiser Moanalua Medical Center and University of Hawaii, John A. Burns School of Medicine, Honolulu.

Waldenström macroglobulinemia is a rare malignant lymphoproliferative disorder with immunoglobulin M monoclonal gammopathy. Chlorambucil, an alkylating agent, is commonly used to treat Waldenström macroglobulinemia; however, like other alkylating agents, there is a risk to the patient of developing myelodysplastic syndrome or in rare cases leukemia. We report the first case of a 75-year-old man who developed biphenotypic acute leukemia after 4½ years of treatment with chlorambucil for Waldenström macroglobulinemia. After 4½ years of treatment with chlorambucil, this 75-year-old patient presented with fever, weakness, and respiratory infection. His fever workup revealed a white blood cell count of 4300/µL, with a differential showing 46% poorly differentiated cells and 12% blasts. A bone marrow biopsy revealed a hypercellular marrow consistent with acute leukemia and residual lymphoplasmacytic infiltrate. The flow cytometric analysis was characteristic of a biphenotypic acute leukemia with residual lymphoplasmacytic lymphoma. It is unclear if the biphenotypic leukemia developed as a result of chlorambucil treatment or if this case represents de novo formation of leukemia in Waldenström macroglobulinemia.

Ceftriaxone-Induced Hemolysis: A Case Report of a Rare But Potentially Fatal Complication

(Poster No. 22)

Syed T. Hoda, MD (shoda@nshs.edu). Department of Pathology, North Shore-Long Island Jewish Medical Center, New Hyde Park, NY.

Cephalosporins are among the most widely used antibiotics in the hospital setting. Considering the number of patients given antibiotics such as ceftriaxone, severe complications resulting from these antibiotics are a rare event. A 6-year-old girl was admitted to the emergency department with fever and was positive for methicillin-resistant Staphylococcus aureus. She was subsequently being treated for methicillin-resistant S aureus with ceftriaxone. Twenty-four hours after the ceftriaxone was started and then discontinued, the patient experienced a large decrease in hemoglobin and hematocrit levels. Within 24 hours, the patient's hemoglobin/hematocrit levels went from 10.3/32.6 to an extremely low 1.3/4.3. A direct Coombs test was positive for C3d complement activity. A sample of blood from the severely anemic test was sent for antibody analysis. The results showed a positive antibody response to ceftriaxone on the red blood cells from this sample. This positive finding may have contributed to the low hemoglobin/hematocrit levels found in the patient's laboratory test results. Autopsy findings also documented cardiopulmonary anomalies in this patient. A literature search indicated that there are fewer than 40 known and documented cases of ceftriaxone-induced hemolysis. The positive antibodies to ceftriaxone found in this patient's blood make this antibiotic a very likely contributor to her death. If severe structural and congenital anomalies are combined with a severely traumatic drug-associated hemolytic reaction, as witnessed in this case, it is difficult to conceive of a good patient prognosis. Drug-induced hemolysis is a severe complication and should be considered when there is evidence of a rapid hemolytic reaction.

Acquired Expression of CD56 in Recurrent Diffuse Large B-Cell Lymphoma

(Poster No. 23)

Emily C. Maambo, MD (emaambo@umm.edu); Frank X. Zhao, MD; Christine McMahon, MD. Department of Anatomic Pathology, University of Maryland Medical Center, Baltimore.

Context: CD56, or neural cell adhesion molecule, plays a primary role in the regulation of homophilic interactions between neurons and muscle. It is also commonly expressed on the surface of natural killer cells. It is regarded as a poor prognostic marker in plasma cell myeloma and anaplastic large T-cell lymphomas. However, CD56 is usually negative in diffuse large B-cell lymphomas (DLBCL). Only 4 cases of CD56-positive DLBCL have been reported in the English literature. We identified a case of recurrent DLBCL that acquired CD56 expression in the second recurrence.

Design: To evaluate the relationship between the aberrant CD56 expression and the recurrence of DLBCL, we analyzed all the DLBCLs diagnosed at the University of Maryland Medical Center from 2004 to February 2008 (44 primary and 5 recurrent DLBCLs) using immunohistochemistry for CD56.

Results: Our study showed that CD56 expression was only detected in the second recurrent DLBCL sample of our index case. In addition, p53 was also positive in both the first and second recurrent biopsy samples for our index case.

Conclusions: We conclude that CD56 expression is rare in both the primary and possibly recurrent DLBCL. Because CD56 was acquired during the second recurrence of this DLBCL, it may play a role in the progression of DLBCL. In addition, the relationship between CD56 and p53 expression deserves further investigation in recurrent DLBCL.

A Case of True Thymic Hyperplasia Associated With Graves Disease

(Poster No. 24)

John J. Nelson, MD, MPH (jjnelson@usouthal.edu); Jacek M. Polski, MD. Department of Pathology, University of South Alabama, Mobile.

Mass lesions in the mediastinum are clinically worrisome and often of neoplastic origin; they include lymphoma, thymoma, and germ cell tumors. Thymic hyperplasia is not common but sometimes presents with a mediastinal mass. Thymic hyperplasia can involve normal thymic tissue (true thymic hyperplasia) or lymphoid follicles (follicular hyperplasia). Thymic hyperplasia is often associated with autoimmune phenomena, and the association of follicular thymic hyperplasia with myasthenia gravis is well known. Association of symptomatic true thymic hyperplasia with Graves disease has been reported only in rare case reports. We describe a single case report of true thymic hyperplasia associated with Graves disease. A 40-year-old white man presented with 4 days of difficult breathing. He reported a 20-lb weight loss during the last 6 months. Chest radiographs showed an enlarged cardiac silhouette. Computed tomography scan of the chest showed an anterior mediastinal mass adherent to the pericardium. The patient underwent excision of the mass. Postoperative laboratory workup documented Graves disease. The mass measured 11.5 × 7.0 × 2.0 cm and weighed 73 g. The microscopic examination showed thymic tissue with preservation of cortex and medulla with often enlarged Hassall corpuscles. This case illustrates an association of symptomatic true thymic hyperplasia with Graves disease. In most cases of Graves disease, the thymic hyperplasia is minimal and reversible on treatment. This reversible consequence of Graves disease should not be overlooked in the differential diagnosis, because we have the ability to treat the patient medically and to avoid sometimes unnecessary surgical intervention.

Extent of Bone Marrow Hemophagocytosis in Hemophagocytic Lymphohistiocytosis

(Poster No. 25)

Suman Goel, MD, MPH1 (sgoel@usouthal.edu); Hamayun Imran,MD2; Jacek M. Polski, MD.1 Departments of 1Pathology and 2Pediatrics, University of South Alabama, Mobile.

Context: Hemophagocytic lymphohistiocytosis (HLH) is a rare and potentially fatal disease characterized by abnormal activation of immune system T lymphocytes and macrophages leading to hemophagocytosis. Currently, the diagnosis of HLH can be established based on a family history of HLH and/or evidence of genetic defects or by satisfying 5 of 8 clinicopathologic criteria. This case-control study aims to examine the extent of hemophagocytosis in the bone marrow examinations of patients satisfying diagnostic criteria for HLH.

Design: Hemophagocytosis in 6 bone marrow aspirates from 3 patients satisfying criteria for HLH was compared with 20 random bone marrow controls. Macrophages with hemophagocytosis were counted in fields containing approximately 9000 nucleated cells by 2 authors using a Miller disc. Unpaired t test was used for statistical analysis.

Results: Mean hemophagocytosis count in the HLH cases was estimated at 0.081717% (range, 0%-0.31%), whereas in the controls the mean hemophagocytosis count was 0.00855% (range, 0%-0.04%). The difference was statistically significant (P = .01). However, there was a large overlap between HLH and control groups.

Conclusions: This study documents that rare hemophagocytosis can be seen in random bone marrow aspirates without clinical diagnosis of HLH. Although the hemophagocytosis counts are significantly higher in HLH than controls, overlap of the counts precludes diagnosis of HLH by morphology alone. This supports the clinical practice of relying on many clinicopathologic criteria. Further studies in different populations are needed to understand the impact of this study.

Pure Red Cell Aplasia in HIV/AIDS Spontaneously Remits After Intravenous Immunoglobulin Therapy

(Poster No. 26)

Cleve O. James, PhD1; Payam Arya, MD2 (payamarya@gmail.com); Lekidelu Taddesse-Heath, MD2; Amy Sitapati, MD1; Wanghai Zhang, MD.2 Departments of 1Internal Medicine and 2Pathology, Howard University Hospital, Washington, DC.

We present a 37-year-old man with HIV/AIDS and a 3-month history of anemia that is refractory to treatment with erythropoietin, iron, and multiple blood transfusions. Complete blood count showed a hemoglobin level of 4.1 g/dL with normal white blood cells, platelets, and mean corpuscular volume. Bone marrow biopsy and aspirate smear revealed markedly hypercellular marrow with nearly 100% cellularity, a myeloid-erythroid ratio greater than 20:1, and marked erythroid hypoplasia with rare erythroid precursors and mature forms. The myeloid and megakaryocytic series were progressively maturing. Evidence of parvovirus infection was not appreciated. The special stains showed adequate iron stores and normal reticulin fiber pattern. On bone marrow analysis, the patient was diagnosed with pure red cell aplasia, a rare variant of aplastic anemia in which erythroid precursors and reticulocytes are selectively absent from the bone marrow but all other cell lineages are functionally present. Pure red cell aplasia has an autoimmune basis in most cases. It is typically treated with corticosteroids or immunosuppressive or cytotoxic drugs. However, treatment with intravenous immunoglobulin therapy represents an attractive alternative because it enhances protection against opportunistic infections without suppressing the host's immune system, and this function is desirable in patients with HIV/AIDS. Intravenous immunoglobulin therapy resulted in an amazing resolution of the anemia and its symptoms within 2 weeks of administration, including amplification of erythroid precursors and metamyelocyte numbers and a marked increase in reticulocyte count by 1 log unit. As late as 1 month after intravenous immunoglobulin therapy, the patient's complete blood counts were within reference range.

Diffuse Follicle Center Lymphomas

(Poster No. 27)

Kelly N. Mizell, MD (kmizell@usouthal.edu); John J. Nelson, MD, MPH; Jacek M. Polski, MD. Department of Pathology, University of South Alabama, Mobile.

Follicular lymphoma is one of the most common non-Hodgkin lymphomas. Follicular lymphomas typically involve lymph nodes, have a nodular growth pattern, and are composed of centrocytes and centroblasts. However, rare cases of lymphomas derived from centrocytes and centroblasts have a diffuse pattern. Such cases are designated as diffuse follicle center lymphoma (DFCL) in the World Health Organization classification. We report 3 cases of DFCL that were recently diagnosed at our institution. The patients' ages ranged from 57 to 83 years. Two patients had orbital masses. One had a spinal tumor with meningeal involvement. The orbital biopsies were small, ranging from 0.6 to 1.5 cm. The spinal tumor resection specimen was relatively large. All cases had involvement of fibrous tissue by a dense lymphoid infiltrate composed of small, variably irregular lymphocytes. The process was diffuse in all cases. Variable numbers of preserved germinal centers were seen in both orbital mass biopsies. The lymphoma cells were positive for CD10, CD20, and Bcl-2 in all cases by flow cytometry or immunoperoxidase stains. Fluorescence in situ hybridization performed on the 2 orbital biopsies and polymerase chain reaction performed on the spinal tumor indicated the presence of BCL2 rearrangements. This small series documents that DFCL can be encountered in extranodal sites, especially in the orbit. DFCL is rare but should be considered in the differential diagnosis when dealing with lymphoid infiltrates in soft tissue. The diffuse nature of these lymphomas makes them a diagnostic challenge. Close attention to the immunophenotype and molecular findings helps to confirm the diagnosis of DFCL.

Evaluation of Peripheral Blood Flow Cytometry as a Screening Tool for Non-Hodgkin Lymphoma

(Poster No. 28)

Tonialatoya Eley, MD (Tonialatoya.Eley@beaumont.edu); Mohammad Alsawah, MD; Jozef Malysz, MD; Vonda Douglas-Nikitin, MD. Department of Clinical Pathology, William Beaumont Hospital, Royal Oak, Mich.

Context: Peripheral blood flow cytometry (PBFC) is an ancillary tool that is of great utility in the diagnosis of non-Hodgkin lymphoma (NHL). However, its use to randomly screen for NHL is often misunderstood. Recommended guidelines for PBFC in screening for NHL have been published, but they are often not observed. We examined the indications for PBFC ordered at our institution to assess their rate of positivity in detecting NHL.

Design: We reviewed 605 PBFC samples analyzed from January to December 2007 using a standard lymphoma panel and recorded the following: indication for PBFC, sex, age, ordering physician, PBFC diagnosis, previous diagnosis, biopsy findings, radiology, complete blood count parameters, and peripheral smear review. The percentage of cases with positive PBFC findings was recorded for each indication and was subdivided in the Table.

Results: A positive result was either a monoclonal B-cell population or an aberrant B-, T-, or NK-cell population. See the Table for the most common reasons for PBFC requests. Overall, 25% of the 605 cases were positive. Eighty-four percent of all cases had accepted medical indications; of these, 26% were positive. Twenty-eight percent of cases had nonaccepted indications; of these, 13% were positive. The highest percentages of positive cases were seen with the accepted medical indications.

Conclusions: Accepted medical indications for PBFC produced the highest yield for diagnoses of NHL. Conversely, the nonaccepted indications yielded a low rate of positive results. Considering the cost of flow cytometric testing, this study confirmed the use of the recommended paradigm of decision making for ordering PBFC.

Histiocytic Sarcoma

(Poster No. 29)

Fadi Habib, MD (fhabib1@hfhs.org); Osama Alassi, MD. Department of Clinical and Anatomic Pathology, Henry Ford Health System, Detroit, Mich.

Histiocytic sarcoma is rare neoplasm characterized by malignant proliferation of cells showing morphologic and immunophenotypic features similar to mature tissue histiocytes. A 76-year-old woman presented with a left groin expansile mass. Magnetic resonance imaging of the abdomen and positron emission tomography scan showed hypermetabolic mediastinal masses encasing the thoracic and descending aorta, as well as masses in both adrenal glands, liver, pancreatic head, and along the left anterior pelvis soft tissues. Left groin mass biopsy revealed epithelioid cells with abundant delicate cytoplasm and foci of spindling. The cells showed malignant nuclear features with frequent mitotic figures, including abnormal forms (Figure 8). Foci of coagulative necrosis were seen. The tumor was positive for vimentin, CD163, and CD10, focally positive for CD68 (KP1), and negative for epithelial markers (keratin cocktail, epithelial membrane antigen, cytokeratin [CK] 7, CK20, CAM 5.2, and CK5/6), muscle markers (myogenin, desmin, and smooth muscle actin), hematolymphoid markers (leukocyte common antigen, BerH2, myeloperoxidase, CD1a, CD21, CD34, and ALK-1), melanocytic markers (S100 and HMB-45), and for mammoglobin and C-kit. T- and B-cell gene rearrangements were negative. The patient was not a candidate for aggressive chemotherapy, and palliative treatment was started. The patient died 6 weeks after the diagnosis. The pathologic diagnosis of histiocytic sarcoma is often challenging and requires histologic, immunohistochemical, andmolecular studies. In our case, we reached the diagnosis of histiocytic sarcoma based on the exclusion of other sarcomas and carcinomas including other members of the histiocytic sarcoma/dendritic cell sarcoma group.

Histopathologic Characterization of 11 Cases of Primary Breast Marginal Zone Lymphoma

(Poster No. 30)

Mohamed E. Salama, MD1 (mohamed.salama@path.utah.edu); Jonathan L. Hecht, MD, PhD2; SaWang, MD3; Monika Pilichowska,MD4; Rajan M. Mariappan, MD, PhD.2 1Department of Pathology, University of Utah/ARUP, Salt Lake City; 2Department of Pathology, Beth Israel Deaconess Medical Center, Boston, Mass; 3Department of Pathology, University of Massachusetts Medical School, Worcester; 4Department of Pathology, Tufts-New England Medical Center, Boston, Mass.

Context: Our independently performed previous studies support the notion that primary breast lymphoma (PBL) is a distinct entity. One subtype, marginal zone lymphoma (MZL), occurring primarily or exclusively in the breast, has interesting features such as bilaterality (2/7 cases in the Stanford series). An in-depth morphologic study of PBL-MZL is lacking.

Design: We morphologically and phenotypically characterized 11 cases of PBL-MZL. Lymphoma involving skin overlying breast was excluded. Lymphoma exclusively involving intramammary nodes was included. Diagnostic criteria included B-cell lymphoproliferation with predominantly small lymphocytes with marginal zone differentiation including monocytoid features and cytoplasmic clearing. All cases were CD5/CD10 negative. Parameters evaluated included presence of nodal versus extranodal disease, architectural patterns, and epithelial involvement versus parenchymal involvement. Cases with epithelial involvement were evaluated for ductal or lobular epithelial involvement. Information regarding demographics and antigenic profile were collected from patient charts.

Results: This study included 1 man and 10 women. Age ranged from 31 to 78 years (mean, 59.2 years). Morphologic features identified were as follows: PBL-MZL is predominantly an extranodal disease with only 2 of 11 cases primarily intramammary nodal MZL. Lymphoepithelial lesions were seen in 5 of 11 cases. All 5 cases with epithelial involvement were predominantly terminal ductal-centric. Most cases involved atrophic breast tissue. CD43 immunohistochemical staining was performed on 4 of 11 cases, and coexpression was noted in 3 (75%).

Conclusions: PBL-MZL, unlike ocular or MALT type MZL, is mainly a parenchymal disease. Epithelial involvement, when present, is predominantly around terminal ducts with lymphoepithelial lesions. CD43 is frequently coexpressed.

Relapsed Acute Myelogenous Leukemia Presenting as Histiocytic Sarcoma

(Poster No. 31)

Phillip E. Starshak, MD1 (phillip.starshak@ucdmc.ucdavis.edu); Carol Richman, MD1; Maxwell Fung, MD1; Kavita S. Reddy, MD2; Denis Dwyre, MD.1 1Department of Pathology, University of California Davis Medical Center, Sacramento; 2Department of Molecular Pathology, Genzyme Genetics, New York, NY.

Histiocytic sarcoma is a rare malignancy with a poor prognosis and presents as nodal or extranodal tumors with a predilection for the skin and gastrointestinal tract. These tumors are of histiocytic origin with only a few case reports documenting an association with acute myelogenous leukemia (AML). We report a case of a 33-year-old woman who presented 2 years prior with AML with monocytic antigen expression and a rearrangement involving the MLL gene (11q23). The patient was treated with multiagent chemotherapy followed by stem cell transplant from a male sibling. After 18 months of clinical remission, the patient presented with multiple subcutaneous nodules. Hematoxylin-eosin-stained slides of the nodules along with immunohistochemical stains were consistent with histiocytic sarcoma. Fluorescence in situ hybridization using a MLL breakapart probe (Abbott Molecular Inc) and a Y probe on paraffin-embedded tissue showed a MLL gene rearrangement with absence of a Y signal in ~78% of interphases and normal MLL signals with the presence of a Y signal in ~20% of interphases. Cytogenetics confirmed these findings (46,XX with MLL rearrangement). Concurrent bone marrow biopsy showed no evidence of relapse by histologic and flow cytometry analysis. Cytogenetics of the bone marrow was 46,XY (100% donor origin). This represents a unique case of relapsed AML presenting solely as histiocytic sarcoma. It suggests that leukemic stem cells survive in microenvironments outside the bone marrow. The presence of a MLL rearrangement in both the acute monoblastic leukemia and subsequent histiocytic sarcoma provided the evolutionary link.

CD5^sup -^/CD23^sup +^ Primary Splenic Mantle Cell Lymphoma: A Mimic of Splenic Marginal Zone Lymphoma

(Poster No. 32)

John M. Childs, MD (john.childs@duke.edu); Elizabeth N. Pavlisko, MD; Barbara K. Goodman, PhD; Anand S. Lagoo, MD, PhD. Department of Pathology, Duke University Medical Center, Durham, NC.

Primary splenic mantle cell lymphoma is uncommon and the characteristic CD5^sup +^/CD23^sup -^ immunophenotype of mantle cell lymphoma is usually present. We report a case of a CD5^sup -^/CD23^sup +^ splenic mantle cell lymphoma in a 54-year-old man who presented with epigastric pain and massive splenomegaly. A computed tomography scan showed minimal abdominal and retroperitoneal lymphadenopathy. His blood count was significant for anemia and thrombocytopenia. Flow cytometric immunophenotyping of peripheral blood demonstrated a κ-restricted monoclonal B-cell population constituting 14% of total white cells that expressed CD19, CD20, CD22, CD25 (dim), and CD23, but did not express CD5, CD10, or CD103. A bone marrow biopsy showed 10% involvement by an immunophenotypically similar process. The primary differential diagnosis was splenic marginal zone lymphoma, and subsequently splenectomy was performed for confirmation. The spleen revealed white pulp expansion by monocytoid B cells with an immunophenotype similar to that in the blood and marrow, leading to a diagnosis of splenic marginal zone lymphoma. Subsequent single agent treatment with Fludarabine for worsening lymphadenopathy was followed by pancytopenia. A repeat bone marrow biopsy found extensive involvement by lymphoma, raising doubts about the initial diagnosis. A cyclin D1 stain was performed on the marrow and was found to be positive. The lymphoma in the splenectomy specimen also proved to be cyclin D1 positive. Despite additional treatment, the patient died approximately 14 months after diagnosis. CD5-negative primary splenic mantle cell lymphoma can closely mimic splenic marginal zone lymphoma and pose a significant diagnostic challenge.

C-myc Gene Rearrangement in a Case of B-Cell Lymphoproliferative Disorder With Prolymphocytic Morphology

(Poster No. 33)

Shourong Zhao, MD1 (shourongz@yahoo.com); Phillip Cason, MT(ASCP)1; Andrew Pippas, MD.2 Departments of 1Pathology and 2Medical Oncology, Columbus Regional Healthcare System, Columbus, Ga.

A 55-year-old man presented with fatigue, headaches, nausea, and gingival bleeding. His complete blood cell count showed a white blood cell count of 205 000/µL, a platelet count of 79 103/µL, and a hemoglobin level of 11.3 g/dL. His examination revealed enlarged peripheral adenopathy and dramatic splenomegaly. Peripheral blood smear demonstrated increased medium-sized lymphocytes with open nuclear chromatin, prominent nucleoli, and abundant basophilic cytoplasm. Themorphologic features were consistent with prolymphocytes. Bone marrow biopsy (aspirate not obtained) showed hypercellularity (80%-90%) with diffuse interstitial infiltration of lymphocytes. Immunophenotype revealed a monoclonal B-cell population that was positive for CD19, CD20, CD22, CD45, FMC-7, κ surface light chain, and immunoglobulin (Ig) G; it was negative for CD2, CD3, CD4, CD5, CD7, CD8, CD10, CD13, CD14, CD23, CD38, CD56, CD34, CD11c, and CD103. Immunohistochemical stains on the biopsy were negative for cyclin D1, DBA-44, and Bcl-6, while positive for BCL-2. There was no detectable signal for Ki-67. Cytogenetics and fluorescence in situ hybridization were positive for t(8;14)(q24.1;q32) in 19 of the 20 metaphases. No evidence of t(11;14), trisomy 11, or other abnormalities was detected. A diagnosis of B-cell lymphoproliferative disorder with c-myc translocation and prolymphocytic features was made and also confirmed by consultation with M. D. Anderson Cancer Center. Subsequent treatment with rituximab, fludarabine, and cyclophosphamide (FCR) achieved a complete clinical response. The patient continues on treatment and molecular response will be assessed on completion of 6 cycles of FCR.

Hepatosplenic T-Cell Lymphoma Diagnosed at Autopsy

(Poster No. 34)

Edward T. Jones, MD (ned-jones@hotmail.com); Lizardo Cerezo, MD; Julia Martin, MD. Department of Pathology, Orlando RegionalHealthcare, Orlando, Fla.

Hepatosplenic T-cell lymphoma is a rare, aggressive extranodal lymphoma affecting the liver, spleen, and bone marrow. At presentation, patients characteristically have cytopenias, hepatosplenomegaly, elevated serum lactate dehydrogenase, and B-type symptoms. We report a case of hepatosplenic T-cell lymphoma diagnosed at autopsy after late presentation and precipitous clinical decline. A 38-year-old man with no significant medical history presented to an outside hospital with a 2-month history of flulike symptoms and worsening edema. Initial findings included anemia, thrombocytopenia, elevated lactate dehydrogenase, hypoalbuminemia, anasarca, bilateral pleural effusions, and splenomegaly. Bone marrow examination revealed moderate hypercellularity with moderate granulocyte hyperplasia, left shift, and increased megakaryocytes. Flow cytometry was suggestive of left shift in myeloid maturation. Despite treatment for presumed sepsis, the patient quickly developed respiratory failure and hypotension and was transferred to our hospital in multisystem organ failure. Findings at autopsy included hepatomegaly (2877 g), splenomegaly (434 g) with diffuse infarct, ascites, and pulmonary edema. Atypical, enlarged lymphocytes were present in the spleen and sinusoids of the liver but not in the bone marrow. Malignant cells were also found in blood vessels of the kidneys, adrenal glands, and pancreas. By immunohistochemistry, the malignant cells expressed CD3, TIA-1, and perforin. The cells did not express CD4, CD5, CD8, CD20, CD56, CD68, or CD117. No TIA-1- or perforin-positive cells were present in the bone marrow. Findings that make this case unusual include postmortem diagnosis, rapidity of progression, absence of bone marrow involvement, and positivity for perforin in the malignant cells.

A Rare Case of Amyloidosis Involving Bone Marrow and Associated With Bleeding Disorder and Factor IX Deficiency

(Poster No. 35)

Andrew Pippas, MD1 (andrew.pippas@crhs.net); Debora Probst, HT(ASCP)2; Alan Clepper, MD2; Shourong Zhao, MD.2 Departments of 1Medical Oncology and 2Pathology, Columbus Regional Healthcare System, Columbus, Ga.

Bone marrow involvement with amyloidosis may be seen in both primary and secondary amyloidosis such as systemic amyloidosis, plasma cell dyscrasia, and chronic inflammatory disease. Amyloidosis associated with coagulopathy results from abnormal vessel wall integrity, plasma components that inhibit fibrin formation, and depletion of clotting factors by amyloid, specifically factor X. It is well known that protease Nexin-2/amyloid β protein precursor is a tight binding inhibitor of coagulation factor IX. We report a rare case of a 52-year-old woman who presented with gingival bleeding following dental extraction with prolonged prothrombin time and activated partial thromboplastin time, and hypofibrinogenemia secondary to α2-antiplasmin deficiency. Factor assays revealed a diminished factor IX level (40%). Mixing studies did not show an inhibitor. Her bone marrow demonstrated normal hematopoiesis with diffuse amyloidosis, which was confirmed by Congo red stain. She was treated with Lovenox and aminocaproic acid for fibrinolysis and thalidomide/dexamethasone initially; factor IX levels, however, remained diminished. She then underwent an autologous bone marrow transplant complicated with severe hypofibrinogenemia and subnormal factor IX levels. To directly demonstrate that amyloidosis specifically attracts and interacts with factor IX, a specific antibody for factor IX was used for immunohistochemical stain. The stain showed diffuse strong positivity of factor IX within the amyloidosis. This result suggests that amyloid protein is able to bind specific coagulation factors such as factor IX and can be demonstrated by immunohistochemical stain using specific antibody, and further confirms that amyloid β protein precursor acts as a binding inhibitor of factor IX.

Aplastic Anemia With Concomitant Systemic Mastocytosis: First Reported Case

(Poster No. 36)

Jacob E. Sramek, MD (jacobsramek@centura.org); Jerome B. Myers, MD, PhD. Department of Pathology, Penrose-St Francis Health Services, Colorado Springs, Colo.

Aplastic anemia is characterized by multilineage cytopenias and bone marrow hypoplasia. In this process, mast cells are spared or increased in number. However, reported cases of mastocytosis in the setting of aplastic anemia have lacked the diagnostic features of clonal mast cell proliferation. We report the first documented case of aplastic anemia and systemic mastocytosis occurring concomitantly. A previously healthy 48-year-old man presented with a petechial rash, epistaxis, and fever. A complete blood count at the time of admission showed a platelet count of 11 000/µL, a neutrophil count of less than 50/µL, and a hemoglobin level of 12.0 g/dL with 0.1% reticulocytes. A bone marrow biopsy demonstrated trilineage hypoplasia with a 5% overall cellularity. The biopsy additionally showed 2 compact mast cell aggregates of greater than 15 cells each. These mast cells displayed an atypical, spindled morphology (Figure 9) and were strongly positive for CD25 by immunohistochemistry. Themultifocal aggregates showing spindled morphology and CD25 expression fulfill the diagnostic criteria for systemic mastocytosis. Systemic mastocytosis can present with cytopenias; however, overt marrow failure only occurs secondary to extensive bone marrow infiltration or fibrosis. In the present case, the mast cell aggregates were sparse and found in a background of classic aplastic anemia. The significance of these 2 processes occurring concomitantly is unclear. However, the present case serves to illustrate that mastocytosis in the setting of aplastic anemia may represent a clonal mast cell process in rare cases.

Spontaneous Splenic Rupture Complicating Primary Treatment Refractory Burkitt Lymphoma

(Poster No. 37)

Archana M. Agarwal, MD1 (archana.agarwal@hsc.utah.edu); Hwee Lim, MD2,3; Neeraj Agarwal, MD2; Martha Glenn, MD.2,3 Departments of 1Pathology, 2Internal Medicine, and 3Hematology, University of Utah, Salt Lake City.

Burkitt lymphoma is a high-grade B-cell malignancy. Spontaneous rupture of spleen in association with Burkitt lymphoma has been reported only once in the literature. We describe a case of primary treatment refractory Burkitt lymphoma whose disease course was complicated by spontaneous rupture of spleen. A 35-year-old man presented with cervical lymphadenopathy. Four months earlier, he was diagnosed with Burkitt lymphoma, which went into remission with 4 cycles of chemotherapy. Lymph node biopsy revealed recurrent Burkitt lymphoma. Laboratory studies revealed white blood cell count (WBC), 64 000/µL; hematocrit, 29%; platelet, 29 000/µL; lactate dehydrogenase (LDH), 83 997 U/L; and uric acid, 69 mg/dL. Bone marrow showed predominantly atypical malignant-appearing lymphocytes with smudged chromatin and cytoplasmic vacuolation. Salvage chemotherapy was started. On the third day, he developed abdominal fullness with transfusion refractory anemia. Exploratory laparotomy revealed a splenic laceration. With a diagnosis of spontaneous splenic rupture, splenectomy was performed. Burkitt lymphoma was diagnosed on the sections of the spleen by histology and by immunohistochemistry. Salvage chemotherapy was reinstituted after a week. However, 10 days after completion of the first cycle of salvage chemotherapy, peripheral blood smear revealed predominance of large atypical lymphocytic cells consistent with lymphoma cells with a WBC count of 13 780/µL and LDH of 17 539 U/L. The patient died 4 weeks after the presentation. Spontaneous splenic rupture signifies an aggressive disease. Symptoms can vary from abdominal pain to fullness to transfusion refractory anemia. We will review the literature on spontaneous splenic rupture in aggressive hematologic malignancies with emphasis on Burkitt lymphoma.

Composite Follicular Lymphoma and Chronic Lymphocytic Lymphoma

(Poster No. 38)

Archana M. Agarwal, MD1 (archana.agarwal@hsc.utah.edu); K. Reichard, MD2; Mohamed E. Salama, MD.1 1Department of Hematopathology, University of Utah, Salt Lake City; 2Department of Hematopathology,University of New Mexico, Albuquerque.

Low-grade B-cell lymphomas comprise several well-defined, clinically and immunophenotypically distinct clinical entities. Composite lymphomas are a rare occurrence of 2 different types of lymphoma at the same anatomic site. These cases may pose major biologic, diagnostic, and therapeutic dilemmas. We describe a case of composite low-grade B-cell non-Hodgkin lymphoma involving the supraclavicular lymph node. Histopathologic and comprehensive immunophenotypic analyses were performed using the following antibodies: CD20, CD10, MIB-1, CD3, CD5, CD43, BCL-2, and BCL-6. To ascertain that it represents a coincidental occurrence of 2 unrelated lymphomas or possible origin from a common precursor B cell (ie, different phases of clonal evolution), we used fluorescence in situ hybridization probes for 11q22.3(ATMx2), 12cen(D12Z3x2), 13q14(RB1x2), 13q14.3(D13S25x2),17p13.1(TP53x2), and IGH/CCND1-XT (Vysis, Des Plaines, Ill). A 78-year-old man presented with a left supraclavicular lymphadenopathy. A lymph node biopsy showed complete effacement of the architecture with neoplastic follicles and a monotonous population of small lymphocytes in the interfollicular area. The neoplastic follicles are variably sized and were composed of small cleaved cells with less than 5 centroblasts per high-power field. They showed strong positivity for CD20, C10, and BCL-2 while the interfollicular small lymphocytes showed dim CD20, with coexpression of CD5. Results of fluorescence in situ hybridization studies are pending. We describe a case of composite lymphoma with both follicular lymphoma and chronic lymphocytic lymphoma components. An expanded immunohistochemical panel can delineate each of the components. The identification of both components has significant management implications.

Acute Myeloid Leukemia With Complex Cytogenetics Presenting as a Mediastinal Mass

(Poster No. 39)

Sonali P. Ayar, MD1 (sayar@usouthal.edu); Hamayun Imran,MD, MSc2; Skip Haines, CLSpCG3; Andrea G. Kahn, MD1; Jacek Polski, MD.1 Departments of 1Pathology and 2Pediatric Hematology/Oncology,University of South Alabama, Mobile; 3Department of Pathology, Tricore Reference Laboratories, University of New Mexico, Albuquerque.

Myeloid sarcoma localized to mediastinum with superior vena cava syndrome is an exceptionally rare manifestation of acute myeloid leukemia (AML). About 19 cases of mediastinal myeloid sarcoma have been reported in the literature.We report the case of a 2-year-old AfricanAmerican boy who presented with superior vena cava syndrome and respiratory failure. On radiographic studies, he was found to have a right neck mass that extended into mediastinum with multiple cervical and supraclavicular lymphadenopathy and pericardial effusion. Rare circulating blasts were identified. Flow cytometry of peripheral blood revealed variable expression of myelomonocytic markers in blasts. The bone marrow biopsy and aspiration revealed acute myeloid leukemia with blasts positive for myeloperoxide and butyrate esterase. The conventional cytogenetic chromosome and fluorescence in situ hybridization analysis revealed complex abnormalities from 2 related abnormal cell lines including trisomy 4, 6, 13, 18, and 19, loss of chromosome 8, 2 copies of an additional dicentric derivative chromosome der(1;8)t(1;8)(p13;q24), and derivative chromosome 10 involved in translocation t(10;11)(p12;q21). The patient received induction chemotherapy as per COG AAML0531 protocol. The follow-up bone marrow biopsy and aspiration at day 28 documented remission. On repeat radiologic studies, a stable mediastinal mass was identified with reduced density. A review of the literature shows that complex chromosomal abnormalities and poor long-term prognosis were previously reported in mediastinal myeloid sarcoma. This case documents presence of a complex karyotype associated with AML with a mediastinal mass. This represents a rare but distinct subset of AMLs that require prompt diagnosis and intensive treatment.

A Case of Anorectal Plasmablastic Lymphoma in an HIV-Positive Patient

(Poster No. 40)

Lichao Zhao, MD, PhD1 (LichaoλZhao@hotmail.com); William F. Kern, MD1; Gregory N. Fuller, MD, PhD2; Jian Yi Li, MD, PhD3; S. T. Dunn, PhD1; Arafat Tfayli, MD4; Ronald Squires, MD5; Kar-Ming Fung, MD, PhD.1 Departments of 1Pathology, 4Medicine Hematology/Oncology, and 5Surgery, University of Oklahoma Health Sciences Center, Oklahoma City; 2Department of Pathology, The University of TexasM. D. Anderson Cancer Center, Houston; 3Department of Pathology, The Methodist Hospital, Houston, Tex.

Plasmablastic lymphoma (PBL) is a recently described and uncommon HIV-related lymphoma, classified as "plasmablastic lymphoma of the oral cavity" under the current World Health Organization classification. However, extraoral involvement has been increasingly recognized. Diagnosis of plasmablastic lymphoma may be challenging to pathologists due to its relatively rare occurrence and unusual immunophenotype. We present a case that occurred in the anus. A 39-year-old man with 13-year history of HIV presented with painful perianal ulceration for 4 months. Examination revealed a mass located in the anal canal with perianal extension. Microscopically, the biopsy specimens were dominated by large, anaplastic, and plasmacytoid cells with vesicular nuclei. Mitoses were common. The tumor cells had moderate amount of basophilic cytoplasm with both central and eccentrically located large nuclei with large nucleoli and a paranuclear halo in some but not all tumor cells. Multinucleated tumor cells were not readily seen. Immunophenotypically, the tumor cells were negative for leukocyte common antigen, CD20, CD3, and ALK, but focally (25%) positive for CD138 (Figure 10) and epithelial membrane antigen. B-cell lineage of this tumor was confirmed by clonal immunoglobulin heavy chain rearrangement detected through molecular analysis. The morphologic, immunophenotypic, and molecular features are consistent with a diagnosis of PBL. The association of PBL with human herpesvirus 8 (HHV-8) is controversial. In this case, HHV-8 antigen was not detected in the tumor cells by immunohistochemistry. The patient responded well to the first round of chemotherapy (EPOCH protocol: etoposide, vincristine, doxorubicin, cyclophosphamide, and prednisone) with significant decrease of perianal pain at 2-month follow-up.

Nodal Marginal Zone B-Cell Lymphoma Presenting With Unilateral Lymphedema: A Case Report and Review of the Literature

(Poster No. 41)

Jolie R. Rodriguez, MD (jolierodriguez@bellsouth.net); Jacek M. Polski, MD. Department of Pathology, University of South Alabama, Mobile.

Nodal marginal zone B-cell lymphoma is considered a distinct type of marginal zone lymphoma (MZL) in the World Health Organization classification. Current literature describes nodal MZL as an indolent disease in patients with a mean age of 60 years. These patients typically present with lymphadenopathy and disseminated disease. Cases of nodal MZL have also been described in children and young adults, in whom the average patient is an adolescent boy presenting with localized disease.We report the unusual case of a 24-year-old woman presenting with unilateral lower extremity lymphedema and diffuse lymphadenopathy; splenomegaly was not identified. Biopsy of a 4-cm axillary lymph node revealed a proliferation of mostly small lymphocytes admixed with rare immunoblasts and plasma cells; occasional poorly defined germinal centers were seen. Of interest, many of the sinuses were distended with edematous fluid. Flow cytometric study documented a monoclonal B-cell process with an immunophenotype consistent with MZL. Cytogenetics studies revealed no abnormalities. Although neoplasms may appear in a clinical setting of lymphedema, only very rare case reports of non-Hodgkin lymphomas associated with lymphedema exist. To our knowledge, this is the first reported case of nodal MZL presenting with lymphedema.

Composite Lymphoma Involving the Bone Marrow and Presenting as Pancytopenia and Myelofibrosis

(Poster No. 42)

Archana M. Agarwal, MD (archana.agarwal@hsc.utah.edu);Mohamed E. Salama, MD. Department of Pathology, University of Utah, Salt Lake City.

Composite lymphoma constitutes the presence of 2 different types of Hodgkin and non-Hodgkin lymphoma at the same anatomic site. We describe a case of composite mantle cell lymphoma and Hodgkin lymphoma with unusual presentation. Comprehensive immunophenotypic analyses were performed using a panel of antibodies. Reticulin stain for fibrosis, and in situ hybridization studies for Epstein-Barr virus-encoded RNA (EBER-1) were performed on the bone marrow core biopsy. Fluorescence in situ hybridization (FISH) study for t(11;14) using a SpectrumGreenlabeled IgH probe and a SpectrumOrange-labeled CCND1/MYEOV probe was performed on the peripheral blood. A 72-year-old man presented with pancytopenia. The bone marrow (BM) core biopsy showed marked fibrosis (4^sup +^) and many large atypical Reed-Sternberg-like cells in a polymorphic background that expressed CD30 and weak CD15. CD20 and cyclin D1 highlighted scattered small lymphoid cell population. Subsequent computed tomography scans identified a retroperitoneal lymph node (LN) with an identical morphology to that of the BM. Flow cytometric analysis performed on the whole blood, BM, and LN showed small CD5^sup +^, CD10^sup -^ κ-restricted B-cell population. FISH study performed on the whole blood revealed 4.4% of the cells that were positive for the t(11;14). We describe a case of composite mantle cell and Hodgkin lymphoma with unusual presentation of pancytopenia and myelofibrosis in which both components are intermixed in 2 separate anatomical sites. Identification of both components has significant management implications.

Correlation of Pathologic Grading, Ki-67 Expression, and Fluorine-18 2-Fluoro-2-Deoxy-D-Glucose-Positron Emission Tomography Results With Bone Marrow and Splenic Involvement in Patients With Follicular Lymphoma

(Poster No. 43)

Jozef Malysz, MD1 (jm23777@hotmail.com); A. M. Blenc, MD1; M. D. Smith, MD1; B. Tang, MD2; O. C. Wong, MD2; R. P. Zekman, DO3; B. Ravipati, MD3; I. Jaiyesimi, DO3; V. K. Douglas-Nikitin,MD.1 Departments of 1Clinical Pathology, 2Nuclear Medicine, and 3Medical Oncology,William Beaumont Hospital, Royal Oak, Mich.

Context: Clinical variability in patients with follicular lymphoma (FL) inspires the search for characteristics to stratify patients into predictable subgroups. Pathologic grading (PG) is based on morphology, and Ki-67 indicates "aggressiveness" but is not used in grading. Follicular Lymphoma International Prognostic Index (FLIPI) considers clinical parameters to predict response. Fluorine-18 2-fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET) scanning is used to stage lymphomas. We evaluated PG and Ki-67 expression compared with FDG-PET and FLIPI score (FS).

Design: We evaluated 23 patients with pretreatment FDG-PET. PG and Ki-67 were evaluated by 2 hematopathologists, and the correlation coefficient was calculated. Results were correlated with FDG-PET standard uptake value (SUV) and FS. Bone marrow involvement (BMI) was defined by heterogeneous FDG uptake with histopathologic correlation. Splenic involvement (SI) was defined as splenic uptake higher than the liver. Discriminant analysis was performed for BMI and SI against the independent variables BmSUV and BxSUV.

Results: Interobserver correlation for PG revealed no difference (P = .80) with the weighted κ coefficient of 0.80 and a coefficient interval of 0.62 to 0.99, both indicating agreement between the readers. PG was significantly correlated with Ki-67 expression (P < .01). Ki-67, BmSUV, and FS were highest in PG 3 (P < .001). BmSUV and BxSUV correctly classified BMI with 78% and 74% accuracy, but BmSUV predicted better than BxSUV in SI at 78% and 65%, respectively. There were no such predictions by PG, Ki-67, or FS.

Conclusions: Ki-67 expression correlates with PG and is significantly higher in grade 3 than in grades 1/2 FL. BmSUV predicts BMI and SI with highest values in grade 3 FL.

Morphologic Spectrum of Non-Burkitt Lymphomas in MYC-Associated Cytogenetic Abnormalities

(Poster No. 44)

Shree G. Sharma, MD (drshreegopal@gmail.com); Jeffrey Sawyer, PhD; William T. Bellamy, RPh, PhD; Robert Lorsbach, MD, PhD; Krishna Oza, MD; Zeba N. Singh, MD. Department of Pathology, University of Arkansas for Medical Sciences, Little Rock.

Context: Chromosomal translocations involving MYC [t(8;14), t(8;22), t(2;8)] are characteristically associated with Burkitt lymphoma (BL). Alterations targeting MYC can also be detected in other lymphomas. The present study aims to evaluate the spectrum of lymphomas associated with MYC aberrations and to determine if BL-like morphology is a surrogate of MYC aberration.

Design: The cytogenetic and molecular laboratory data bases of the University of Arkansas for Medical Sciences were searched for cases within the following diagnostic group during the last 5 years: (1) abnormalities involving 8q24 region without recurrent abnormalities and (2) cases with additional recurrent abnormality(ies). Cases with classic BL abnormality [t(8;14), t(8;22), t(2;8)] were excluded.Morphologic and immunophenotypic features were reviewed blinded to the original diagnosis and the specific chromosomal abnormality.

Results: The search resulted in 13 cases. The Table shows the distribution of cases. The samples studied included fine-needle aspiration (3), bone marrow (5), lymph node biopsy (3), and soft tissue biopsy (2).

Conclusions: Eight (61.5%) cases were intermediate to high grade, while 5 (38.5%) cases were low grade. Classic BL-like morphology was absent in either additional recurrent translocations or complex translocations. Synchronous or sequential acquisition of MYC abnormality, with respect to other recurrent translocations, may determine the aggressive morphology/behavior; in cases with increased copy numbers of MYC, the number of extra copies may be the trigger. Comparison with classic BL and detailed morphologic and immunophenotypic evaluation by fluorescence in situ hybridization to confirm breakpoints in complex translocations and to investigate MYC copy number is planned.

Classic Hodgkin Lymphoma in a 5-Year-Old Girl

(Poster No. 45)

Luis Brandi, MD (luis.brandi@ttuhsc.edu); Safaa Labib, MD; Viviane Mamlock, MD; Anthony Cecalupo, MD. Department of Pathology, Texas Tech Health Sciences Center, Lubbock.

Hodgkin lymphoma (HL) in a 5-year-old is an extremely rare presentation as substantiated by literature review. For children 5 years and younger, the incidence of HL is 0.3 per 100 000. HL is a malignant lymphoma that has a bimodal distribution with regard to age, with an early peak occurring between ages 15 to 35 years and with a second peak late in life. A 5-year-old Hispanic girl who presented with complaints of vague abdominal pain was noted to have a mediastinal mass on chest radiograph. Her computed tomography scan and magnetic resonance imaging of the neck, abdomen, and pelvis were negative. The gallium scan was positive in the chest. Skeletal survey and bone scan were negative. Laboratory findings showed an increased erythrocyte sedimentation rate and C-reactive protein. Computed tomography-guided needle biopsy of the mediastinal mass revealed a granulomatous inflammation with eosinophils, plasma cells, and occasional large atypical cells with prominent nucleoli. These morphologic findings were suspicious for HL. A subsequent excisional biopsy of the mass, via a video-assisted right thoracotomy, revealed mostly mature lymphocytes admixed with eosinophils, plasma cells, and typical Reed-Sternberg cells. Mononuclear variants and mummified cells were also noted. Immunohistochemical stains showed a membranous and Golgi staining pattern for CD30 and CD15 by the Reed-Sternberg cells. No bone marrow involvement by the HL was diagnosed. Although exceedingly rare, it is important to entertain the possibility of HL occurring much earlier than the first peak of the bimodal distribution.

A Leukemic Presentation of CD4^sup +^/CD56^sup +^ Hematodermic Neoplasm

(Poster No. 46)

Karimireddy J. Reddy, MD (karimireddy.reddy@ucdmc.ucdavis.edu); Elena Nedelcu, MD; Carol Marshall, MD. Department of Pathology, University of California Davis Medical Center, Sacramento.

CD4^sup +^/CD56^sup +^ hematodermic neoplasm, formerly known as blastic CD4^sup +^ natural killer cell lymphoma, is a rare neoplasm that commonly presents with skin lesions and spreads rapidly to other sites. Overall prognosis is dismal, with a median survival rate of 14 months. The plasmacytoid dendritic cell has recently been demonstrated as the cell of origin. The malignant cells have a blastic morphology, expressing CD4, CD56, CD43, and CD123 and showing no T-cell receptor gene rearrangement. We report an unusual leukemic presentation of CD4^sup +^/CD56^sup +^ hematodermic neoplasm. A 70-year-old man presented with isolated thrombocytopenia. He had no cutaneous involvement at presentation but developed skin lesions 5 months later. A bone marrow biopsy showed extensive infiltration of the marrow by a monotonous population of atypical cells with a blastic morphology. Flow cytometry performed on the marrow showed CD4^sup +^/CD56^sup +^ cells comprising 53% of the total cells. Skin biopsies demonstrated diffuse dermal infiltration, with cells showing similar morphology and immunophenotype and no T-cell gene rearrangement. Our patient is currently responding well to chemotherapy with resolution of skin lesions. Because CD4^sup +^/CD56^sup +^ hematodermic neoplasm is an aggressive disease with a rapid downhill course, early recognition and proper diagnosis is critical and requires a high degree of suspicion. Specific dendritic cell markers, such as CD123 and BDCA-2, are also valuable tools in diagnosis. Our case also highlights the importance of bone marrow biopsy in unexplained isolated thrombocytopenia, because accurate pathologic diagnosis of this aggressive entity is essential for treatment.

Polyclonal Plasma Cells Do Not Exclude a Diagnosis of Primary Cutaneous Marginal Zone Lymphoma

(Poster No. 47)

Guang Fan, MD, PhD (fang@ohsu.edu); David Gray, MD. Department of Pathology, Oregon Health and Science University, Portland.

Context: The World Health Organization-European Organization for Research and Treatment of Cancer classification of cutaneous lymphomas establishes the primary cutaneous marginal zone lymphoma as an indolent lymphoma composed of small marginal zone B cells, lymphoplasmacytoid cells, and plasma cells. The plasma cells are commonly reported to have monotypic cytoplasmic immunoglobulin light chain expression on paraffin sections. Here we report one institution's experience with the frequency of monoclonal plasma cell population in primary cutaneous marginal zone lymphoma using immunohistochemistry and in situ hybridization.

Design: A Powerpath database from our institution was searched (January 2000-December 2007) to identify cases of primary cutaneous marginal zone lymphoma. The authors reviewed the cases.

Results: The database search yielded 22 marginal zone lymphoma cases. κ/λ light chain immunohistochemistry or in situ hybridization was performed in 18 cases. Monoclonal plasma cell population was found in 83% (15/18) of the cases (10 by in situ hybridization and 5 by immunohistochemistry). Polyclonal plasma cells were found in 2 cases by in situ hybridization. Clonality could not be determined in 1 case. In 2 cases with polyclonal plasma cells, IGH rearrangements were tested by polymerase chain reaction, and monoclonal B-cell population was identified.

Conclusions: When evaluating a skin biopsy for marginal zone lymphoma, plasma cell clonality is a useful feature in differentiating between reactive and neoplastic conditions. However, polyclonal plasma cells could be seen in about 10% of the cases. In the presence of suspicious morphologic features with polyclonal plasma cells, molecular studies for IGH gene rearrangement can help in equivocal cases.

POSTER SESSION 200: THURSDAY, SEPTEMBER 25, 2008, 1:30 PM-4:00 PM

Gastrointestinal and Liver Pathology; Molecular Pathology

Prevalence and Significance of Non-Viral-Related Pathologic Findings in Needle Biopsies for Chronic Viral Hepatitis

(Poster No. 1)

Vidhya Nair, MBBS, MD (vidhya.nair@utoronto.ca); Sandra Elizabeth Fischer, MD; Oyedele Adeyi, MD. Department of Pathology, Toronto General Hospital/University Health Network, University of Toronto, Toronto, Ontario.

Context: Liver biopsy remains a useful tool in the management of chronic viral hepatitis. It is not uncommon for the pathologist to detect other pathologic processes during the evaluation. This study was done to define the scope and frequency of some unexpected but significant new findings in patients biopsied for chronic viral hepatitis types B and C.

Design: All of the liver biopsy cases with a diagnosis of viral hepatitis type B or C from the past 6 years (July 2001-July 2007) at the University Health Network were reviewed. The patient demographics and the degree of viral hepatitis-related changes were documented. Other nonviral hepatitis-related findings were defined and analyzed.

Results: A total of 1842 liver needle biopsies were performed in the evaluation of viral hepatitis types B and C. The ages ranged from 15 to 80 years. A second diagnosis was found in 410 (22.26%) cases as follows: 58 (3.15%) hepatocellular carcinoma, 16 dysplastic nodules, 7 granulomatous disease, 4 drug-induced hepatitis, 2 Wilson disease, 2 metastasis, 1 cholangiocarcinoma, 3 primary biliary cirrhosis, 1 chronic lymphocytic leukemia, 1 α-antitrypsin, 1 cystic fibrosis, and 1 schistosomiasis. Also noted were 135 (7.33%) steatosis, 116 (6.3%) steatohepatitis, and 62 (3.37%) hemosiderosis.

Conclusions: Liver biopsies for chronic viral hepatitis revealed additional pathologic processes in 22.26% of cases. Many of the processes needed significant therapeutic intervention or change in previously planned therapy. The role of the pathologist in actively looking for such changes in the evaluation of the liver needle biopsy is emphasized.

Colorectal Polyps Often Harbor Additional Diagnoses

(Poster No. 2)

Shefali Chopra, MD (chopras@uci.edu); Mark Li-Cheng Wu, MD. Department of Pathology, University of California, Irvine Medical Center, Orange.

Context: Specimens from biopsies of suspected colorectal polyps are among the most frequently examined specimens for surgical pathologists. The majority of these specimens show traditional adenomas, serrated polyps, or normal mucosa, which generally are easily and rapidly diagnosed at low magnification. Consequently, pathologists are tempted to examine these specimens quickly and only at low magnification, assuming these specimens will harbor only polyps or normal mucosa, and pathologists may refrain from examining these specimens further at high magnification once polyps are diagnosed. However, in addition to polyps, directed review might reveal other diagnoses that are easily overlooked at low magnification.

Design: We retrospectively reviewed 100 specimens from biopsies of suspected colorectal polyps, for which polyps were diagnosed, to determine the frequency of other diagnoses in addition to polyps.

Results: In addition to polyps, 17 (17%) of 100 specimens contained other diagnoses. These diagnoses included the following: 2 schistosomiasis (Figure 11), 1 intestinal spirochetosis, 5 mucosal prolapse, 6melanosis coli, 2 lymphocytic colitis, and 1 eosinophilic colitis. These other diagnoses often affected parts of the mucosa that were spared by the polyps or that were evident only at high magnification. Melanosis coli was the diagnosis most commonly overlooked by the original pathologists.

Conclusions: Specimens from biopsies of colorectal polyps often contain other diagnoses in addition to polyps, and these other diagnoses can be clinically significant. Directed review, examination at high magnification, and examination of parts of the mucosa spared by the polyps are necessary to avoid overlooking other diagnoses in addition to polyps.

Incidental Hepatic Tissue Obtained via Cholecystectomy

(Poster No. 3)

Vonny Tunru-Dinh, MD1 (VTunru-Dinh@forumhealth.org); Bryan Myint, HS2; Mark L. Wu, MD.2 1Department of Pathology, Western Reserve Care System, Youngstown, Ohio; 2Department of Pathology and Laboratory Medicine, University of California Irvine School of Medicine, Orange.

Context: Hepatic tissue that is obtained via cholecystectomy has yet to be studied. Such incidental hepatic tissue might contain clinically useful diagnostic information. Furthermore, evaluating this hepatic tissue might result in billable procedures that increase revenues.

Design: We retrospectively reviewed 50 specimens, from consecutive cholecystectomies, which were received without fixative and were resected and prosected by pathologists who had no knowledge of our study. One section from the fossa for gallbladder was submitted from each specimen. We let $X and $2X represent hypothetical revenue generated by specimens without and with examination of hepatic tissue, respectively.

Results: Twelve specimens (24%) contained hepatic tissue. The hepatic tissue per specimen had a total length of 0.2 to 44.5 mm and contained 11 or fewer portal tracts. Each piece of hepatic tissue was 0.2 to 1.7 mm wide. Five specimens contained pieces of hepatic tissue that were as large as those obtained by core biopsies (Figure 12, bottom), and 2 specimens contained hepatic tissue that met criteria for adequacy regarding core biopsies. Surprisingly, most hepatic tissue was adequately preserved and only mildly autolyzed or cauterized. Diagnostic findings included hepatocanalicular cholestasis, steatosis, von Meyenburg complex, and absence of fibrosis confirmed by trichrome stain. Examining hepatic tissue increased total hypothetical revenue from $50X to $62X (24%).

Conclusions: Cholecystectomy commonly removes pieces of hepatic tissue, which can be as large as specimens obtained by core biopsies, can be well preserved, and can contain clinically useful diagnostic information. Examining such hepatic tissue also significantly increases revenues.

Giant Ganglia in Colonic Inertia

(Poster No. 4)

Kaveh Naemi, DO1 (knaemi@uci.edu); Kashyap Trivedi, MD2; Michael J. Stamos, MD3; Mark L. Wu, MD.1 Departments of 1Pathology and Laboratory Medicine, 2Internal Medicine, and 3Surgery, University of California Irvine School of Medicine, Orange.

Context: Colonic inertia is a rare type of severe idiopathic chronic constipation requiring colectomy and is characterized by abnormal colonic transit. The histologic criteria of colonic inertia have yet to be fully characterized. The role of giant submucosal ganglia in the setting of colonic inertia has yet to be studied.

Design: We retrospectively reviewed hematoxylin-eosin-stained sections of specimens from all cases of colonic inertia accessioned at our institution between 1992 and 2008. Giant ganglia were defined as ganglia with more than 8 perikarya. We introduced the term massive ganglia to refer to ganglia with 20 or more perikarya. For each specimen, the numbers of giant and massive ganglia were counted.

Results: Material from 6 patients was examined. The number of giant plus massive ganglia in each patient ranged from 12 to 39. Giant ganglia and massive ganglia occupied both Meissner plexus and Henle/Schabadasch plexus. Surprisingly, 1 giant ganglion was mitotically active. All but 1 of the patients had 1 or more massive ganglion (Figure 13). However, for this patient, only 3 histologic sections were available for review, and yet this limited sample revealed a giant ganglion with 17 perikarya.

Conclusions: We performed the first study of submucosal giant ganglia in the setting of colonic inertia and showed that frequent giant ganglia, massive ganglia, and mitotically active ganglia may be seen. Adequate sampling is necessary to detect massive ganglia and mitotically active ganglia. Further studies are necessary to determine whether these findings can be considered as diagnostic features of colonic inertia.

Effect of Colchicine Therapy on the Gastrointestinal Tract: A Mimicker of Dysplasia and Inflammatory Bowel Disease

(Poster No. 5)

Alma R. Reyes,MD (alma.reyes@beaumont.edu); Harsha S. Desai, MD; Maryam A. Farinola, MD. Department of Anatomic Pathology, William Beaumont Hospital, Royal Oak, Mich.

Context: Colchicine is an antimitotic alkaloid most commonly used to treat gout. To our knowledge, there is only one other study in the literature that has assessed the morphologic findings of colchicine therapy throughout the entire gastrointestinal tract.

Design: Our study consists of 6 patients ranging from 10 to 88 years who were treated with colchicine primarily for gouty arthritis. Multiple biopsies from various gastrointestinal sites were reviewed for each patient. Morphologic features, such as metaphase arrest, ringed mitosis, epithelial pseudostratification, and apoptosis, were assessed on a 3-point scale.

Results: Metaphase arrest was seen in 100% of the biopsies. Ringed mitosis was observed in 100% of colonic and gastroesophageal junction biopsies, 86% of small bowel biopsies, 60% of antrum biopsies, and 0% of stomach-body biopsies. Epithelial pseudostratification was identified in 71% of small bowel biopsies, 67% of colonic biopsies, 60% of antrum biopsies, and 0% of stomach-body biopsies. Apoptosis was identified in 100% of gastroesophageal junction biopsies, 67% of colonic biopsies, 60% of antrum biopsies, 14% of small bowel biopsies, and 0% of stomach-body biopsies.

Conclusions: Our results show that metaphase arrest, ringed mitoses, pseudostratification, and apoptosis are the most distinct morphologic changes resulting from colchicine therapy and are most prominent in the gastroesophageal junction, small intestine, colon, and antrum, with relative sparing of the body of the stomach. It is important that the histologic features of colchicine therapy, although not specific, be known because they can mimic inflammatory bowel disease and dysplasia.

Primary Invasive Micropapillary Carcinoma of the Colon: A Case Report With Clinicopathologic and Immunohistochemical Review

(Poster No. 6)

Harsha S. Desai, MD (harsha.desai@beaumont.edu); Alma R. Reyes, MD; Tomi J. Kuntzman, DO. Department of Anatomic Pathology,William Beaumont Hospital, Royal Oak, Mich.

Invasive micropapillary carcinoma has been reported in various anatomic sites including salivary glands, breast, lung, pancreaticobiliary, renal pelvis, ureter, urinary bladder, and ovary. Invasivemicropapillary carcinoma of the colon is very rare and only a few cases have been reported in the literature. In this report, we describe a case of primary invasive micropapillary carcinoma of the right colon in an 84-year-old man presenting with bloody stools for the duration of 2 months. Macroscopic examination revealed an indurated, centrally ulcerated mass with rolled heaped-up borders in the ascending colon. Microscopic examination revealed tufts of tumor cells lying within well-demarcated clear spaces resembling lymphovascular channels. There was a combination of micropapillary carcinoma component (80%) and conventional colonic adenocarcinoma component (20%) in this neoplasm. Immunohistochemical staining of the micropapillary component showed positivity for cytokeratin (CK) 20 and negativity for CK7, CK17, p63, and thyroid transcription factor 1. In addition, epithelial membrane antigen confirmed the reverse polarity of the neoplastic cells with membranous staining toward the stromal pole. The differential diagnosis of micropapillary architecture of a primary colonic tumor consists of conventional colonic adenocarcinoma with extensive lymphatic invasion, an artifactual clefting caused by dehydration, and primary invasive micropapillary carcinoma. It is essential to recognize and differentiate this entity because invasive micropapillary carcinoma of the colon is associated with frequent lymph node metastasis and may represent poor prognosis with adverse clinical outcome.

Papillary Mesothelial Proliferation on the Small Bowel Mesentery: A Case Report and Review of the Literature

(Poster No. 7)

Blazej Zbytek, MD, PhD1 (bzbytek@utmem.edu); Heather Baldwin, MD1; Alina F. Jukkola, MD.2 1Department of Pathology and Laboratory Medicine, University of Tennessee Health Science Center, Memphis; 2Department of Pathology/Laboratory Medicine Service, VA Medical Center, Memphis, Tenn.

Mesothelial proliferations encompass several benign and malignant entities. This case report describes a rare variant of a mesothelial lesion encountered in our practice. A 55-year-old man presented with nausea and vomiting for 3 days and diarrhea for 3 weeks. His medical history was significant for end-stage renal disease, hypertension, diabetes mellitus, coronary artery disease, and cataracts. Computed tomography of the abdomen revealed multiple loops of distended small bowel associated with bowel wall thickening, fecalization of small bowel, and pneumobilia. Because of a strong suspicion of bowel obstruction, exploratory laparotomy was performed. During the procedure, the small bowel appeared pink and thickened with a white cast and with multiple nodules present on its mesentery. One of the nodules was biopsied. The nodule had a uniform, papillary pattern. The papillae were branching with fibrovascular cores and were covered by uniform mesothelial cells. The diagnosis of papillary mesothelial proliferation was rendered. If solitary,mesothelial proliferations with this morphology are considered benign. However, if they are multiple, as is suspected in this case, the term well-differentiated papillary mesothelioma is preferred due to the low malignant potential. We will discuss the pathologic findings of well-differentiated papillary mesothelioma in the abdominal cavity and review the data in our database regarding abdominal mesothelial proliferations. Finally, we will review the literature on the subject.

Smoothelin Is Superior to Smooth Muscle Actin in the Investigation of Pediatric Intestinal Motility Disorders

(Poster No. 8)

Vinay Prasad, MD (vinay.prasad@nationwidechildrens.org); Ronald Houston, MS. Department of Pathology, Nationwide Children's Hospital, Columbus, Ohio.

Context: Intestinal dysmotility commonly affects children. Full-thickness biopsies are obtained more frequently than before. We found a panel of antibodies to be extremely useful in studying each component of the motility system. Smoothelin is a vital addition to S100, PGP 9.5, and CD117. Smoothelin is a constituent of smooth muscle cell cytoskeleton and a novel marker.

Design: Four patients with symptoms of intestinal dysmotility, including 2 girls and 2 boys aged 1, 2, 8, and 11, were studied. The patients' symptoms included chronic constipation, nonfunctioning gastroduodenostomy, dysfunctional appendicostomy, and ileostomy prolapse. Additionally, 1 "normal" age- and gender-matched control for each patientwas studied from archival autopsy material using a panel of stains including S100, PGP 9.5, CD117, smoothelin, smooth muscle actin, and trichrome.

Results: In all cases, smoothelin showed very strong and crisp cytoplasmic staining within the smooth muscle cells of the muscularis propria and muscularis mucosae, indicating no abnormality in the smooth muscle component. Myofibroblasts and myoepithelial cells did not stain with smoothelin, but smooth muscle actin highlighted such cells. In our series, abnormalities in ganglion cells and interstitial cells of Cajal were noted in 2 cases by S100, PGP 9.5, and CD117 staining patterns. One was a case of Hirschsprung disease; the other was a case of intestinal dysganglionosis. One case had paucity of interstitial cells of Cajal, while the fourth case had no demonstrable abnormality.

Conclusions: Smoothelin is vital in evaluating smooth muscle wall integrity in the bowel in pediatric dysmotility. Abnormal entericmuscle can be identified with smoothelin.

The Role of Activation of Akt-mTOR-p70S6K Pathway in Liver Neoplasm

(Poster No. 9)

Wei Li, MD1 (Wei.Li@uth.tmc.edu); Zhaoping Zhang, MD.2 1Department of Pathology and Laboratory Medicine, The University of TexasMedical School at Houston; 2Department ofMolecular Genetics, TheUniversity of Texas M. D. Anderson Cancer Center, Houston.

Context: The Akt-mTOR-p70S6K signal pathway has been recognized for its roles in regulating neoangiogenesis. The role of activation of the pathway in hepatocellular carcinoma (HCC) progression has been little analyzed. This study aims to evaluate expression of the phosphorylated forms of the 3 key constituent proteins (Akt, mTOR, and p70 S6K) of AktmTOR-p70S6K signal pathway in HCC tissue and non-HCC tissue.

Design: Formalin-fixed, paraffin-embedded tissue sections of 51 HCCs, 9 hepatocellular adenomas, 48 cirrhotic nodules, and 17 normal liver tissues were immunostained for p-Akt, p-mTOR, and p-p70 S6K. Expression of these proteins was graded on a scale from 0 to 3 (from negative to strong) based on number of immunoreactive endothelial cells and the degree of staining intensity.

Results: The number of p-Akt- and p-p70 S6K-positive sinusoidal endothelial cells and the intensity of immunostaining were significantly higher in HCC compared with hepatocellular adenoma, cirrhotic nodules, and normal liver tissues (P = .005). Expression of p-mTOR in sinusoidal endothelial cells appeared to be increased in HCC tissue compared with non-HCC tissue. There was significant correlation between high p-Akt and p-p70 S6K expression and venous invasion by HCC. No significant difference for p-Akt and p-p70 S6K expression was observed between hepatocellular adenoma and cirrhotic nodules and between hepatocellular adenoma and normal liver tissues.

Conclusions: Activation of Akt-mTOR-p70S6K pathway plays a significant role in HCC progression by promoting neoangiogenesis. Molecular strategies aimed at inhibiting this signal pathway might be of therapeutic use for the treatment of HCC.

Postorthotopic Liver Transplant Biopsies From Patients With Type 2 Diabetes Mellitus and Recurrent Hepatitis C Virus Infection Are Associated With Increased 4-Hydroxy-2-Nonenol Staining and Anisokaryosis

(Poster No. 10)

Redouane Boumendjel, MD1 (rboumendjel@sbcglobal.net); Nina Singh, MD2; Alberto Locante, MD1; Eric Kallwitz, MD2; Gregorio Chejfec, MD1; Tibor Valyi-Nagy, MD1; Grace Guzman, MD1; Roshan Patel, MD.1 Departments of 1Pathology and 2Medicine, University of Illinois at Chicago.

Context: The significance of anisokaryosis in liver tissue is not well understood. 4-Hydroxy-2-nonenol (4-HNE) monoclonal antibody (Genox, Baltimore, Md) is an immunohistochemical marker for oxidative protein damage that is mediated by the lipid peroxidation byproduct, 4-HNE.We evaluated whether lipid peroxidation was associated with anisokaryosis in benign hepatocytes from hepatitis C virus-reinfected orthotopic liver transplant (OLT) recipients with and without type 2 diabetes mellitus (T2DM).

Design: Protocol liver biopsies of 21 OLT recipients with recurrent hepatitis C virus with and without T2DM were studied. Cases with rejection, dysplasia, and malignancy were excluded. Paraffin-embedded tissue sections (n = 37, plus normal liver control) stained with 4-HNE were classified as low (<20% of cells) and high positive. Nuclear size wasmeasured in 100 hepatocytes in 10 high-power fields (×400) using The ScanScope System (Aperio Technologies, Inc, Vista, Calif). A nuclear size of less than 5.00 µm was classified as low and 5.00 µm and greater as high (range, 3.00-10.50 µm). Data analysis was performed using nonparametric statistics and χ^sup 2^ testing.

Results: Twenty-one subjects (mean age, 51 years), with 20 of 37 biopsies associated with T2DM, had a median nuclear range with T2DM of 5.28 µm versus 4.00 µm without T2DM (P = .03), as well as 6.20 µm with a high percentage versus 4.10 µm with a low percentage of 4-HNE staining (P = .03). The median nuclear range was 2.00 µm in normal liver control tissue.

Conclusions: Increased range of anisokaryosis by digital measurement of nuclear size is associated with the presence of T2DM and heightened immunohistochemical detection of 4-HNE-mediated oxidative damage in hepatitis C virus-reinfected OLT recipients.

An Unusual Site for Colorectal Metastasis

(Poster No. 11)

Elham Khanifar, BM, BCh1 (khanifae@uci.edu); Wendy R. Brewster, MD, PhD2; Imad Shbeeb, MD3; Robin Simpkins, HT(ASCP)4; Joanne Rutgers, MD.4 Departments of 1Pathology and Laboratory Medicine and 2Gynecologic Oncology, University of California, Irvine, Orange; Departments of 3Colorectal Surgery and 4Pathology, Todd Cancer Institute, Long Beach Memorial Medical Center, Long Beach, Calif.

Context: Most vaginal adenocarcinomas are metastatic, and colorectal carcinoma (CRC) can involve the vagina by direct extension. A sentinel case of CRC metastatic to the anterior vagina prompted us to review our files.

Design: A SNOMED search identified all cases of colorectal and vaginal adenocarcinomas from 2000 to 2005. All available slides and medical charts were reviewed.

Results: During this period, our institution treated 662 CRC cases, including 360 females, and 34 cases of vaginal adenocarcinoma. Of the latter, 3 (9%) were primary and 31 (91%) were metastatic (Table). Five cases of CRC involved the vagina (incidence, 1.4% in females). Three had vaginal involvement at presentation, and one had vaginal recurrence at the anastomotic site 30 months after resection. The sentinel patient had surgical resection of rectal adenocarcinoma 13 years after transvaginal hysterectomy for benign disease. The tumor was staged T3 N0 (0/12 nodes) M0, with lymphovascular space involvement. Twenty months later, she developed a 1-cm anterior-superior vaginal metastasis and underwent surgical resection and radiation therapy. A solitary lung metastasis and second vaginal metastasis were resected at 40 and 49 months, respectively. The metastatic lesions were histologically and immunohistochemically identical to the original rectal adenocarcinoma, with cytokeratin (CK) 7-negative and CK20- and CDX2-positive reactivity.

Conclusions: Our study confirmed that CRC is the most common nongynecologic primary metastatic to the vagina. Our sentinel case is unique in the anterior location of the vaginal metastasis. We hypothesize that this may be due to the patient's altered lymphovascular drainage secondary to remote hysterectomy.

Obstructive Biliary Disease Mimicking Caroli Disease

(Poster No. 12)

Elham Khanifar, BM, BCh1 (khanifae@uci.edu); Bita Behjatnia, MD2; Joanne Rutgers, MD.3 1Department of Pathology and Laboratory Medicine, University of California at Irvine, Orange; 2Department of Pathology and Laboratory Medicine, University of California, Los Angeles; 3Department of Pathology, Long Beach Memorial Medical Center, Long Beach, Calif.

We present a case of common bile duct injury causing an acquired Caroli-like dilatation of the intrahepatic ducts. A 50-year-old white woman underwent cholecystectomy for symptomatic cholelithiasis, but subsequently developed biliary leakage requiring a cholangiojejunostomy. The patient recovered, but at 11 months complained of increasing jaundice. Abdominal ultrasound and magnetic resonance cholangiopancreatography showed dilated bile ducts in the left lobe of the liver and a left liver lobectomy was performed. Grossly the lobe had green discoloration and showed fibrosis surrounding segmental bile ducts dilated to 2 to 3 mm. Microscopically, the dilated bile ducts showed focal stones, columnar change of the biliary epithelium with acute inflammation, and surrounding fibrosis. The liver parenchyma showed prominent cholestasis without fibrosis. The patient had relief of symptoms, but returned 1 month later with worsening jaundice and fevers. Imaging showed right-sided biliary dilatations ranging from 0.4 to 2 cm. Percutaneous cholangiography confirmed continuity of these cystic spaces with the biliary tree; however, the cholangiojejunostomy anastomotic site was stenotic necessitating a balloon cholangioplasty. Incidental renal cysts were also noted. This unusual case shows sequential lobar presentation of dilated segmental bile ducts and ascending cholangitis, mimicking Caroli disease. Caroli disease is a genetically inherited condition that can present at any age and involve one or both liver lobes. In contrast to the current case, saccular dilations are more prominent in Caroli. Biliary obstruction and Caroli disease should both be considered in the differential diagnosis of a patient with cystically dilated bile ducts and ascending cholangitis (Figure 14).

The Critical Role of Ultrastructural Morphology in Diagnosing an Abdominal Neoplasm

(Poster No. 13)

Keith D. Bohman, MD (kbohman14@aol.com); William T. Gunning, PhD. Department of Pathology, University of Toledo, Toledo, Ohio.

In some instances, an abdominal neoplasm in females may pose difficult diagnostic challenges. Clinical history and presentation, along with diagnostic assays, including radiologic, light microscopic, and immunocytochemical indicators, are usually sufficient for correctly identifying neoplastic etiologies. We present a rare acinar/acinic cell carcinoma of the pancreas, which required ultrastructural evaluation to render the diagnosis. A 77-year-old woman presented with generalized abdominal bloating and pain of 6 weeks' duration. She had a history of a total abdominal hysterectomy with a bilateral salpingo-oophorectomy 30 years prior due to endometriosis. She was found to have a large omental "cake" and ascites by computed tomography, and her CA 125 level was elevated at 470 U/mL. An exploratory laparotomy revealed extensive metastases; a biopsy was obtained, and the procedure halted. A diagnosis of primary peritoneal carcinoma was initially considered by light microscopy. Subsequently, results of electron microscopy demonstrated the neoplastic cells had abundant rough endoplasmic reticulum and electron-dense granules consistent with the morphology of zymogen granules (Figure 15). A number of granules were also observed with a fibrillary substructure. The ultrastructural morphology was consistent with the phenotype of an acinar/acinic cell carcinoma of the pancreas and not a primary peritoneal carcinoma. The elevated serum CA 125 suggested a primary peritoneal carcinoma given this patient's history. However, when used as a serum marker for the screening of gynecologic malignancies, elevated CA 125 may be misleading; for example, inflammatory disorders of the peritoneum may produce elevated levels as well. Ultrastructural evaluation provided essential evidence to diagnose this neoplasm as pancreatic acinar/acinic cell carcinoma.

Negative Estrogen and Progesterone Receptors, Immunohistochemistry in Hepatoblastoma, and Positive Estrogen Receptor in Adjacent Normal Hepatocytes

(Poster No. 14)

Kenneth C. Whithaus, MD (kwhithaus@usouthal.edu); Zhaung Zuo, MD, PhD; Elizabeth A. Manci, MD. Department of Pathology, University of South Alabama, Mobile.

Context: Hepatoblastoma is the most common childhood malignancy of the liver. Although the presence of estrogen and progesterone receptors in hepatocellular carcinoma, which occurs predominately in adults, has been studied for more than 2 decades, no multicase studies have evaluated hormone receptors in hepatoblastoma. There is a well-documented correlation between exogenous estrogens and the pathogenesis of hepatic neoplasms. Because hepatoblastomas are known to arise in utero, and therefore may be under the influence of maternal hormones, they have the potential to express sex hormone receptors. The aim of this study is to investigate the nature of hormone receptors in hepatoblastoma.

Design: Four cases of hepatoblastoma and 4 nonneoplastic pediatric liver biopsies were studied. The original slides were reviewed for each case. Immunohistochemistry for estrogen and progesterone receptors was performed on all 8 cases.

Results: One of the 4 hepatoblastoma cases demonstrated strong focal positive staining for estrogen receptor in hepatocytes immediately adjacent to the tumor, while the remaining cases were estrogen receptor negative. All 4 cases of hepatoblastoma were progesterone receptor negative. The 4 pediatric nonneoplastic liver control cases were negative for both estrogen and progesterone receptors.

Conclusions: Although hepatoblastoma cells failed to express estrogen or progesterone receptors, the adjacent nonneoplastic hepatocytes in 1 showed strong positive staining for estrogen receptors. This finding suggests a reactive effect in the normal hepatocytes secondary to the hepatoblastoma. Because this finding has not been previously reported, further study is needed to determine its significance, possibly in the subclassification or prognosis of hepatoblastoma.

Sporadic Fundic Gland Polyposis in a Bariatric Patient

(Poster No. 15)

James F. Shikle, MD1 (jfshikle@yahoo.com); Christina D. Hahn, MD.2 Departments of 1Pathology and 2Surgery, Eisenhower Army Medical Center, Fort Gordon, Ga.

Fundic gland polyps were incidentally discovered during preoperative upper endoscopy in a 50-year-old woman desiring bariatric surgery. She had a history of severe gastroesophageal reflux symptoms and had been taking proton pump inhibitors for more than 10 years. Colonoscopy revealed no colonic or rectal polyps. She underwent an uncomplicated resectional Roux-en-Y gastric bypass procedure. Pathologic examination of the gastric remnant revealed numerous polyps carpeting the gastric mucosa and measuring from 0.5 to 2.0 cm in greatest dimension.Microscopic analysis of the polyps demonstrated the classic features of fundic gland polyps with dilated, cystic gastric glands lined by parietal, chief, and mucus neck cells in a normal lamina propria. No dysplasia was present in the polyps, and the background gastric mucosa was normal. Fundic gland polyposis is a rare condition that can occur in the setting of familial adenomatous polyposis or in patients on acid suppression therapy with proton pump inhibitors. The polyps almost always measure less than 1.0 cm. This case of fundic gland polyposis with polyps measuring up to 2.0 cm in the setting of morbid obesity and a surgical specimen highlights the usefulness of preoperative endoscopy and submission of all gastric bypass specimens for microscopic evaluation (Figure 16).

Summit Lesions Are a Marker for Clostridium difficile Colitis

(Poster No. 16)

Leana A. Guerin, MD (leana-guerin@uiowa.edu); Frank A. Mitros,MD. Department of Pathology, The University of Iowa Hospitals and Clinics, Iowa City.

Context: Pseudomembranes seen in Clostridium difficile colitis are a late and obvious finding in the disease process. Earlier changes, termed summit lesions, were first described by Price and Davies in 1977. Summit lesions are raised clusters of damaged epithelial cells in the intercryptal surface epithelium. The purpose of this study was to evaluate the summit lesion in its ability to predict C difficile colitis.

Design: The study population was found by searching our institution's surgical pathology database for the terms summit lesion, toxin, or pseudomembrane. Slides were reviewed independently by 2 pathologists and scored from 0 to 3+ for the presence and strength of summit lesions. Clinical data, including C difficile assay results, were collected for each case.

Results: Fifty-four cases were identified; 20 of these were excluded because of either an absent C difficile toxin assay or recent C difficile treatment. The reviewers' scores agreed on 36 (67%) of 54 cases, with good agreement when distinguishing 3+ and less than 3+ summit lesions (κ = 0.674). A case was considered positive for summit lesions if at least one of the reviewers scored the case 3+. A 2 × 2 contingency table was constructed and analyzed using Fisher exact test (Table). The 2-tailed P value (.002) was statistically significant.

Conclusions: The summit lesion has a histologic appearance that can be recognized with good interobserver agreement. The presence of 3+ summit lesions appears to be useful in recognizing and suggesting C difficile colitis in cases that might otherwise have been considered nonspecific colitis.

The Elusive Pathologic Lesion of Angiodysplasia of the Colon Revisited on the Strength of 4 Cases With a Proposal for the Mechanism of Bleeding

(Poster No. 17)

William L. Thelmo, MD1 (drthelmo@bqhcny.org); Cesar D. Del Rosario, MD1; Yaspal Arya, MD2; Pradeep Chandra, MD.2 Departments of 1Pathology and 2Medicine, Wyckoff Heights Medical Center, Brooklyn, NY.

Context: The pathologic lesion of angiodysplasia of colon has been described. However, the precise mechanism of the cause of bleeding has not yet been elucidated. Demonstration of the vascular lesion and defining the precise site of rupture is a "histologic tour de force."

Design: We studied 4 patients who presented with massive lower gastrointestinal bleeding and underwent partial colectomies. We used 10 cases (age matched) from colonic cancer resections as control.We opened the colon immediately (within 2 hours) and submerged the entire colon in 10% buffered formalin mixed with 95% alcohol (50:50 ratio). Following overnight fixation, histologic sections were made based on gross inspection and transillumination.

Results: All 4 cases showed dilated lumen and diverticulosis. No source of bleeding was identified, despite microscopic study of all diverticuli. There were no ulcers, hemangiomas, or congeries of small or large blood vessels seen. The only significant gross finding was focal areas of hyperemia in the mucosa. Histologic sections (stained with hematoxylineosin and Masson trichrome) from these areas showed dilated and congested pericryptal and subepithelial blood vessels with diapedesis of red blood cells through the subepithelial basement membrane.

Conclusions: Based on the findings, we propose that the increased intraluminal pressure (corroborated by dilatation of the colon and extensive diverticulosis) is a major factor in angiodysplasia. It leads to increased venous stagnation, leads to retrograde increased pressure in the pericryptal capillary vessels including subepithelial capillaries, and facilitates diapedesis of red blood cells into the lumen of the colon. Thiswould lead to clinical manifestation of lower gastrointestinal bleeding.

Characterization of Messenger RNA Expression Spectra of Homeobox Genes in the Normal Gastrointestinal Tract and Colon Cancer Cell Lines: Potential Utility in Colon Cancer Diagnosis

(Poster No. 18)

Zhe Piao, MD, PhD1 (zpiao@ucsd.edu); Owen Chan, MD, PhD1; Lawrence A. Hansen, MD1; Henry C. Powell, MD, DSc1;Manuel Perucho, PhD.2 1Department of Pathology, University of California at San Diego Medical Center, San Diego; 2Tumor Development Program, The Burnham Institute for Medical Research, La Jolla, Calif.

Context: Homeobox genes are transcription factors and are expressed organ specifically; therefore, antibodies against them would be useful in discerning the origin of a tumor. However, the expression spectra of homeobox genes in gastrointestinal tract and their utility for the pathologic diagnosis of cancers have not been delineated.

Design: To find a sensitive and colon-specific tumor marker, we observed the messenger RNA expression spectra of 16 homeobox genes from the normal gastrointestinal tract and 13 colon cancer cell lines. Reverse transcription-polymerase chain reaction was performed with the specific primer set for each homeobox gene.

Results: Organ-specific expression of the homeobox genes was as follows: HoxD13, descending colon and rectum; HoxC5, stomach and small intestine; HoxC6A and HoxC6B, jejunum and ileum; HoxC9 and HoxC10, small and large intestine; and HoxC1, small intestine. Homeobox gene expression in the 13 colon cancer cell lines was enumerated as follows: CDX1 (8/13), HoxA4 (9/13), HoxA5 (10/13), HoxD1 (12/13), HoxD3 (10/13), HoxD8 (6/7), HoxD9 (9/13), HoxD12 (8/13), HoxD13 (9/13), HoxC5 (12/13), HoxC6A (12/13), HoxC6B (12/13), HoxC9 (12/13), HoxC10 (11/13), HoxC11 (11/13), and HoxC13 (13/13). HoxC5, HoxC6A, HoxC6B, and HoxC11, which were not expressed in the normal colon tissue, were aberrantly expressed in the colon cancer cell lines.

Conclusions: There is an organ-specific expression of homeobox genes in certain regions of the normal gastrointestinal tract. The aberrant expression of homeobox genes may be helpful in establishing the differential diagnosis of colon cancer from other adenocarcinomas; and the cancerassociated expression pattern of some homeobox genes may be helpful in the early diagnosis of colon cancer.

Gastric Metaplasia: A Frequently Overlooked Feature of Duodenal Carcinoid Tumors

(Poster No. 19)

Ji-Weon Park, MD (jiwpark@notes.cc.sunysb.edu); Jingxuan Liu, MD; Sui Zee, MD. Department of Pathology, Stony Brook University Medical Center, Stony Brook, NY.

Context: Carcinoid tumors are relatively uncommon neuroendocrine tumors. Those located in the duodenum account for only 2.6% of carcinoid tumors in the United States. Although the histologic and immunohistochemical aspects of duodenal carcinoids have been well studied, the associated epithelial changes have not been described in previous English literature. In this study, we examine the incidence of gastric metaplasia in the presence of duodenal carcinoid tumors.

Design: The authors reviewed all cases diagnosed as duodenal carcinoid from the pathology department database of Stony Brook University Hospital (1980-2007). A total of 7 cases from 5 patients were identified. Histologic examination was performed on all cases, with particular attention to the epithelium overlying and adjacent to the tumor. Each specimen was stained for presence of intestinal-type epithelium with Alcian blue (pH 2.5).

Results: All specimens had evidence of carcinoid tumor (confirmed by histologic examination and/or immunohistochemical stains). All carcinoids showed evidence of gastric metaplasia as characterized by gastricfoveolar-type columnar to cuboidal epithelial cells in the overlying/adjacent mucosa (negative for Alcian blue). The rest of the epithelium was composed of goblet cells and absorptive intestinal-type villous epithelium (positive for Alcian blue).

Conclusions: To our knowledge, this is the first study describing gastric metaplasia associated with carcinoid tumors. Identifying gastric metaplasia in association with duodenal carcinoid tumors may help to elucidate possible mechanism and pathogenesis of these tumors. It may also serve a role as a marker in identification and early detection of duodenal carcinoid tumors. Additional studies may further determine whether there are possible prognostic implications.

CD56 Is Useful in Differentiating Foregut Gastrointestinal Neuroendocrine Tumors From Midgut or Hindgut and World Health Organization Grade 1 From Grade 2 or Grade 3 Tumors

(Poster No. 20)

Xueping Fang, MD1 (xfang3@buffalo.edu); Weiguo Liu, MD1; Renuka Iyer, MD2; Dongfeng Tan, MD3; Midhat Arnouk, MD2; Badari Ambuga, MD2; Sadir Alrawi, MD2; Thaer Koury, MD.4 1Department of Pathology, The State University of New York at Buffalo; Departments of 2Medicine and 4Pathology, Roswell Park Cancer Institute, Buffalo, NY; 3Department of Pathology, M. D. Anderson Cancer Center, Houston, Tex.

Context: Gastrointestinal neuroendocrine tumors (GINETs) can arise in foregut, midgut, and hindgut. These tumors differ from each other based primarily on their anatomic sites. We examine the expression of CD56 in GINET and assess its role in differentiating the different sites of origin for GINET.

Design: Cases of primary GINET were retrieved from the files of Roswell Park Cancer Institute (1995-2005). CD56 was immunohistochemically performed on all cases. A semiquantitative scoring system using percentage of stained cells multiplied by the staining intensity was used. Final scores ranged from 0 to 300, and a score of 30 or greater was considered positive. Fisher exact test was used for statistical analysis.

Results: Among 53 GINETs, 17, 23, and 13 were of foregut, midgut, and hindgut origin, respectively. Nine (20%), 31 (68.9%), and 5 (11.1%) of 45 cases were classified as grade 1, 2, and 3 GINET, respectively. CD56 was positive in 16 (94.1%) of 17 foregut, 4 (17.4%) of 23 midgut, and 6 (46.2%) of 13 hindgut tumors (P < .001). CD56 was positive in 8 (88.9%) of 9 World Health Organization (WHO) grade 1, 11 (35.5%) of 31 WHO grade 2, and 2 (40%) of 5 WHO grade 3 GINET (P = .01).

Conclusions: The frequency of CD56 expression differs significantly depending on the tumor location and grade. CD56 is more commonly expressed in WHO grade 1 than in grades 2 or 3 GINET. CD56 may serve as a useful diagnostic parameter to determine the tumor location and to differentiate low-grade from higher-grade GINET.

Incidental Reduction in Size of Liver Hemangioma Following Use of Avastin (Vascular Endothelial Growth Factor Inhibitor) for Treatment of Metastatic Colorectal Carcinoma

(Poster No. 21)

Dipti Mahajan, MD1 (mahajad@ccf.org); Charles Miller, MD2; Kenzo Hirose, MD2; Lisa Yerian, MD.1 Departments of 1Pathology and Laboratory Medicine and 2Surgery, Cleveland Clinic Foundation, Cleveland, Ohio.

Hepatic cavernous hemangioma is the second most common tumor seen in the liver after metastases. Vascular endothelial growth factor (VEGF) is recognized as an essential regulator of blood vessel growth. It is postulated that high VEGF expression leads to increased angiogenic activity in cavernous hemangioma endothelial cells. The use of specific antibodies directed against VEGF abolishes this vascular endothelial growth-promoting activity in vitro. Bevacizumab (Avastin) is a recombinant humanized monoclonal antibody directed against VEGF that is used for the treatment of metastatic colorectal cancer in combination with 5-fluorouracil-based regimens. We report on a patient with invasive colorectal adenocarcinoma and suspected liver metastasis on radiologic examination. Liver lesions in this patient showed a significant decrease in size after treatment with bevacizumab (Avastin) following colectomy. Histology of the liver lesions revealed hemangioma (Figure 17); no metastatic adenocarcinoma was identified. Staining for VEGF (Chemicon International, Inc, Temecula, Calif) (Figure 17, inset) and anti-VEGFr2 (Cell Signaling, Inc, Danvers, Mass) (Figure 17, inset) antibody revealed strong staining in the hemangioma endothelial cells. To date, despite other modalities, surgical resection provides the only consistently effective method for hepatic hemangioma. This is the first case report describing the successful incidental use of an anti-VEGF drug in the treatment of a vascular tumor such as hemangioma. VEGF-signaling blockade poses a potential new treatment modality for vascular neoplasms and holds promise in the use of Avastin for treatment of hemangiomas in the liver and other sites.

Extrapulmonary Sarcoidosis of the Liver: A Case Report and Review of Literature

(Poster No. 22)

Ashish Bains, MD1 (ashish-bains@ouhsc.edu); Jennifer Holter, MD2; Kar-Ming Fung, MD.1 Departments of 1Pathology and 2Hematology/Oncology, Oklahoma University Health Sciences Center, Oklahoma City.

Sarcoidosis is a multisystemic disease of uncertain etiology, most commonly affecting the lungs. However, unusual cases may present with extrapulmonary manifestations.We present a case with hepatosplenomegaly as a primary feature. A 56-year-old woman presented with constitutional symptoms of vague abdominal pain, fullness, fatigue, and weight loss. A computed tomography scan showed normal pulmonary and mediastinal anatomy with a moderately enlarged liver and spleen. Her laboratory data, including routine chemistries and complete blood count,were within normal limits, except a borderline low platelet count. Results of liver function tests were normal. Antimitochondrial antibody, antinuclear antibody, antineutrophil cytoplasmic antibodies, and anti-smooth muscle antibody were all negative. A liver biopsy was performed. The biopsy specimen revealed a nonnecrotizing epithelioid granulomatous inflammation. There were few dispersed giant cells and focal bridging fibrosis. The interlobular bile ducts were decreased. Immunohistochemical stains showed reticulin fibers extending into the granuloma. Acid-fast stain and periodic acid-Schiff stain were negative for microorganisms (Figure 18). Considering the clinical and histologic findings, the possibility of sarcoidosis was seriously entertained. Follow-up blood work disclosed an elevated angiotensin converting enzyme level. Exclusive liver involvement is documented in only about 13% of systemic sarcoidosis patients. Most patients with hepatic sarcoidosis are asymptomatic and usually with normal liver function tests and are often discovered during the workup for abnormalities on computed tomography scan. A broad spectrum of conditions can cause hepatic granulomas, and the alternative diagnosis must be excluded based on clinical history, prevalence of infectious diseases, and other relevant laboratory testing.

Ground Glass Hepatocytes Induced by Phenytoin: Report of First Case

(Poster No. 23)

Tomomi L. Billings, MD1 (tbilling@uci.edu); Eugene Yoon, MD2; John C. Hoefs, MD2; Mark Li-Cheng Wu, MD.1 Departments of 1Pathology and 2Medicine, University of California at Irvine, Orange.

Ground glass hepatocytes are known to represent accumulated hepatitis B surface antigen. Many disorders produce cytoplasmic changes that closely resemble ground glass hepatocytes. Ground glass hepatocytes in the setting of hepatotoxicity due to phenytoin have yet to be convincingly established. We present the first case to link ground glass hepatocytes to phenytoin. The patient was a 59-year-old Asian man with newly diagnosed classical Hodgkin lymphoma, mixed cellularity subtype, who presented with pruritic rash, fever, and chills. He was taking phenytoin to treat seizures caused by an intracranial mass suspicious for lymphoma. Serology showed markedly elevated hepatic transaminases and negative tests for hepatitis B and C viruses. Percutaneous hepatic core biopsy was performed prior to chemotherapy. Microscopy showed changes characteristic of hepatotoxicity due to phenytoin, including sinusoidal beading of lymphocytes, granulomas, apoptotic hepatocytes, and mitotically active hepatocytes. Frequent hepatocytes had prominent homogeneous amphophilic inclusions (Figure 19), which retracted from the cytoplasm and often indented nuclei. Many inclusions were morphologically identical to ground glass hepatocytes associated with hepatitis B virus. Cytochemistry, immunohistochemistry, and electron microscopy showed the inclusions to be congophobic, to be negative for periodic acid-Schiff, colloidal iron, or hepatitis B surface antigen, and to lack organelles, fibrils, or viral particles. These findings excluded globular amyloid, Lafora bodies, and glycogenstorage disease type IV from diagnostic consideration. Our final interpretation was ground glass hepatocytes in setting of hepatotoxicity due to phenytoin. Awareness of this phenomenon is necessary to avoid diagnostic confusion between ground glass hepatocytes due to hepatitis B surface antigen and other entities.

Clinicopathologic Features Affecting Recurrence of Hepatocellular Carcinoma After Liver Transplant: An Analysis of 34 Patients

(Poster No. 24)

Fadi Habib, MD (fhabib1@hfhs.org); Mona Bansal, MD; Veena Shah, MD. Department of Clinical and Anatomic Pathology, Henry Ford Health System, Detroit, Mich.

Context: Hepatocellular carcinoma (HCC) has a dismal prognosis, especially in patients with extensive tumors. Features, including both clinical and pathologic, that predict recurrence of HCC have not been well described. We analyzed and compared clinical and pathologic features of 34 patients with or without recurrence of HCC to identify those at risk for recurrence.

Design: Thirty-four explant liver cases, including 13 cases with recurrence of HCC, were simultaneously reviewed by a hepatobiliary pathologist and 2 residents. Clinical features, including age at diagnosis, underlying disease, α-fetoprotein levels, and neoadjuvant therapy, were evaluated. Pathologic features including tumor number, edge (pushing or infiltrative), mitotic figures per 10 high-power fields, stroma for desmoplasia (absent, focal, extensive), inflammation around tumor (0 = none, 1 = mild, 2 = moderate, 3 = severe), necrosis (absent, focal, extensive), vascular invasion, and grade were evaluated. Tissue microarrays were prepared. Proliferation marker Ki-67 was performed and was interpreted as percentage of nuclear positivity.

Results: A significantly greater proportion of patients with recurrence had 4 or more tumors (Table). On the other hand, patients with 1 tumor had lower incidence of recurrence (P = .005). Two single tumors measuring 2.1 and 2.5 cm also recurred. Most common cause of underlying disease was hepatitis C. Inflammation, necrosis, mitosis, α-fetoprotein levels, age, and gender did not have any impact on recurrences.

Conclusions: Multiple tumors (>4) are more likely to recur as compared with single tumors. Providing neoadjuvant chemotherapy did not prevent recurrence. Both Ki-67 positivity and mitosis were not statistically significant, but they were higher overall in patients with recurrence, thus indicating a high proliferative index.

CK20 Immunoreactive Carcinoma in the Liver-Not Always a Metastasis

(Poster No. 25)

Daniel A. Smith, DO, PhD1 (dansmith@swmail.sw.org); Thomas J. Sebo, MD, PhD2; Walter J. Linz, MD, MBA.1 1Department of Pathology, Scott and White Memorial Hospital, Temple, Tex; 2Department of Anatomic Pathology, Mayo Clinic, Rochester, Minn.

Cytokeratin (CK) 20 is a low-molecular-weight cytokeratin known to be present in most colorectal adenocarcinomas and Merkel cell carcinomas. It is very unusual for CK20 to be expressed in primary hepatocellular carcinoma (HCC). This report presents an unusual case of a HCC that demonstrates strong CK20 immunoreactivity. It also demonstrates the utility of albumin messenger RNA (using in situ hybridization) to help clarify the nature of a difficult hepatocellular malignancy. A 52-year-old man of Asian decent without prior history of liver disease presented to his physician with right upper quadrant pain. After initial evaluation, he was referred to our institution for second opinion and definitive therapy. Computed tomography scan of the liver identified a large mass and needle biopsy showed a poorly differentiated tumor with a trabecular morphology. Immunostudies showed the tumor to be immunoreactive with pCEA, CK8/18, CK20, albumin messenger RNA (in situ), and CK7 (focally). The tumor was negative for mCEA, -fetoprotein, hepatocyte paraffin 1, S100, CD10, and thyroid transcription factor 1. Serologic studies revealed the presence of HepB surface antigen (chronic carrier state). A diagnosis of high-grade HCC was rendered. To date, further clinical evaluation has not identified another primary tumor site. Primary hepatocellular carcinoma may strongly express CK20. Consequently, a CK20 immunoreactive carcinoma in the liver should not, by default, be considered a metastasis. Albumin messenger RNA (in situ) is a useful adjunct when evaluating a hepatocellular malignancy.

Giant Fibrovascular Polyp of the Esophagus: Recurrence After a 6-Year Interval

(Poster No. 26)

Naomi Montague, MD (NMontague@med.miami.edu); Stephen E. Vernon, MD. Department of Pathology, University of Miami/Jackson Memorial Hospital, Miami, Fla.

A 59-year-old man was admitted for resection of a recurrent polypoid mass arising from the posterior cricoid region of the esophagus. Six years earlier, a 5 × 3 × 1-cm polyp had been excised from the same region with an unremarkable recovery. For this admission, he presented with a tubular mass that he was able to voluntarily partially expel from his mouth. A barium swallow and upper endoscopy showed a soft tissue density in the proximal esophagus. At surgery, a bilobed polyp was resected. Grossly, a 3-cm stalk was connected to 2 lobes (5 × 2 × 2 and 4 × 3 × 2 cm) covered by a freely mobile, smooth mucosal surface. Cut surfaces showed grey-white to yellow masses. Microscopic sections showed an intact squamous epithelium with a compact lamina propria, overlying well-circumscribed but unencapsulated masses of adipose and fibrovascular tissue. Myxoid change, rare chronic inflammatory cell aggregates, and mast cells were also noted. Review of the previously excised esophageal mass showed virtually identical histologic features. Unique to the esophagus, this lesion's origin remains controversial, with ongoing debate as to whether it is neoplastic, hamartomatous, or reactive.Reported cases show a male predominance in older adults, with rare cases of death by asphyxiation. Only 2 other cases of recurrence, after intervals of 8 and 17 years, have been reported. A comparison with other cases from our files did not show any features that may have predicted recurrence.

Spasmolytic Polypeptide-Expressing Metaplasia as an Indicator for Increased Risk of Developing Gastric Adenocarcinoma

(Poster No. 27)

Abstract Withdrawn

Posttransplant Lymphoproliferative Disorders in Multivisceral Transplantation: Approach to Optimize Early Diagnosis

(Poster No. 28)

Carlos E. Parra-Herran, MD (cparraherran@med.miami.edu); Monica T. Garcia, MD; Pablo Bejarano, MD; Phillip Ruiz, MD. Department of Pathology, University of Miami-Jackson Memorial Hospital, Miami, Fla.

Context: Posttransplant lymphoproliferative disorder (PTLD) is a lifethreatening complication that ranges from reversible lymphoplasmacytic hyperplasia to frank lymphoma. Histologically, PTLD can present as subtle architectural and morphologic changes that can be easily overlooked. We reviewed the histomorphologic features, molecular studies, and related factors of PTLD.

Design: We retrospectively reviewed, during a 3-year period, biopsies from patients who underwent multivisceral/intestinal transplant and were clinically or histologically suspicious for PTLD. The biopsies were assessed for intensity of lymphoplasmacytic infiltrate, mucosal architecture, immunostains for lymphocytes, in situ hybridization for Epstein-Barr virus (EBV)-encoded RNA (EBER), and polymerase chain reaction for EBV, T-, and B-cell gene rearrangement. We also collected data such as prior treatment with OKT3.

Results: Of 805 biopsies collected, 55 biopsies from 34 patients were evaluated. According to World Health Organization classification, 28 biopsies were suspicious for PTLD, 9 showed early PTLD, 13 showed polymorphic PTLD, and 5 showed monomorphic PTLD (Table). Overall, 91% of the biopsies showed moderate to severe lymphoplasmacytic infiltrate. EBV positivity by EBER or polymerase chain reaction at the time of the biopsy or within the following month was observed in 74% of the biopsies. Fifteen cases showed B monoclonality, and 2 showed T monoclonality. Interestingly, the monoclonal findings did not correlate with the immunohistochemical stains. Nine of 17 patients diagnosed as having definitive PTLD received OKT3 prior to the diagnosis.

Conclusions: The majority of the PTLD cases demonstrated amoderate to severe lymphoplasmacytic infiltrate. However, in the presence of any lymphoplasmacytic hyperplasia and if clinically indicated, EBV and molecular studies for antigen receptor rearrangement are necessary.

Solid Pseudopapillary Tumor of the Pancreas

(Poster No. 29)

Christina J. Tatum, MD (christina.tatum@bhsala.com); Matthew V. Sheffield, MD. Department of Pathology, Baptist Health System, Birmingham, Ala.

Solid pseudopapillary tumor is a rare neoplasm of the pancreas that primarily affects young women. It is considered to be a low-grade malignant tumor that can be asymptomatic for years. Characteristic morphologic features include the formation of a solid mass composed of polygonal cells surrounding delicate blood vessels, frequent cystic degeneration, and intracystic hemorrhage. Most cases are cured by surgical resection and show a favorable prognosis; however, it tends to behave more aggressively in the male sex and in older patients. We present a 78-yearold man with a 3.7-cm complex lesion in the tail of the pancreas found incidentally on an abdominal computed tomography scan for the evaluation of hydronephrosis. He subsequently underwent distal pancreatectomy and splenectomy. Macroscopic examination demonstrated an encapsulated lesion with solid and cystic components, friable necrotic material, and remote hemorrhage. Histologically, a neoplasm with solid areas, cystic spaces, and pseudopapillae was identified. Immunohistochemical staining was positive for β-catenin, CD10, and progesterone receptor, with negative staining for chromogranin and synaptophysin, confirming the diagnosis of a solid pseudopapillary tumor. Although rarely seen, it is important to consider the diagnosis in older male patients.

Mesenchymal Transition in Pancreatic Carcinoma

(Poster No. 30)

Xiaojun Wu, MD, PhD1 (xwupath@uab.edu); Juan P. Arnoletti, MD2; Andrey Frolov, MD2; Nirag Jhala, MD.1 Departments of 1Pathology and 2Surgery, University of Alabama at Birmingham.

Context: Most pancreatic cancers are epithelial in origin. Advanced diseases have little response to current as well as new therapies such as erlotinib. Mesenchymal transition in pancreatic carcinoma cells has been implicated as being resistant to erlotinib therapy, as shown in vitro studies. Such a transition may also have implications on its metastatic potential. The objective of the study was to determine ifmesenchymal transition can be identified in human pancreatic carcinoma tissues.

Design: We prepared formalin-fixed, paraffin-embedded cell pellets from 3 pancreatic carcinoma cell lines (MIAPACA-1, Panc-1, and HPAC) and 20 sections from resected pancreatic carcinoma. The biomarkers associated with cellular mesenchymal transition, vimentin (mesenchymal, cytoplasmic stain), pancytokeratin, and E-cadherin (membranous stain), were evaluated by immunohistochemistry.

Results: MIAPACA-1 and Panc-1 demonstrated clear expression of vimentin and pancytokeratin but lacked E-cadherin. On the other hand, HPAC, a well-differentiated cell line, lacked vimentin expression with simultaneous expression of pancytokeratin and E-cadherin. All 20 (100%) cases were positive for E-cadherin. Vimentin expression was noted in 12 (60%) of 20 cases. Nine cases that demonstrated vimentin expression had positive immunoreactivity in 10% of the tumor cells. A more extensive vimentin expression was noted in 3 of 12 tumors that were positive for vimentin. These latter 3 cases demonstrated poor tumor differentiation.

Conclusions: This study demonstrates that mesenchymal transition occurs in human pancreatic carcinoma. Additional studies are needed to further characterize implications of mesenchymal transition noted in this tumor, including its potential as prognostic indicator and/or for guidance in the selection of chemotherapeutic agents.

CD138 Expression in Neoplastic and Nonneoplastic Liver: An Immunohistochemical Study

(Poster No. 31)

Bamidele A. Adeagbo, MBBS (badeagbo@mcg.edu); Preetha Ramalingam, MBBS; Jeffrey Lee, MD; Michelle Reid-Nicholson, MBBS. Department of Pathology, Medical College of Georgia, Augusta.

Context: CD138 is a heparan sulphate-rich membrane glycoprotein and a known marker of plasmacytic differentiation. It is expressed by a variety of normal tissues and epithelial tumors, including benign liver and hepatocellular carcinoma (HCC). Systematic analysis of its expression in benign chronic hepatitis C (CHC) and cirrhosis and malignant liver parenchyma has not been described.

Design: A total of 40 cases, including 14 HCCs (2 low grade and 12 high grade), 13 CHC, and 13 cirrhosis, were randomly selected and evaluated for CD138 expression (monoclonal). HCC was graded according to a 2-tier classification system of low and high grade. Staining was scored based on areas of greatest intensity. Staining distribution/intensity was recorded as follows: 0 (no staining), 1+ (<25%), 2+ (26%-50%), and 3+ (50%). Two high-grade HCCs were excluded due to loss of diagnostic material after sectioning.

Results: One case of HCC showed both low- and high-grade cytology, with 2+ staining in low-grade areas and 3+ staining in high-grade areas. Two cases of cirrhosis showed diffuse 3+ staining but were also remarkable for extensive macrovesicular steatosis (Table).

Conclusions: CD138 is expressed with distinct staining patterns by both neoplastic and nonneoplastic liver parenchyma. The benign conditions CHC and cirrhosis show low-intensity staining, while HCC shows high-intensity staining. There is no difference in staining intensity between the benign conditions CHC and cirrhosis. CD138 may potentially be a useful marker for distinguishing normal liver and nonneoplastic conditions from low-grade HCC. CD138 staining should be interpreted with caution, particularly in the presence of steatosis.

Eosinophils in Resected Colons With Hirschsprung Disease

(Poster No. 32)

Masha C. Nzabi, MD1; Vivekanand Singh, MD, FCAP2 (vsingh@cmh.edu). 1Department of Pathology, University of Missouri at Kansas City; 2Department of Pathology, Children's Mercy Hospitals and Clinics, Kansas City, Mo.

Context: Although eosinophils are frequently observed in the neural plexuses of the intestinal wall of patients with Hirschsprung disease, only a single study with 10 patients has been published.We studied 40 patients with Hirschsprung disease to characterize the eosinophil infiltration.

Design: Forty patients with Hirschsprung disease who underwent resection of their aganglionic colon were selected. The criterion for selection was to include only cases that had the entire aganglionic segment sampled and a follow-up of at least 4 months. Eosinophils in the myenteric and submucosal plexuses were counted at a total magnification of ×400 highpower fields in contiguous fields along the length of the specimen. The duration between the diagnostic biopsy and resection of aganglionic segments was recorded. The date of colostomy, if performed, and outcome were recorded.

Results: The results are summarized in the Table. In all cases, the eosinophil infiltration density was nearer to the ganglionic/aganglionic transition zone.

Conclusions: Our findings confirm that patients with Hirschsprung disease have an infiltration of myenteric and submucosal plexuses by eosinophils, which is more apparent near the ganglionic-aganglionic transition area. With increasing duration of interval from biopsy diagnosis to resection, there is a progressive decline in the eosinophils, most obviously in patients receiving colostomy before resection. There was no correlation between outcome, either good or complicated, with the eosinophil density in neural plexuses.

Persistence of Normal Numbers of Interstitial Cells of Cajal in Longitudinal Muscle Layer of Colon Increases Likelihood of Postsurgical Complications in Hirschsprung Patients

(Poster No. 33)

Vivekanand Singh, MD, FCAP (vsingh@cmh.edu). Department of Pathology, Children's Mercy Hospitals and Clinics, Kansas City, Mo.

Context: A high number of patients with Hirschsprung disease (HSCR) who undergo surgical resection present with complications of bowel movement. As the interstitial cells of Cajal (ICC) are known to be altered in HSCR, we examined the association of ICC with outcome of surgery.

Design: Forty postsurgical HSCR patients who were followed up for more than 4 months were selected. Immunohistochemistry for ICC was performed on sections of aganglionic and ganglionic colonic wall using c-kit antibody, and the immunostained sections were semiquantitatively scored. A decrease of more than 33% was recorded as decreased. The normal was determined from 20 control colons obtained at autopsy from children who had no gastrointestinal disease and no metabolic or chromosomal disorders. The outcome of surgery was recorded as good or complicated (fecal soiling/constipation/enterocolitis).

Results: The aganglionic segment showed decrease of ICC in circular muscle in most cases and a decrease in Auerbach plexus and longitudinal muscle in 45% of cases. The ganglionated segment showed a decrease in ICC of circular muscle in most cases and of Auerbach plexus in 40% of cases. The longitudinal muscle showed normal ICC in 20% of cases. More patients with complicated outcome (46%) had normal ICC in longitudinal muscle than patients with good outcome (7%), with an odds ratio of 10.7 (CI = 2-65; P = .01). Outcome was not related to ICC in Auerbach plexus or circular muscle.

Conclusions: Presence of normal ICC numbers in longitudinal muscle of resected colons may increase the likelihood of fecal soiling (probably due to distally propagating peristaltic waves) in postsurgical HSCR patients.

Single-Nucleotide Polymorphisms in Crohn Disease

(Poster No. 34)

Amanda L. Peterson, MD (amanda.l.peterson@uth.tmc.edu); Dwight Oliver, MD. Department of Pathology, University of Texas Health Science Center-Houston.

Context: Environmental and genetic factors are theorized to play a role in the complexity of Crohn disease. A recent genome-wide analysis for single-nucleotide polymorphisms (SNPs) revealed 11 loci that were highly associated (P < 10^sup -7^ or less) with Crohn disease. Because Crohn disease typically cannot be differentiated from ulcerative colitis on histology alone, we wished to test the feasibility of using SNP analysis to assist in the clinical and histologic differentiation of these 2 diseases on initial biopsy specimens.

Design: We reviewed 120 Crohn disease, ulcerative colitis, and noninflammatory colitis cases and chose 25 with the most reliable clinicopathologic diagnosis and available archival tissue. We then designed allelespecific oligonucleotide primers for 11 previously described SNPs (including NOD2, IL23R, and loci within 3p21, 10q24.2, and others) for use in optimized polymerase chain reaction genotyping assays. DNA was isolated from paraffinized tissue of the colitis patients and genotyped for the SNPs. Amplicons were analyzed by agarose gel electrophoresis.

Results: Patients were successfully SNP genotyped with our assay, and differences were found between the 3 diseases. Odds ratios were calculated and correlated with the clinicopathologic diagnosis of each patient. Allele-type trends were complex. No individual SNP could differentiate the 3 diagnoses.

Conclusions: Laboratory SNP analysis may have a role in assisting in the routine clinical differentiation of patients with inflammatory bowel disease prior to colectomy.

Mature Cystic Teratoma Separately Involving the Appendix and Ovary: A Case Report and Review of the Literature

(Poster No. 35)

Rania Bakkar, MD (hananλfarghaly@yahoo.com); Gwendolyn J. Godfrey, DO; Hanan Farghaly, MD. Department of Pathology, University of Louisville, Louisville, Ky.

Mature cystic teratoma is a benign tumor of germ cell origin that most commonly arises in gonads. The appendix is considered one of the rare sites of occurrence for this tumor. To our knowledge, this is the third case to be reported of mature cystic teratoma arising in the appendix. In the other 2 cases, one presented with acute appendicitis, and the second presented with a painless abdominal mass. We report a case of mature cystic teratoma arising separately in the right ovary and appendix in a 38-yearold woman who presented with a painless abdominal enlargement that was presumed to be an enlarged uterus. The patient was scheduled for an exploratory laparotomy. Intraoperatively, 2 masses were separately identified and were 5 cm apart. The right ovarian mass measured 8 cm, and an appendiceal mass measured 6 cm. Sectioning of the ovarian and appendiceal masses revealed a cystic lesion filled with yellow cheesy substance along with hair and teeth. Microscopic examination of the appendix revealed an encasing cystic mass of the appendix that contained keratinous material and was lined by stratified squamous epithelium with sebaceous glands. In conclusion, mature cystic teratoma is a rare tumor of the appendix; however, it should be considered in the differential diagnosis of cystic lesions of the appendix. In our case, the pathologic features were typical of mature cystic teratoma in 2 separate locations, the ovary and the appendix. The latter of which is only the third such case described in the literature.

A Novel Molecular Grading System Predicts Prognosis of Human Hepatocellular Carcinoma

(Poster No. 36)

Pal Kaposi-Novak, MD, PhD (kaposinovakp@upmc.edu); George K. Michalopoulos, MD, PhD. Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pa.

Context: Conventional histologic parameters do not correlate with prognosis of human hepatocellular carcinoma (HCC). Genomic profiling could be utilized to construct alternative classification systems.

Design: We performed meta-analysis of global gene expression data from 101 human HCC samples. A 583-gene signature showing cell cycle-dependent induction was determined in synchronized HeLa cells. Fiftytwo genes specifically expressed in fully differentiated hepatocytes were selected with digital differential display and through literature search. Histologic grades were determined according to the Edmondson system. Proliferation index was calculated after Ki-67 immunohistochemistry.

Results: We assessed expression of predefined proliferation and differentiation-specific gene sets in human HCC. Differentiation and proliferation scores of 60 tumors in the training set were calculated from rank averages of signature genes. Based on the combined scores, tumors were proportionally divided into 3 molecular grades (MG1 to MG3). Highgrade tumors were characterized by increased expression of the proliferation and low expression of the liver-specific genes. We used 6 prediction algorithms to determine genes (SAA4, APCS, MCM6, etc) that can optimally diversify HCC into molecular grades. Combined expression ratios of the classifier genes were used to assign grades to 41 tumors in the validation set. The histologic grade did not correlate with (r = 0.21) the predicted molecular grade or with the prognosis. However, higher molecular grades showed significant association (log-rank, P = .02) with decreased survival (MG1, 140 ± 12.5; MG2, 55.6 &plusmn 25.08; MG3, 9.16 ± 5.79 months).

Conclusions: A novel gene expression-based grading system could be successfully applied to predict prognosis of human HCC.

Clear Cell Change in Gastric Biopsies

(Poster No. 37)

Joe K. Lennerz, MD (JLennerz@path.wustl.edu); Elise L. Krejci, MD; Emily A. Bantle, MD; Jim S. Lewis Jr, MD. Department of Pathology, Washington University, St Louis, Mo.

Context: Clear epithelial cells are frequently seen in gastric biopsies but are seldom mentioned. Distinct from endocrine cells and the other 4 principal cellular constituents, clear cell change (CCC) is a confusing finding. When clustered or crowded, it may mimic adenocarcinoma, a pattern previously described as clear cell degeneration. The association of CCC with Helicobacter pylori (HP), gastritis, or intestinal metaplasia (IM) is unknown.

Design: To study the association of CCC with gastritis and/or HP, 164 gastric biopsies (age range, 2-87 years; mean age, 53 years; 76 males), all evaluated by Steiner staining, were selected as consecutive cases from our files. CCC was graded as follows: 0 = absent; 1 = single; 2 = clustered.

Results: CCC (Figure 20, bar = 50 µm), which was present in 42 (26%) cases, was not associated with age, sex, or gastric subsite. We found significant association of CCC with chronic gastritis, 20 of 69 (χ^sup 2^ = 9.61; P = .048). Six of the 12 cases with normal mucosa and 3 of the 10 cases with IM showed CCC (no correlation, χ^sup 2^ = 3.21). Blinded reinterpretation of Steiner stains showed HP in 30 cases, and 6 showed CCC. In 35 of the HP-negative cases, CCC was present, and the difference was not significant (χ^sup 2^ = 0.49).

Conclusions: CCC is indeed a frequent finding in gastric biopsies and is associated with chronic gastritis but not with HP or IM. The nature of this mucosal response is unknown; however, the practicing pathologist should be aware of this finding. When encountered, the differential diagnosis for CCC should include aging change, artifact, chronic gastritis, and adenocarcinoma.

Proteomic Expression Analysis of Surgical Human Colorectal Cancer Tissues by Tandem Mass Spectrometry: Upregulation of PSB7, PRDX1, and SRP09 and Hypoxic Adaptation in Cancer

(Poster No. 38)

Michael H. Roehrl, MD, PhD1 (michaelλroehrl@hms.harvard.edu); Jung-Hyun Rho, PhD2; Julia Y. Wang, PhD.2 1Department of Pathology, Massachusetts General Hospital, Boston; 2Department of Medicine, Brigham and Women's Hospital, Boston, Mass.

Context: Colorectal adenocarcinoma is one of the leading causes of cancer deaths worldwide. Discovery of specific biomarkers for early detection and identification of underlying pathogenetic mechanisms is important. Global proteomic approaches have thus far been limited by the large dynamic range of molecule concentrations in tissues and the lack of selective enrichment of the low-abundance proteome.

Design: We studied paired cancerous and normal clinical tissue specimens from patients with colorectal adenocarcinomas by heparin affinity fractionation enrichment followed by 2-dimensional polyacrylamide gel electrophoresis and tandem mass spectrometric identification.

Results: Fifty-six proteins were found to be differentially expressed, and of these, 32 low-abundance proteins were only detectable after heparin affinity enrichment. Tandem mass spectrometry was used to identify 5 selected differentially expressed proteins as proteasome subunit β type 7 (PSB7), hemoglobin α subunit (HBA), peroxiredoxin 1 (PRDX1), argininosuccinate synthase (ASSY), and signal recognition particle 9 kDa protein (SRP09). This is the first proteomic study detecting the differential expression of these proteins in human colorectal cancer tissue. The relative specificities of PSB7, PRDX1, and SRP09 overexpression in colon cancer were validated by Western blot analysis of patients with colon adenocarcinomas. Overexpression of the 3 proteins was restricted to the neoplastic cancer cell population within the tumors, demonstrating both cytoplasmic and nuclear localization of PSB7 and predominantly cytoplasmic localization of PRDX1 and SRP09.

Conclusions: We describe heparin affinity fractionation enrichment as a prefractionation tool for the study of the human primary tissue proteome and for the discovery of PSB7, PRDX1, and SRP09 upregulation as new biomarkers for colon cancer.

Protein Expression Profiling of Irinotecan Pathway in Colorectal Cancer

(Poster No. 39)

Wanghai Zhang, MD, PhD1 (wayne805@hotmail.com); Mark A. Watson, MD2; Howard L. McLeod, PharmD.3 1Department of Pathology,Howard University Hospital, Washington, DC; 2Department of Pathology, Washington University School of Medicine, St Louis, Mo; 3Department of Pharmacogenomics and Individualized Therapy, University of North Carolina, Chapel Hill.

Context: The exact mechanism for variation of response to chemotherapy remains unclear. Individualized therapy strategies for cancer will require a more thorough understanding of the pathways influencing drug fate, including expression of cellular target enzymes, metabolism enzymes, and cellular transporters. Irinotecan is an excellent example of an anticancer drug in need of individualization. We profile expression of proteins in an irinotecan pathway in colorectal cancer tissues and construct a new pharmacologic pathway to help advance individualization in the selection of cancer therapy.

Design: Paired tumor and normal tissues from 52 patients with Dukes C colorectal cancers were used to construct a tissue microarray. Fifteen markers, including CES2, NF-κB, XRCC1, CDC45, TDP1, TOP1, PARP1, ABCC1, ABCC2, ABCC3, ABCB1, ABCG2, p53, ERCC2, and UGT1A1, that are related to the irinotecan pathway were immunohistochemically stained on the tissue microarray. Protein expression was assessed to derive an overall expression level. Hierarchical clustering was used with unsupervised algorithms to identify patterns of protein expression that produced distinct clusters of patients.

Results: The relative expression levels across the 15 pathway proteins and the interpatient variabilities were considerable. Using hierarchical clustering, 3 protein clusters and 3 patient groups had highly similar indices based on the protein expressions in colorectal tumors. The 3 patient groups had no unique clinical pathologic features but could be differentiated by the statistically significant differences in the protein expression levels of 4 proteins.

Conclusions: Our study indicates that gene expression profiling could be valuable for predicting tumor response to chemotherapy and for tailoring therapy to individual cancer patients.

Comparison of Central HER-2 Tests With Quantitative HER-2 Expression and HER-2 Homodimer Measurements Using a Novel Proximity-Based Assay

(Poster No. 40)

Weidong Huang, MD, PhD1 (weidong.huang@monogrambio.com); Monica Reinholz, PhD2; Jodi Weidler, PharmD1; Yolanda Lie, MS1; Yi-Chen Wu, MS1; Colombe Chappey, PhD1; Jeannette Whitcomb, PhD3; Wilma Lingle, PhD4; Robert Jenkins, MD, PhD4; Jeffrey S. Larson, PhD3; Yuping Tan, MS3; Michael Bates, MD1; Edith A. Perez, MD.4 Departments of 1Clinical Research and 3Clinical Laboratory Operation, Monogram Biosciences, Inc, South San Francisco, Calif; 2Departments of Experimental Pathology and Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, Minn; 4Department of Medicine,Mayo Clinic, Jacksonville, Fla.

Context: The accuracy and reliability of standard methods, immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) to assess HER-2 status has recently been a subject of debate. We developed a novel assay (HERmark, Monogram Biosciences, Inc, South San Francisco, Calif) that provides precise quantification of HER-2 expression (H2T) and homodimerization (H2D) in formalin-fixed, paraffin-embedded (FFPE) tissues. We compared H2T and H2D generated by HERmark to Central Laboratory's (Mayo Clinic, Rochester, Minn) HER-2 IHC and FISH results.

Design: H2T and H2D were detected through light-dependent release of fluorescent tags (VeraTags, Monogram Biosciences) conjugated to a HER-2 antibody, requiring proximity to a second HER-2 "scissors" antibody. The VeraTag signal was quantified by capillary electrophoresis and was normalized to tumor area. Assay comparison correlated H2T and H2D with Central Laboratory's HER-2 IHC of 153 FFPE breast cancers and HER-2 gene amplification by FISH in a subset of the cases.

Results: H2T in the 153 breast cancers described a continuum along a wide dynamic range (>2 log), in contrast to conventional IHC categories. The correlation between H2T and IHC categories was significant (P < .001). Overlap of H2T among the IHC categories was observed. H2D showed a general correlation with H2T (P < .001). HER-2 gene amplification correlated well with IHC categories and H2T values in 9 available cases. Exploratory analyses for a cut-off value for H2T were performed.

Conclusions: VeraTag assay reliably measures H2T and H2D in FFPE tissues. H2T was generally concordant with Central Laboratory HER-2 tests. The precise quantification of H2T and the novel H2D measures may provide better predictive tests for targeted HER-2 therapy.

Financial Disclosure: Weidong Huang, MD, PhD; Jodi Weidler, PharmD; Yolanda Lie, MS; Yi-Chen Wu, MS; Colombe Chappey, PhD; Jeannette Whitcomb, PhD; Jeffrey S. Larson, PhD; Yuping Tan, MS; and Michael Bates, MD, own stock in Monogram Biosciences, Inc.

Evaluation of a Multiplexed Methylation-Specific Polymerase Chain Reaction-Based Urine Assay to Aid in Diagnosis of Prostate Cancer

(Poster No. 41)

Jonathan Baden, MSc1 (jbaden@vrxus.jnj.com); George Green, PhD1; Jennifer Painter, MSc1; Kathleen Curtin, MSc1; Jadwiga Markiewicz, MSc1; Jennifer Jones, BSc1; Tara Astacio, BSc1; JyotiMehrotra, PhD1; Jedidiah Quijano, BSc1; Wilson Guinto, BSc1; Bradley C. Leibovich, MD2; Yixin Wang, PhD1; Wuxiong Cao, PhD.1 1Technology Development, Veridex, LLC,Warren, NJ; 2Department of Urology, Mayo Clinic, Rochester, Minn.

Context: This study describes a multicenter evaluation of a prototype assay for the detection of prostate cancer (Veridex, LLC, Warren, NJ), while minimizing unnecessary biopsies in men with prostate-specific antigen (PSA) levels from 2.0 to 10.0 ng/mL.

Design: The investigational assay is based on a methylation-specific polymerase chain reaction to detect methylated cytosines within the promoter regions of 3 markers, glutathione S-transferase P1, retinoic acid receptor β2, and adenomatous coli polyposis, that are indicative of the presence of prostate cancer. The prototype assay was evaluated with urine samples collected at 9 clinical sites after a digital rectal examination was conducted on 175 (83 cancer and 92 noncancer) patients with PSA levels from 2 to 10 ng/mL.

Results: Assay sensitivity of 59% and specificity of 80% were observed for detection of prostate cancer as compared with histologic results of biopsy tissue. A logistic regression algorithm using 3 markers, glutathione S-transferase P1, retinoic acid receptor β2, and adenomatous coli polyposis, resulted in an area under the curve value of 0.72. A logistic regression algorithm using PSA, digital rectal examination results, and age of the patient produced an area under the curve of 0.59. This increase in observed performance was statistically significant (P = .03). Moreover, positive predictive value of the prototype assay improved when having 1 (50%), 2 (73%), or 3 (88%) positive markers.

Conclusions: Using this prototype assay, detection of prostate cancer was significantly better than when using PSA, age, and digital rectal examination results alone. Consequently, screening for prostate cancer may be made more efficient and effective with incorporation of such an assay into current screening algorithms.

Financial Disclosure: Jonathan Baden, MSc; George Green, PhD; Jennifer Painter, MSc; Kathleen Curtin, MSc; Jadwiga Markiewicz, MSc; Jennifer Jones, BSc; Tara Astacio, BSc; Jyoti Mehrotra, PhD; Jedidiah Quijano, BSc; Wilson Guinto, BSc; Yixin Wang, PhD; and Wuxiong Cao, PhD, own stock in Veridex, LLC.

Efficacy of RNase Inhibitors to Preserve RNA in Colon Cancer Tissue for Laser Capture Microdissection

(Poster No. 42)

John Gillespie, MD1 (jgill@mail.nih.gov); Helen Zhou, BS2,3; Lena Diaw, PhD1; Hien Dang, BS2,3; Helen Moore, PhD2,3; Jim Robb, MD, FCAP3; Jim Vaught, PhD3; Carolyn Compton, MD, PhD.3 1Science Applications International Corporation-Frederick, Inc, and National Cancer Institute at Fredrick, Md; 2Biospecimen Research Network and 3Office of Biorepositories and Biospecimen Research, National Cancer Institute, Bethesda,Md.

Context: Laser capture microdissection allows procurement of pure populations of cells from tissue. Because RNA is very labile, a frequent question from investigators is the maximum amount of time they have to complete microdissection. The staining process may lead to the greatest loss of RNA, due to endogenous RNases that are activated in aqueous environments. This study compares the efficacy of 3 RNase inhibitors to preserve RNA in tissue for laser capture microdissection.

Design: Tissue sections of anonymized frozen colon cancer were hematoxylin-eosin stained with and without RNase inhibitor using 1 of 3 different inhibitors: ProtectRNA (Sigma Aldrich, St Louis, Mo), Protector RNase (Roche, Indianapolis, Ind), or RNase Inhibitor (Qiagen, Valencia, Calif). Fifteen thousand cells were microdissected after being at ambient temperature for 0, 2, 24, and 48 hours. RNA was extracted, quantitated, and its quality determined by 28S:18S ratio, RNA integrity number, and quantitative reverse transcription-polymerase chain reaction for the ratio of Cts for 3' and M primer sets.

Results: There was essentially no difference in the quantity of RNA recovered from all samples. RNA quality was excellent at 0 and 2 hours with and without RNase inhibitor treatment. After 24 hours, the highest quality RNA was with ProtectRNA. After 48 hours, all samples had poor quality RNA.

Conclusions: These findings suggest that quality RNA, useful for gene expression analysis, can be obtained by microdissection at ambient temperature for up to 2 hours without RNase inhibitor and up to 24 hours with ProtectRNA from colon cancer slides.

POSTER SESSION 300: FRIDAY, SEPTEMBER 26, 2008, 10:00 AM-12:30 PM

Kidney and Genitourinary Pathology; Bone and Soft Tissue Pathology; Autopsy and Forensic Pathology; Cardiovascular Pathology

A Unique Staining Pattern of CD10 in Primary and Metastatic Seminoma of the Testis

(Poster No. 1)

Dian Feng, MD1 (dianfeng@buffalo.edu); Shaozheng Zhang,MD.2 1Department of Pathology, State University of New York at Buffalo, East Amherst; 2Department of Pathology, Roswell Park Cancer Institute, Buffalo, NY.

Context: CD10 antigen is a zinc metalloendopeptidase expressed in a variety of normal and neoplastic lymphoid and nonlymphoid tissues.Two immunohistochemical staining patterns for CD10 on the cytoplasmic membrane and occasionally in the Golgi zone have been demonstrated. However, the expression of CD10 in primary and metastatic seminoma of the testis has not been reported.

Design: Paraffin-embedded, formalin-fixed tissue sections from 8 cases of primary seminoma and 2 cases of metastatic seminoma of the testis were stained with antibody for CD10 by immunohistochemical method. Four cases of primary carcinoma of the testis and 7 cases of metastatic embryonal carcinoma of the testis, as well as 20 cases of metastatic renal cell carcinoma, were also stained for CD10.

Results: A unique staining pattern with distinct paranuclear dots in the Golgi zone (Figure 21) was present in the cytoplasm of the primary and metastatic seminoma. In contrast, all of the primary and metastatic embryonal carcinomas of the testis were negative for CD10, whereas all of the metastatic renal cell carcinomas demonstrated the conventional cytoplasmic membrane staining for CD10.

Conclusions: CD10 was positive in all of the primary and metastatic seminomas of the testis and negative in all of the embryonal carcinomas of the testis. The unique staining pattern for CD10, with distinct paranuclear dots in the Golgi zone, may be useful for differential diagnosis of seminoma from embryonal carcinoma and renal cell carcinoma. CD10 may be used as a new marker for primary and metastatic seminoma of the testis.

Aminopeptidase N Expression Is an Indicator of Aggressive Behavior in Renal Cell Carcinoma

(Poster No. 2)

Redouane Boumendjel, MD1 (rboumendjel@sbcglobal.net); SwatiMehrotra, MD1; Antonella Lostumbo, MD1; Alexis Chesrow, MD2; Suman Setty, MD.1 Departments of 1Pathology and 2Surgery, University of Illinois at Chicago.

Context: The incidence of aggressive renal cell carcinoma (RCC) is on the rise in the United States. We studied 2 markers of importance in tumor metastasis, aminopeptidase N (APN), a neutral endopeptidase, andmatrix metalloproteinase (MMP-9) to correlate aggressive tumor behavior with levels of protein and transcript expression.

Design: RCCs (n = 64) of clear, papillary subtypes were selected. Tumors 7 cm or larger, Fuhrman nuclear grade 2 or greater, organ or lymph node metastasis, and renal vein invasion (stage ≥2) were classified as high grade (n = 33); tumors lacking these features were classified as low grade (n = 31). A tissue microarray of 46 tumors (high grade, n = 23; low grade, n = 23) was constructed by sampling tumor center and periphery and was analyzed with antibody to APN (1:100; Santa Cruz Biotechnology, Calif). Additionally, real-time polymerase chain reaction studies for levels of MMP-9 and APN were done on 18 paired tumors and adjacent normal kidney tissues. Statistical calculations were performed using Student t test.

Results: The average ratio of tumor to normal APN and MMP-9 RNA transcripts (Table 1) and APN protein expression at periphery/invasive tumor front versus the tumor center (Table 2) were tabulated.

Conclusions: The average ratio of tumor to normal APN RNA transcript expression was significantly higher in high-grade RCC, unlike MMP-9 RNA. Protein expression of APN in the tissue microarray was similarly greater in high-grade RCC, with statistically significant increase at the tumor periphery/invasive front. Thus, APN transcript abundance is better at discriminating aggressive behavior in RCC than the previously described MMP-9.

Morphologic, Cytogenetic, and Molecular Analysis of Renal Cell Carcinomas With a Prominent Rhabdoid Phenotype

(Poster No. 3)

Aleksandr M. Perepletchikov, MD, PhD (perepletchikova@upmc.edu); Rajiv Dhir, MD; Guoping Cai, MD; Sheldon Bastacky, MD; Anil V. Parwani, MD, PhD. Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pa.

Context: Renal cell carcinoma (RCC) with sarcomatoid features comprises approximately 5% of conventional type RCCs. In this study, we characterized a series of RCCs with prominent rhabdoid histology (predominant morphologic pattern or a component of mixed morphology tumors) using immunohistochemistry, cytogenetics, and loss of heterozygosity.

Design: A search of the pathology files at our institution for RCC cases with sarcomatoid morphology and rhabdoid differentiation from a 3-year period was performed. These cases were characterized by light microscopy, immununohistochemistry (CD10, vimentin, RCC antigen, cytokeratin 7), fluorescence in situ hybridization (probes CEP1, CEP7, and CEP17 for corresponding chromosomes), and loss of heterozygosity [von Hippel-Lindau gene, gene locus (3p25-3p26)].

Results: A total of 12 RCC cases with rhabdoid-type morphology were examined. The patients were 4 women and 8 men ranging in age from 48 to 88 years (mean, 68 years). The tumor size ranged from 3.7 to 17 cm (mean, 7.2 cm). Histologically, the tumors demonstrated prominent rhabdoid morphology with other subcomponents, including conventional, papillary, spindle cell, and mucinous components. Eight patients (67%) were diagnosed with T3 stage RCC. Only one patient tested positive for loss of heterozygosity von Hippel-Lindau gene. All studied neoplasms showed multiple ploidy changes in examined chromosomes (Table).

Conclusions: Comprehensive review of sarcomatoid RCCs with rhabdoid features revealed that a subset of these tumors might have specific cytogenetic and molecular changes. Interestingly, most neoplasms are not related to conventional type RCCs and should be subclassified as RCC, unclassified. Additional studies such as single nucleotide polymorphism analysis may be valuable to further characterize these tumors.

The Distribution of PAX-2 Immunoreactivity in Seminal Vesicle, Ejaculatory Duct, Prostatic Urethra, Normal Prostate Glands, and Prostatic Adenocarcinoma: Potential Implications for Diagnostic Usage

(Poster No. 4)

Abstract Withdrawn

A Limited Immunohistochemical Panel of Cytokeratin, Synaptophysin, and p63 Discriminates Small Cell Carcinoma From High-Grade Urothelial Carcinoma of the Urinary Bladder

(Poster No. 5)

Sherry M. Thompson, MD (smthompson78@hotmail.com); Carmen Gomez-Fernandez, MD; Aldo Mejias, Jr, MD; Merce Jorda, MD. Department of Pathology, Jackson Memorial Hospital/University of Miami Miller School of Medicine, Miami, Fla.

Context: Small cell and high-grade neuroendocrine carcinomas (SCC/HGNECs) of the urinary bladder are uncommon but highly aggressive neoplasms. Differentiation of SCC/HGNEC from high-grade urothelial carcinoma (UC) is based on histomorphologic features and it may become difficult with small biopsies. We attempt to identify an immunohistochemical panel that differentiates SCC/HGNEC from high-grade UC.

Design: We selected 37 samples from 34 patients with bladder carcinoma with small cell morphology (13 SCC/HGNECs, 24 high-grade UCs); 3 neoplasms showed mixed histologic pattern (SCC/HGNEC with UC). The samples were obtained by cystectomy (23) or biopsy/transurethral resection (11) at our institution between 2003 and 2007. Immunohistochemistry for pancytokeratin (CK), synaptophysin (SYN), p63, and thyroid transcription factor 1 (TTF-1) was performed in all samples using the L-SAB method (L-SAB kit, Universal K0690, Dako, Carpinteria, Calif).

Results: Immunohistochemistry for CK was positive in all but 1 (12/13) SCC/HGNEC and showed a characteristic punctate cytoplasmic staining pattern. All were positive for SYN and negative for p63. All 24 highgrade UCs showed diffuse cytoplasmic and membranous staining for CK and were negative for SYN. Of these neoplasms, 19 (79%) were positive for p63. All 37 samples were nonreactive for TTF-1.

Conclusions: A limited immunohistochemical panel including CK, SYN, and p63 discriminates SCC/HGNEC from high-grade UC. The punctate cytoplasmic pattern of CK staining is specific for SCC/HGNEC. Positivity for SYN and negativity for p63 supports the diagnosis of SCC/HGNEC. Diffuse cytoplasmic and membranous staining for CK and negativity for SYN characterizes high-grade UC. TTF-1 positivity was not seen in any of the SCC/HGNECs.

Seasonal Variations of Lupus Nephritis

(Poster No. 6)

Steven Vanderwerf, MD1; Jared L. Schmidt, MD1 (schm1911@umn.edu); Bradley M. Linzie, MD2; John T. Crosson, MD2; Gretchen S. Crary, MD.2 1Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis; 2Department of Laboratory Medicine and Pathology, Hennepin County Medical Center, Minneapolis, Minn.

Context: Several autoimmune diseases have demonstrated seasonal variation, including systemic lupus erythematosus. Lupus patients have shown summer increases in photosensitive rashes, winter increases in joint pain, and a higher prevalence of class V lupus nephritis (LN) in the spring and winter. Our goal is to determine if seasonal changes in LN are more or less prominent in the Midwest.

Design: Data on histopathologic class and patient characteristics were collected on all native kidney biopsies diagnosed with LN from January 1, 2005 through December 31, 2007. We identified 139 cases of LN and grouped them for comparison by the season during which the biopsy was performed. The seasons were designated as spring (April 22-June 21), summer (June 22-September 21), fall (September 22-December 21), and winter (December 22-March 21). Cases with membranous LN were counted in 2 groups if another class lesion was present.

Results: There were 41, 38, and 60 LN biopsies from 2005, 2006, and 2007, respectively. The average age was 34.9 years with an F/M ratio of 5.8:1. The peak month for diagnosis of classes II, III, and V was summer and class IV was spring (Table). There were no significant differences between the LN classes by season.

Conclusions: Results show a trend toward a higher prevalence of class IV LN in the winter and spring (P = .06), which was not seen in a recent study comparing seasonal variation. We did not observe a significant increase in class III and V during the winter and spring as previously reported.

Minimal or No Residual Prostatic Adenocarcinoma on Radical Prostatectomy

(Poster No. 7)

Ognjen Kosarac, MD1 (okosarac@tmhs.org); Alberto G. Ayala, MD.2 1Department of Pathology, The Methodist Hospital, Houston, Tex; 2Department of Pathology, The Methodist Hospital, Weill Medical College of Cornell University, Houston, Tex.

Context: A vanishing cancer on radical prostatectomy after a positive prostate biopsy is reported in less than 0.5% of cases.

Design: Our database (2004-2008) on radical prostatectomy yielded 7 "vanishing carcinomas" and 1 case with a 1-mm carcinoma (Ca). The initial step was to obtain 3 levels of all blocks. In the absence of tumor, the paraffin blocks were melted, the tissue was flipped, and 3 levels were prepared. The frozen tissue for the tumor bank was processed for routine examination.

Results: Seven of 8 cases revealed absence of Ca. The eighth case showed a 1-mm focus of Ca; because of the size of the Ca, the tissues were processed as in the other 7 cases. Following block recuts, Ca was identified in 6 of 7 cases. Ca ranged in size from 1 to 4.2 mm. In 2 of 6 cases, Ca was found in the tumor bank tissue. In 1 case, there was no evidence of Ca, and instead, only multifocal high-grade prostatic intraepithelial neoplasia. In the case with a 1-mm focus of Ca, 2 foci of tumor (<1 mm each) were found.

Conclusions: In radical prostatectomy with "vanishing cancer," we recommend the following: obtain 3 levels of each paraffin block; when negative for tumor, melt and flip the paraffin blocks and prepare 3 levels; frozen tissue for research must be retrieved and processed for routine examination. Our data indicate that by following the previously mentioned guidelines, a hidden carcinoma may be detected in most cases.

Malignant Mesothelioma of the Tunica Vaginalis

(Poster No. 8)

Ji-Weon Park, MD1 (jiwpark@notes.cc.sunysb.edu); Yefim Sheynkin, MD2; Seth Klein, MD3; Jingxuan Liu, MD.1 Departments of 1Pathology, 2Urology, and 3Radiology, Stony Brook University Medical Center, Stony Brook, NY.

Malignant mesotheliomas are rare malignancies that are most often found in the pleural and peritoneal cavities. Those that affect the paratesticular region account for less than 1% of all mesotheliomas. We report a case of malignant mesothelioma of the tunica vaginalis in a 66-year-old man with a history of asbestos exposure occurring 20 years ago. He presented with bilateral chronic hydroceles secondary to previous vasectomy procedure at 38 years of age. Ultrasound and magnetic resonance imaging revealed a left paratesticular cystic mass with at least 2 enhancing papillary fronds projecting from the cyst wall. The patient underwent excision of the cystic mass and left orchiectomy. The hydrocele, measuring 12 × 2.8 cm, had a smooth outer surface, a thickened cyst wall, and multiple polypoid nodular excrescences (measuring 1.5 cm in greatest dimension). Microscopy revealed exophytic papillary structures with complex fibrovascular cores lined by mesothelial cells and infiltrating tubules with associated fascicles of atypical elongated spindle cells. The cells were pleomorphic with irregular hyperchromatic nuclei and prominent nucleoli. Immunohistochemical staining was positive for calretinin (nuclear and cytoplasmic), cytokeratin AE1/AE3, and WT-1 but was negative for B72.3 and Ber-Ep4. Although the link between prior exposure to asbestos and malignant mesotheliomas has been established, other possible associations, such as chronic irritation resulting from hydroceles, could be a contributing factor as well. To our knowledge, this is the first case of malignant mesothelioma of the tunica vaginalis presenting with a history of previous vasectomy.

Proteinuria in Diabetic Glomerulosclerosis: Can the Degree of Proteinuria Predict the Presence of Concurrent Glomerulopathy and/or the Severity of Diabetic Glomerulopathy?

(Poster No. 9)

Wei Li, MD (Wei.Li@uth.tmc.edu); Regina Verani, MD. Department of Pathology and Laboratory Medicine, The University of Texas Medical School at Houston.

Context: In patients with diabetic glomerulopathy (DG), heavy proteinuria may reflect the presence of concurrent glomerulopathy (CG). This study aims to evaluate if degree of proteinuria in patients with DG can predict the presence of CG and/or is associated with severity of DG.

Design: A retrospective review was performed on 206 renal biopsies with diagnosis of DG. CG was found in 11 of 206 renal biopsies. The 24-hour urine protein excretion (UPE) rate was available in all 11 patients with CG and in 76 patients without CG. The renal biopsies were examined by light, immunofluorescence, and electron microscopy.

Results: CG was found in 11 (5.3%) patients. The CG diagnoses were as follows: membranous glomerulonephritis (5 cases), immunoglobulin (Ig) A nephropathy (2 cases), postinfectious glomerulonephritis (GN) (1 case), type I membranoproliferative glomerulonephritis (1 case), anti-neutrophil cytoplasmic antibody-associated GN (1 case), and anti-glomerular basement membrane disease (1 case). The 24-hour UPE rate had a mean of 9.7 g (range, 5.5-14 g) in the 11 patients with CG and 8.3 g (range, 1.5-24 g) in the 76 patients without CG. Among the 76 patients without CG, 25 (33%) had more than 10 g UPE per 24 hours. There is no correlation between severity of glomerulopathy and degree of proteinuria in patients without CG.

Conclusions: Although patients with CG had severe proteinuria, the high level of UPE by itself does not predict the presence of CG. The factor( s) responsible for the marked difference of UPE in diabetic patients without CG is (are) currently under investigation.

Immunohistochemical Differentiation of Low-Grade Serous Carcinoma With Micropapillary Histology From Other Tumors With Micropapillary Histologic Features

(Poster No. 10)

Harsha S. Desai, MD (harsha.desai@beaumont.edu); Mitual B. Amin, MD. Department of Anatomic Pathology, William Beaumont Hospital, Royal Oak, Mich.

Context: Micropapillary histology of tumors is being increasingly recognized, with reported occurrences in many organs. This knowledge is useful when observing micropapillary features in metastatic carcinomas (CAs) from an unknown primary. Our aim is to study a panel of immunohistochemical stains that would help in the differential diagnosis of tumors with micropapillary histology.

Design: Fifty primary tumors from urinary bladder (n = 14), breast (n = 12), lung (n = 12), pancreas (n = 6), and ovary (n = 6), and 9 cases of metastatic CA with micropapillary pattern, were included. The immunohistochemical panel included cytokeratin (CK) 7, CK17, CK20, thyroid transcription factor 1 (TTF-1), WT-1, p63, and estrogen receptor (ER).

Results: All ovarian serous CAs were positive for WT-1, and 67% were also positive for ER. All cases of transitional cell carcinoma (TCC) were positive for CK20, and 80% also showed focal positivity with p63. TTF-1 was positive in all lung CAs. Eighty percent of breast CAs were positive for ER. CK17 was focally positive in all ovarian serous CAs and pancreatic CAs and in 80% of TCCs. CK20 was positive in 60% of pancreatic CAs and 20% of breast CAs. In metastatic tumors, the panel was accurate in confirming the site of origin in all 7 cases.

Conclusions: Micropapillary histology is a distinctive feature of which recognition can help in the identification of the site of primary. The staining patterns in all these different tumors showing micropapillary histology is quite distinctive (serous CA [WT1^sup +^, ER^sup +^, CK17 focally^sup +^], TCC [CK20^sup +^ and p63 focal^sup +^], breast CA [ER^sup +^, WT1^sup -^], lung CA [TTF-1^sup +^], and pancreas CA [CK17 focally^sup +^, CK20^sup +^, ER^sup -^, WT1^sup -^, TTF-1^sup -^, p63^sup -^]).

Thrombotic Microangiopathy in Cocaine Abuse: Case Report With Review of the Literature

(Poster No. 11)

Harsha S. Desai, MD1 (harsha.desai@beaumont.edu); Jeffrey Gold, MD2; Alma R. Reyes, MD1; Chung-ho Chang, MD.1 Departments of 1Anatomic Pathology and 2Nephrology, William Beaumont Hospital, Royal Oak, Mich.

Cocaine use is the most frequent cause of drug-related death in the United States. The association of cocaine use and myocardial ischemia/infarction is well known and its association with acute renal failure is less well recognized. Only 4 cases of cocaine-induced thrombotic microangiopathy have been reported. We report a case of cocaine abuse associated with biopsy proven thrombotic microangiopathy in a 29-year-old man. Laboratory values on admission included blood urea nitrogen, 68; creatinine, 7.1 mg/dL; platelets, 41 103/µL; 6 to 10 schistocytes per highpower field in blood smear; lactate dehydrogenase, 4000 U/L; haptoglobin, 13 mg/dL; and creatine kinase, 886 U/L. Histopathology revealed focal cortical ischemic necrosis with marked congestion of glomerular capillaries, and active tubular degeneration with red cell casts; prominent ischemic collapse of glomeruli in other areas; rare pigmentary deposits in tubules positive for myoglobin stain; and concentric myointimal proliferation (onion-skinning) of small arteries. Immunofluorescence demonstrated 1+ granular staining for fibrinogen along the glomerular capillary walls in 1 glomerulus. Electron microscopy revealed distended glomerular capillaries with partly degenerated and fragmented red cells mixed with cellular debris. Focal disruptions of cell membranes of the lining endothelial cells with fragments of red cells, degenerated thrombocytes, and occasional fibrin tactoids were seen within widened subendothelial spaces. Renal tubules showed active degenerative changes with scattered calcium deposits within the cytoplasm. One medium-sized artery showed fibrin thrombosis. In conclusion, renal biopsy showed glomerular and vascular changes characteristic for thrombotic microangiopathy with concomitant acute tubular necrosis and residual evidence of recent rhabdomyolysis. Electron microscopic findings support vascular endothelial damage being a major cause of renal pathology.

Epithelioid Leiomyoma of the Kidney: Case Report and Discussion of Differential Diagnosis

(Poster No. 12)

Tarek Hammour, MD (thammou1@hfhs.org); Min Woo Lee, MD. Department of Pathology and Laboratory Medicine, Henry Ford Hospital, Detroit, Mich.

Renal leiomyomas are extraordinarily rare neoplasms that usually occur in adults as incidental findings. We report a case of an epithelioid variant of renal leiomyoma and discuss its differential diagnosis. A 45-year-old woman had chest computed tomography scan for pneumonia. A left renal mass was identified. The partial nephrectomy specimen showed a 4.8-cm, well-circumscribed, grey-tan mass with solid and homogenous cut surface. No hemorrhage or necrosis was present. Microscopically, the mass was composed of nests of epithelioid polygonal cells separated by thick hyaline cords. Prominent thick-walled blood vessels were noted with adjacent tumor cells radiating from the perivascular spaces. No adipocytes were seen. Tumor cells showed mild cytologic atypia and had moderate eosinophilic cytoplasm with frequent cytoplasmic clearing and round to oval central nuclei with vesicular chromatin (Figure 22). Rare mitotic activity was noted (<1 per 10 high-power fields). Tumor cellswere positive for HHF-35 and desmin. Negative stains included periodic acid-Schiff, HMB-45, Melan-A, c-kit, CD31, and CD34. Ultrastructurally, no rhomboid-shaped renin granules were seen. Leiomyomas arising fromthe kidney are rare neoplasms that do not differ pathologically from leiomyomas elsewhere. They usually originate in the renal capsule or cortex. Epithelioid leiomyomas may be difficult to differentiate from the more common epithelioid angiomyolipoma; the latter is invariably HMB-45 positive. The differential diagnosis also includes juxtaglomerular cell tumor, which is usually immunoreactive for CD34 and ultrastructurally shows the characteristic rhomboid-shaped renin granules. The recently described renal glomus tumor can be differentiated by more frequent involvement in the renal pelvis, delicate small vessels, and desmin negativity.

Diagnostic Utility of P504S/p63 Cocktail, Prostate-Specific Antigen, and Prostatic Acid Phosphatase in Verifying Prostate Carcinoma Involvement in Seminal Vesicles: A Study of 57 Cases of Radical Prostatectomy Specimens of Pathologic Stage pT3b

(Poster No. 13)

Aaron M. Harvey, MD (amharvey@tmhs.org); Beverly Grice, HTL; Alberto Ayala, MD; Qihui Zhai, MD. Department of Pathology, The Methodist Hospital, Houston, Tex.

Context: Seminal vesicle invasion by prostate carcinoma is directly associated with tumor staging, and verification is challenging when the tumor demonstrates cribriform and/or papillary growth patterns or the foci of interest is small. P504S is overexpressed in prostate carcinoma and high-grade intraepithelial neoplasia with cytoplasmic immunoreactivity, while p63 stains basal cell nuclei of benign prostate glands. The combination of these antibodies using different colors is widely used. We aim to evaluate the usefulness of a 1-color P504S/p63 cocktail immunostain to verify prostate carcinoma within seminal vesicle.

Design: Fifty-seven radical prostatectomy specimens (pT3b) were retrieved. Sections of formalin-fixed, paraffin-embedded blocks containing seminal vesicle with prostate carcinoma involvement were immunostained using primary antibodies against P504S/p63, prostate-specific antigen (PSA), and prostatic acid phosphatase (PAP) and were detected with the Dako polymer system (Dako, Carpinteria, Calif).

Results: Prostate carcinoma cells from all 57 (100%) cases were diffusely positive for P504S, PSA, and PAP with cytoplasmic staining and with no p63 nuclear staining (0%). In all 57 case, the seminal vesicle epithelium was negative (with occasional positively staining cells) (0%) for all 3 markers with distinct p63 nuclear staining of the basal cells (100%). Benign prostate tissue was positive for PSA and PAP. The proteinaceous material in seminal vesicle lumens was prone to unspecific stains, with PSA more obvious than P504S and PAP.

Conclusions: The P504S/p63 1-color cocktail is practical and cost-effective. It is superior to PSA or PAP when the sections contain both seminal vesicle and benign glands, because PSA and PAP cannot distinguish benign from malignant glands.

A Limited Immunohistochemical Panel Helps Distinguish Granular Type of Conventional Renal Cell Carcinoma From Other Nonpapillary Renal Oncocytic Neoplasms

(Poster No. 14)

Loren P. Herrera, MD1; Carmen Gomez-Fernandez, MD2; Isildinha Reis, DPH3; Kara Hamilton, PhD3; Merce Jorda, MD2 (mjorda@med.miami.edu). 1Department of Pathology, University of Miami/Jackson Memorial Hospital, Miami, Fla; 2Department of Pathology, University of Miami Miller School of Medicine/Jackson Memorial Hospital and The University of Miami Sylvester Comprehensive Cancer Center, Miami, Fla; 3Department of Epidemiology and Public Health, University of Miami Miller School of Medicine/The University of Miami Sylvester Comprehensive Cancer Center, Miami, Fla.

Context: Nonpapillary renal neoplasms with granular morphology may represent different types of renal tumors, such as conventional carcinoma (CC), chromophobe carcinoma, and oncocytoma. Their distinction may be challenging, particularly in small biopsy samples. The aim of this study is to identify a limited immunohistochemical panel that may help discriminate granular cell CC from its morphologic mimics.

Design: We selected 44 nonpapillary renal neoplasms with granular morphology, 19 CCs, and 25 non-CCs (18 chromophobe carcinomas and 7 oncocytomas) obtained by partial or radical nephrectomy performed at Jackson Memorial Hospital. CD10, E-cadherin, N-cadherin, kidney-specific (Ksp)-cadherin, recepteur d'origine Nantais (RON), cytokeratin (CK) 7, and c-kit immunohistochemistry was performed in all cases.

Results: Difference in the immunoreactivity pattern between CCs and chromophobe carcinomas/oncocytomas was statistically significant (P = .03) for CD10, E-cadherin, N-cadherin, CK7, and c-kit. When limited to diffuse staining of most tumor cells, positivity for CD10 and N-cadherin and negativity for c-kit was specific for CC (P = .01). Only 1 chromophobe carcinoma showed this immunohistochemical profile, whereas none of the oncocytomas were immunoreactive for these antibodies.

Conclusions: A limited immunohistochemical panel that includes CD10, N-cadherin, and c-kit is helpful in the distinction of granular CC from other nonpapillary oncocytic renal neoplasms. The diffuse pattern of expression of CD10 and N-cadherin is an advantageous feature for core biopsy samples of renal tumors.

Multilocular Cystic Renal Cell Carcinomas Have an Association With Metabolic Syndrome

(Poster No. 15)

Vera Tesic, MD1 (ssetty@uic.edu); Kristopher McGee, MD1; Jenny Lee, MD2; Swati Mehrotra, MD1; Suman Setty, MD, PhD.1 Departments of 1Pathology and 2Medicine, University of Illinois at Chicago.

Context: Multilocular cystic renal cell carcinoma (MCRCC) and cystic renal cell carcinoma (CRCC) are low-grade and low-stage carcinomas; therefore, they are good candidates for nephron-sparing surgery. Diabetes and components of metabolic syndrome (eg, obesity) are established risk factors for renal cell carcinoma. Our premise was that a predilection for secondary native renal disease (eg, diabetes) would be high in individuals with MCRCC and CRCC. This would make nephron-sparing surgery even more necessary.

Design: We searched our surgical pathology files for cases of organconfined MCRCC and CRCC. The presence of metabolic syndrome was defined by the criteria accepted by the American Heart Association and the National Heart, Lung, and Blood Institute based on the presence of 3 or more of the following criteria: increased body mass index, elevated triglycerides, reduced high-density lipoprotein, hypertension, and fasting glucose. Diabetes was diagnosed using standard criteria.

Results: Six cases were found (Table). All 6 adults, including 3 with MCRCC and 3 with CRCC, were hypertensive; 3 of 6 had diabetes with varying degrees of diabetic nephropathy in the nonneoplastic kidney, and 1 of 6 had lupus nephritis. A 2-tailed P value of less than .001 was obtained when the incidence of metabolic syndrome/diabetes in MCRCC/CRCC was compared with the general population.

Conclusions: There is a significant association between metabolic syndrome/diabetes and MCRCC/CRCC. These individuals are good candidates for nephron-sparing surgery whenever surgically feasible.

Pure Glandular Endometrioid-like Yolk Sac Tumor of the Testis

(Poster No. 16)

Marc A. Harrison, MD1 (Marc-Harrison@ouhsc.edu); Sreenivas Vemulapalli, MD2; James Seay, MD3; Liang Cheng, MD4; Thomas M. Ulbright, MD4; Barbara Bane, MD.1 Departments of 1Pathology and 2Urology, Oklahoma University Health Sciences Center, Oklahoma City; 3Department of Pathology, Norman Regional Health System, Norman, Okla; 4Department of Pathology, Indiana University Medical Center, Indianapolis.

Yolk sac tumors (YSTs) of the testis composed of a predominantly or purely glandular pattern are exceedingly rare and may present diagnostic difficulty due to deceptive histology simulating endometrioid adenocarcinoma. Immunohistochemical and fluorescence in situ hybridization (FISH) studies may be helpful in establishing the diagnosis. We present the pathologic, immunohistochemical, and FISH findings of a glandular YST of the testis in a 61-year-old man. An 8-cm tumor with cystic degeneration was removed at radical orchiectomy. Histologically, the tumor showed a complex glandular pattern with focally prominent subnuclear and supranuclear glycogen vacuoles resembling secretory endometrioid carcinoma (endometrioid-like YST; Figure 23). Prominent basement membrane deposits were noted throughout the tumor. Intratubular germ cell neoplasia was not identified. Immunohistochemical studies showed focal positivity for AFP (Cell Marque, Hot Springs, Ark) and PLAP (Cell Marque) and mostly negative staining for epithelial membrane antigen (Cell Marque), supporting the diagnosis of glandular (endometrioid-like) YST. The tumor was limited to the testis without invasion of the tunica albuginea or spermatic cord; no vascular-lymphatic invasion was seen (pT1 NX MX). Subsequent retroperitoneal lymphadenectomy demonstrated metastatic mature teratoma. FISH studies performed on formalin-fixed, paraffin-embedded tissue from the testicular and retroperitoneal tumors showed isochromosome of the short arm of chromosome 12 [i(12p)], the hallmark genetic marker of testicular germ cell tumors. Purely glandular patterns of YST are typically seen in metastases resected after chemotherapy rather than in primary testicular germ cell tumors. Recognition of primary YST occurring in predominantly or purely glandular form in the adult testis is essential to avoid misdiagnosis and ensure appropriate therapy.

Fusion of ETS Family Members With Distinct 5+ Partners Typify a Unique Set of Gene Rearrangements in Prostate Cancer

(Poster No. 17)

Rohit Mehra, MD (mrohit@med.umich.edu); Bo Han, MD; Scott A. Tomlins, PhD; Nallasivam Palanisamy, PhD; Rajal B. Shah, MD; Arul M. Chinnaiyan, MD, PhD. Department of Pathology, University of Michigan, Ann Arbor.

Context: Deciphering the gene fusions that characterize prostate cancer will lead to the identification of molecular aberrations implicated in the biology, treatment, and outcome of this disease. In the context of our recent discovery of ETS gene rearrangements in prostate cancer, we sought to investigate known and novel ETS aberrations across prostate cancer progression.

Design: Using a previously validated fluorescence in situ hybridization split probe strategy, we interrogated tissue microarrays with benign and prostate cancer cases (158 localized and 30 advanced cancers) for aberrations involving TMPRSS2, ERG, ETV1, ETV4 genes, and other 5' fusion partners.

Results: We found TMPRSS2/ERG fusion to be the most common molecular subtype in prostate cancer with TMPRSS2 and ERG rearrangement present in 55% and 48% of American males with localized prostate cancer, respectively (Figure 24, A and B: Colocalized yellow signals in prostate cancer cells lacking TMPRSS2 and ERG rearrangement, respectively; C and D: TMPRSS2 and ERG rearrangement-positive cases showing split apart [red and green] signals). ETV1 and ETV4 aberrations were present in 4% of cases. Other molecular subtypes present in a smaller percentage of cases included SLC45A3 (4.5%), HNRP2AB1 (1.0%), and C15ORF21 (1.1%). Benign prostate or prostate atrophy tissues did not show any fusions. Forty-eight percent, 37%, 11%, and 4% of metastatic hormone refractory prostate cancer cases showed TMPRSS2, ERG, ETV1, and ETV4 aberrations, respectively.

Conclusions: We discovered novel ETS fusions and validated the high percentage of these aberrations in prostate cancer. Identification of distinct gene fusions provides unique potential targets with implications in the treatment of prostate cancer.

Financial Disclosures: The University of Michigan has filed a patent on ETS gene rearrangements in prostate cancer, on which Dr Rohit Mehra, Dr Scott A. Tomlins, and Dr Arul M. Chinnaiyan are coinventors, and the diagnostic field of use has been licensed to Gen-Probe Incorporated. Gen-Probe has not played a role in the design and conduct of the study; or in the collection, analysis, or interpretation of the data; or in the preparation, review, or approval of the manuscript.

BCL-2, Ki-67, and p16Ink4 Expression in Glandular Embryonal Remnants in Hernia Sacs

(Poster No. 18)

Daniel G. Rosen, MD (dgrosen@bcm.edu); Rodolfo Laucirica, MD; Edwina J. Popek, MD. Department of Pathology, Baylor College of Medicine, Houston, Tex.

Context: Glandular inclusions in inguinal hernia sacs are an infrequent finding. It has been postulated that they may represent vestiges of the Müllerian or Wolffian ducts that failed regression during development. However, it is unclear which factors may contribute to its persistence.We investigated the expression of the antiapoptosis marker BCL-2, the proliferation index by Ki-67, and the senescence-associated maker p16Ink4 in glandular embryonal remnants.

Design: Electronic records from the Texas Children's Hospital from 2000 to 2008 were searched for herniorrhaphy specimens showing glandular embryonal remnants. A tissue microarray block was constructed with 9 random embryonal remnant cases, 5 normal epididymis, and 3 normal testes obtained from autopsy specimens. Immunoperoxidase staining for BCL-2, Ki-67, and p16Ink4 were semiquantitatively scored.

Results: A total of 6086 herniorrhaphy specimens corresponding to 5352 boys (88%) and 734 girls (12%) were found. Tubular embryonal remnants were present in 109 cases (1.8%), all of which were male patients. The age range was from 10 weeks to 17 years old. Expression of BCL-2 was similar in embryonal remnants compared with epididymis but negative in all 3 normal seminiferous tubules. Ki-67 labeling index was less than 5% in all tissues. p16Ink4 expression was weakly and patchy positive only in 2 cases of normal seminiferous tubules (Table).

Conclusions: BCL-2 expression is similar in embryonal remnants and normal epididymis but higher compared with normal testis. Embryonal remnants do not show an increase in proliferation index and lack senescence marker. Lack of apoptosis might be a contributing factor for the persistence of embryonal remnants.

Utility of Renal Cell Carcinoma Marker, α-Methylacyl-CoA Racemase, PAX-2, and WT-1 in the Differential Diagnosis of Metanephric Adenoma Versus Type 1 Papillary Renal Cell Carcinoma

(Poster No. 19)

Byron Moore, MD1 (bhmoore2@tmhs.org); Jane Dancer, MD1; Pheroze Tamboli, MD2; Youngmi Cho, MD3; Jim Zhai, MD1; Jae Y. Ro, MD, PhD1; Alberto Ayala, MD1; Steven Shen, MD, PhD.1 1Department of Pathology, The Methodist Hospital, Houston, Tex; 2Department of Pathology, University of Texas M. D. Anderson Cancer Center, Houston, Tex; 3Department of Pathology, Asan Medical Center, Seoul, Republic of Korea.

Context: Metanephric adenoma (MA) is a benign renal neoplasm that shares many overlapping morphologic features with low-grade type 1 papillary renal cell carcinoma (PRCC). The aim of this study was to compare and explore the utility of emerging immunohistochemical markers, including -methylacyl-CoA racemase (AMACR) and PAX-2, in the differential diagnosis.

Design: Eight cases of MA and 11 cases of low-grade type 1 PRCC were retrieved from the pathology files at The Methodist Hospital, M. D. Anderson Cancer Center, and Asan Medical Center in Korea. Five histologic features (papillary growth, glomeruloid, solid growth pattern, presence of psammoma bodies, and macrophages) were evaluated, and immunohistochemical staining of AMACR and PAX-2, in addition to RCC marker (RCCM) and WT-1, were performed on the routine formalin-fixed, paraffin-embedded specimens.

Results: Six of 8 MAs and 11 of 11 PRCCs showed a papillary pattern; 4 of 8 MAs and 4 of 11 PRCCs showed glomeruloid pattern; 8 of 8 MAs and 7 of 11 PRCCs showed solid pattern; 6 of 8 MAs and 1 of 11 PRCCs showed psammoma bodies; and 1 of 8 MAs and 7 of 11 PRCCs showed macrophages (Table).

Conclusions: MAs and some type 1 PRCCs shared many similar histologic features. A panel of immunohistochemical stains with RCCM, AMACR, and WT-1 can be a very useful adjunct to the differential diagnosis of MA (RCCM^sup -^/AMACR^sup -^/WT1^sup +^) versus type 1 PRCC (RCCM^sup +^/AMACR^sup +^/WT1^sup -^).

Intraosseous Hibernoma of the Femur: An Unusual Case With a Review of the Literature

(Poster No. 20)

Alma R. Reyes, MD1 (alma.reyes@beaumont.edu); Ronald B. Irwin, MD2; Jon D. Wilson, MD1; Harsha S. Desai, MD.1 1Department of Anatomic Pathology, William Beaumont Hospital, Royal Oak, Mich; 2Department of Orthopedic Surgery/Oncology, Mount Clemens RegionalMedical Center, Mount Clemens, Mich.

First described by Friedrich Merkel, a German anatomist, in 1906, hibernomas are rare benign tumors consisting of brown fat and are considered a special form of fetal adipose tissue. Although tumors arising from white adipose tissue are among the most common soft tissue lesions, hibernomas are among the rarest, with fewer than 200 cases reported in the literature. Brown adipose tissue has been postulated to play a role in thermoregulatory functions of hibernating animals and newborn humans. The brown color is due to the rich vascularity and high cytochrome content of the metabolic, active, brown fat cells. In adults, these cells are usually found in regions where remnants of fetal adipose tissue remain, such as muscle and subcutaneous tissue. Hibernomas are slow-growing, painless tumors for which total excision is advocated. The rarity and unusual histologic features of hibernomas can make the diagnosis difficult. We report an unusual case of an intraosseous hibernoma with bilateral femur involvement in a 54-year-old man. Although conventional lipomas have on occasion been reported in intraosseous locations, to our knowledge, hibernomas have not. We discuss the clinical, radiographic, and pathologic findings of an intraosseous hibernoma in this patient and review the prior literature.

PEComa of the Bone: Case Report and Algorithmic Approach to Clear Cell Tumors of the Bone

(Poster No. 21)

Ihsane Ouansafi, MD1 (iouansaf@nshs.edu); Silvat Sheikh-Fayyaz,MD1; Samuel Kenan, MD2; Leonard B. Kahn, MD.1 Departments of 1Pathology and 2Orthopedic Surgery, Long Island Jewish Medical Center, New Hyde Park, NY.

PEComas are defined as mesenchymal tumors composed of histologically and immunohistochemically distinctive perivascular epithelioid cells. PEComas of the bone are extremely rare. We report a case of PEComa in the fibula. The patient is a 93-year-old woman who presented with right extremity pain. An x-ray showed a pathologic fracture of the right distal fibula with an adjacent radiolucent lytic lesion. A biopsy of the lesion was performed and the patient refused to undergo surgical resection at the time. A metastatic workup did not show evidence of a primary tumor elsewhere. A radiologic follow-up showed a progressive enlargement of the lesion, and a total surgical excision was subsequently performed. The tumor consisted of nests of clear to eosinophilic polygonal epithelioid cells separated by thin-walled vessels. Mild atypia was present. No mitotic activity was noted. The differential diagnosis included metastatic clear cell carcinoma, clear cell sarcoma, alveolar soft part sarcoma, clear cell chondrosarcoma, and PEComa. The tumor was positive for HMB-45 and transcription factor E3. It was negative for S100, Melan-A, microphthalmia-associated transcription factor, actin, desmin, calponin, CD1a, vimentin, CD10, and cytokeratin. No granules were identified on periodic acid-Schiff diastase stain. Electron microscopy showed the presence of premelanosomes. A diagnosis of PEComa was rendered based on these ancillary studies. PEComas arise exceptionally in the bone and could be easily misdiagnosed. We propose a comprehensive approach to the differential diagnosis of clear cell tumors in the bone by an algorithmic approach with the usage of the most updated immunohistochemical and molecular tools.

Pleomorphic Liposarcoma Presenting as an Exophytic Polypoid Mass in the Second Toe of a Young Adult Female

(Poster No. 22)

Syed S. Ahmed, MD (taahas@yahoo.com); Majd Jundi, MD. Department of Pathology, Al-Hada and Taif Military Hospital, Taif, Saudi Arabia.

Pleomorphic liposarcoma represents a rare subtype of liposarcoma, accounting for approximately 5% of all liposarcomas and 20% of all pleomorphic sarcomas. This subtype is a pleomorphic, high-grade sarcoma containing a variable number of pleomorphic lipoblasts. Most pleomorphic liposarcomas are in the deep soft tissue of the extremities (lower greater than the upper limbs) in elderly patients with equal sex distribution. Examples in the subcutis or purely dermal pleomorphic liposarcoma have been reported. We are unaware of pleomorphic liposarcoma presenting as an exophytic polypoid mass in the toe of a young patient. A 23-year-old woman presented with a rapidly growing polypoid mass on the medial aspect of the second right toe. The excised surgical specimen consisted of a 2.4-cm polypoid mass covered with skin. No surface ulceration was present. The cut surface was yellow-white with no necrosis or myxoid changes. The histologic examination revealed a high-grade tumor with a vague lobular pattern and marked cellular atypia. The tumor cells were predominantly clustered around the vascular spaces and contained many tumor giant cells. The degree of cellular atypia was far in excess of the pleomorphic lipoma as described in the literature. Immunostains were negative for S100 protein, Melan-A, desmin, and actin.With the proliferation marker Ki-67, 20% positivity was present. Fluorescence in situ hybridization analysis with Vysis LSI CHOP Dual Color, Break Apart Rearrangement Probe for cytogenetic location 12q13 (Abbott Molecular, Abbott Laboratories, Des Plaines, Ill) showed 5% of the cells with translocation and 95% of the cells with normal pattern.

Comparison of Cytogenetic, Nuclear Morphometric, and Ultrastructural Features of Giant Cell Tumors of Bone and Soft Tissue

(Poster No. 23)

Matthew P. Walters, MD (mpwalter@mcw.edu); Vladimir Osipov, MD. Department of Pathology, Medical College of Wisconsin, Milwaukee.

Context: Giant cell tumors of bone (GCTB) and soft tissue (GCTST) are neoplasms with similar morphology and behavior. Pleomorphism varies between the mononuclear component of the GCTB and GCTST. Cytogenetically, GCTB shows frequent telomeric association and GCTST shows complex alterations. Ultrastructural features of GCTST were unstudied in the past.

Design: Ten cases of GCTB with known karyotype were studied. Ten cases of GCTST were also studied, one of which was karyotyped. Cases were screened by several pathologists to rule out giant cell rich sarcomas. Cases were examined at 400 magnification to measure nuclear sizes of 100 mononuclear cells from each case using a micrometer. Data was analyzed using Wilcoxon signed rank test. Electron microscopy was performed on 2 cases of each tumor type.

Results: Karyotypes of GCTB showed telomeric association in 7 of 10 cases. GCTST karyotype demonstrated large, structural abnormalities with modal numbers of 44 to 45 chromosomes; 2 of 20 cells were tetraploid. Statistical analysis showed significant nuclear morphometric differences between GCTB and GCTST (P < .001). Data showed no difference between the tumors within each group (range, P = .25-.76). Ultrastructural analysis of GCTB and GCTST shows complementary morphology.

Conclusions: Our study suggests that GCTB and GCTST have different genetic anomalies. GCTB and GCTST have statistically significant pleomorphic differences in their mononuclear cells; likely due to a greater number of variable chromosomal abnormalities within GCTST. This combined with a higher documented rate of metastases than that seen in GCTB supports a classification of GCTST as a tumor of low malignant potential.

A Rare Case of Atypical Lipomatous Tumor of the Stomach

(Poster No. 24)

Sarah K. Galfione, MD (skgalfione@tmhs.org); Jose Gonzalez-Berjon, MD; Alberto Ayala, MD. Department of Pathology, The Methodist Hospital, Houston, Tex.

Atypical lipomatous tumors (also known as well-differentiated liposarcoma) are the most common soft tissue sarcomas, but they have very rarely been described in the stomach. This report concerns a 63-year-old woman with a history of nausea, left upper quadrant pain in the abdomen after meals, vomiting, early satiety, and a loss of 80 pounds in the last 2 to 3 years. The tumor was located in the fundus and was 4 cm distal to the gastric esophageal junction; it was also submucosal, with no mucosal involvement. A local resection showed a 5.5-cm well-circumscribed mass with a homogenous, soft yellow-tan, glistening appearance and with a shiny tan-pink mucosal surface. Microscopically, the mass was limited to the submucosa and was composed of adipocytes that showed variation in size and shape with scattered atypical enlarged hyperchromatic cells and occasional floret cells. There was an increase in fibrous stroma with scattered atypical cells. Mitotic activity was rare. The findings were diagnostic of an atypical lipomatous tumor of the stomach. Review of the literature shows 10 previously reported cases of this entity during a 6-decade period. The age at presentation ranged from 15 to 86 years, and the lesions were more common in men than in women. Nausea and vomiting were common symptoms. All patients followed a benign course without recurrence, dedifferentiation, or metastasis.

Blue Rubber Bleb Nevus Syndrome: Lymphangiomatosis-like Growth Pattern Within the Uterus and Immunohistochemical Analysis

(Poster No. 25)

Rajal C. Patel, BS; Debra L. Zynger, MD (d-zynger@md.northwestern.edu); William B. Laskin, MD. Department of Pathology, Northwestern University, Chicago, Ill.

Blue rubber bleb nevus syndrome (BRBNS) is a rare, primarily sporadic condition that is characterized by vascular lesions that principally involve the skin and gastrointestinal tract. Although considered a venous malformation, telangiectatic capillaries and arteriovenous malformations have also been reported in BRBNS. Herein, we expand the morphologic spectrum and the immunohistochemical profile of vascular lesions in this disorder by analyzing a case of BRBNS with a lymphangiomatosis-like vascular proliferation within the uterus, a site heretofore rarely reportedly involved in BRBNS. A 28-year-old woman with documented viscerocutaneous BRBNS underwent surgical excision of a 23-cm mass that involved the peritoneal cavity and uterus. Lesional vessels with features of venous malformation were identified in the pelvis and ureter. A labyrinth of variably sized vascular spaces lined only by an attenuated layer of cytologically bland endothelial cells was observed dissecting uterine tissues and sequestering remnants of myometrium. Immunohistochemical results from myometrial tissue included strong, diffuse expression of CD31; variable expression of CD34; strong but patchy expression of D2-40; and weak, patchy expression of factor-VIII-related antigen within lesional endothelial cells. Patchy linear subendothelial expression of collagen type IV was identified. Ki-67 expression was noted in approximately 1% of cells. GLUT-1 and WT-1 were not expressed. The morphologic spectrum of vascular lesions in BRBNS includes lymphangiomatosis-like permeative growth of thin-walled vascular structures that show immunohistochemical evidence of vascular and lymphatic differentiation. Immunohistochemical absence of GLUT-1 and WT-1 and negligible Ki-67 expression support the currently accepted belief that the vascular lesions in BRBNS are malformations.

A Rare Case of Segmental Neurofibromatosis Involving the Sciatic Nerve

(Poster No. 26)

Aron M. Trocchia, MD1; Kimberly Les, MD1; Jon D. Wilson, MD2; Alma R. Reyes, MD2 (alma.reyes@beaumont.edu). Departments of 1Orthopedic Surgery and 2Anatomic Pathology, William Beaumont Hospital, Royal Oak, Mich.

The deforming lesions of neurofibromatosis (NF) have been described throughout literature for centuries. In 1856, Virchow depicted NF-1 with its cutaneous manifestations and elephantiasis neuromatosa in his work "Krankhafte Geschwülste." Throughout the course of the 20th century, 8 forms of NF have been delineated. NF-5, or segmental NF, was first described by Crowe and colleagues in 1956 and was later defined by Ricarrdi. The incidence of NF-5 is far more rare than the 1 in 3000 people affected by NF-1. Segmental NF is an extremely rare variant of NF involving a single extremity without pathologic features crossing beyond the midline. Although there have been many reports of segmental NF, only rare cases involve the extremities. To our knowledge, there is only one report of segmental NF with involvement of the sciatic nerve. We report a case of segmental NF with several dozen intraneural neurofibromas within the sciatic nerve and its branches from the gluteal fold to the level of the proximal tibia. Clinical, histologic, and genetic findings are discussed along with a brief review of the literature involving segmental NF.

Utility of CD10 and Cytokeratin 7 Expression as Diagnostic Markers in Epithelioid Hemangioendothelioma

(Poster No. 27)

Maria McIntire, MD (Maria≥McIntire@rush.edu); Vijaya Reddy, MD; Paolo Gattuso, MD. Department of Pathology, Rush University Medical Center, Chicago, Ill.

Context: Epithelioid hemangioendothelioma (EHE), a rare vascular endothelial tumor, can occur in several organs, including liver, lung, bone, and head and neck, where it may mimic metastatic carcinoma. Immunohistochemical studies are often needed to make the correct diagnosis. Most EHEs are positive for endothelial markers CD31, CD34, factor VIII, and recently podoplanin, but the expression of these markers can be variable. We studied the expression of CD10 and cytokeratin 7 (CK7) in EHE from various sites to assess the utility of these markers in diagnosing EHE.

Design: From 1997 to 2008, 9 patients (5 men, 4 women; age range, 23-60 years; mean age, 44 years) were diagnosed with EHE at these sites: 4 bone, 2 liver, 2 head and neck, and 1 lung. Tumors were stained for CD10, CK7, and at least one vascular marker.

Results: All tumors were positive for CD31. Three of 5 extraosseous EHEs expressed CD10 and CK7 (2 liver, 1 head and neck). All cases of primary bone EHE were negative for CD10 and CK7.

Conclusions: Immunohistochemical evidence of endothelial differentiation is an important criterion for the diagnosis of EHE. Cytokeratin positivity has often been used to differentiate between EHE and carcinoma. However, our study shows that 60% of extraosseous EHEs express CK7. Additionally, 60% were positive for CD10. Although the epithelioid morphology and the coexpression of CD10 and CK7 in EHE may lead to a mistaken diagnosis of metastatic carcinoma, inclusion of a vascular marker in the panel may improve the diagnostic accuracy of extraosseous EHE.

Adenocarcinoma Arising in a Mature Sacrococcygeal Teratoma in a 58-Year-Old Woman

(Poster No. 28)

Mary Pietrangelo, MD (Mary.Pietrangelo@beaumont.edu); Jacqueline Trupiano, MD. Department of Anatomic Pathology, William Beaumont Hospital, Royal Oak, Mich.

Although common in infants, sacrococcygeal teratomas (SCTs) are distinctly uncommon in adults, with only 92 cases reported in the literature. In contrast to the externally visible lesions of infancy, SCTs in adults typically present as large intrapelvic masses. Tumors presenting in adulthood have an increased risk of malignancy due to either a malignant germ cell component (malignant SCT) or malignant transformation of mature elements (SCT with malignant transformation). Only 20 malignant cases of SCT in adults have been reported in the literature to date. We report on a 58-year-old woman with a 9.6 6.4-cm cystic mass anterior to the sacrum, which was detected incidentally as extrarectal fullness during a routine colonoscopy. The specimen was entirely submitted in 45 blocks. Microscopy revealed components of a mature cystic teratoma with small foci of poorly differentiated adenocarcinoma present in only 5 slides. The adenocarcinoma showed patchy immunoreactivity for cytokeratins 7 and 20, CDX-2, and CA 125. The cells were negative for estrogen receptors, WT-1, surfactant-A, and thyroid transcription factor 1. Although uncommon, SCT should be considered in the differential diagnosis of pelvic/retroperitoneal masses in adults. These tumors must be sampled extensively because the risk of a malignant germ cell component or malignant transformation increases with age and has a profound impact on ultimate treatment and prognosis.

Unique Coexpression of S100 Protein and Calretinin in Thoracic Chordoma

(Poster No. 29)

Uyen Ly, DO1 (debly806@hotmail.com); Santhi Ganesan, MD1; Thomas Temes, MD2; Joseph F. Tomashefski, MD.1 Departments of 1Pathology and 2Surgery, MetroHealth Medical Center, Case Western Reserve University, Cleveland, Ohio.

Chordomas arise from embryonic notochord, constitute less than 5% of primary malignant bone tumors, and have a propensity for local invasion and recurrence. We present a 60-year-old woman with left-sided chest pain and dyspnea. Chest computed tomography revealed a posterior mediastinal, retropleural, paraspinous mass without evidence of bone invasion. The initial core biopsy was interpreted as a low-grade epithelioid neoplasm, which was immunoreactive for cytokeratin, epithelial membrane antigen, S100 protein, calretinin, and vimentin. The differential diagnosis included chordoma versus a low-grade mesothelial neoplasm. The subsequent resection specimen demonstrated characteristic physaliphorous cells in a chondromyxoid and hyaline matrix with immunohistochemical features similar to those of the core biopsy specimen (Figure 25). Ultrastructurally, the cells exhibited abundant cytoplasmic vacuoles and stubby microvilli. Cytogenetic analysis revealed trisomy 7. The final diagnosis was chondroid chordoma of the thoracic spine. Although the morphologic, cytogenetic, and immunohistochemical stain profiles are characteristic of chordoma, this case was especially challenging given its location. Classical chordomas involve the thoracolumbar spine in less than 5% of cases, and chondroid chordoma is exceptionally rare in this location. This neoplasm also expressed immunoreactivity for calretinin, a finding not previously reported in chordomas. In the thoracic region, calretinin positivity raises the possibility of mesothelioma. Embryologically, the notochord induces development of the central nervous system. As S100 protein and calretinin are both calcium-binding proteins initially isolated from cells in the central nervous system, coexpression of S100 protein and calretinin may prove useful in the diagnosis of chordomas and warrants further study.

Normal Articular Cartilage of the Femoral Head in Octogenarians and Nonagenarians: A Report of 53 Patients Who Presented With Femoral Neck Fracture

(Poster No. 30)

Cesar V. Reyes, MD (creyes@morrishospital.org). Department of Pathology, Morris Hospital, Morris, Ill.

Context: As with most joints, degenerative joint disease of the femoral head is associated with aging, as well as with trauma or occupational injury. Age-related arthritis commences at age 50 years or older and is observed in about 80% of the population by age 65 years. Its absence at ages 80 and 90 is unusual. This abstract describes 53 octogenarians and nonagenarians who presented with femoral neck fracture and proved to have normal femoral head cartilage.

Design: During a 6-year period, from 2002 to 2007, at a small community hospital, 53 (95%) of 56 octogenarians and nonagenarians who had femoral neck fracture showed normal femoral head cartilage radiologically, pathologically, and microscopically. The female-male ratio of patients was 6:1.

Results: Osteopenia and osteoporosis appeared to be the cause in most of the cases, along with osteonecrosis (n = 2) and metastatic adenocarcinoma (n = 1). The femoral neck fracture is brought about by accidental slip or fall or simply by hip motion during ambulation. The primary risk factors for falling are poor balance, taking more than 4 prescription medicines, and muscle weakness. Elderly people with all 3 risk factors have almost a 100% chance of falling in a year. Those without these risk factors have a 12% chance; those without hip arthritic pains are usually active, less mindful of falling, and more prone to hip fracture. Female patients predominated because of their lower bone mass, lower bone density, and higher frequency of falling.

Conclusions: Normal femoral head articular cartilage in octogenarians and nonagenarians may not be unusual.

Bilateral Ovarian Metastases of Clear Cell Sarcoma of Tendons and Aponeuroses

(Poster No. 31)

Summer L. Nugent, MD (summerlindsay@gmail.com); Daniel C. Dim, MD; Olga B. Ioffe, MD. Department of Pathology, University ofMaryland, Baltimore.

Clear cell sarcoma of tendons and aponeuroses, also known as malignant melanoma of soft parts, was first described by Enzinger in 1965 and constitutes less than 1% of all soft tissue sarcomas. It has a predilection for the tendons of the foot and ankle region and has a propensity to most commonly metastasize to bone, lymph nodes, and lung but rarely to skin, liver, heart, and brain. We present the first case of a patient with clear cell sarcoma of tendons and aponeuroses in the foot who was found to have bilateral metastases to the ovaries 3 years after her initial diagnosis. The neoplastic cells stained with periodic acid-Schiff resistant to digestion with diastase showed cytoplasmic positivity for HMB-45 but were negative for S100 protein and MART-1 (Ventana, Tucson, Ariz). Molecular cytogenetic studies by fluorescence in situ hybridization demonstrated a translocation of the EWSR1 gene region at chromosome 22q12 in 94% (abnormal range for this probe is 15%-100%) of the paraffin-embedded specimen (Vysis Inc, Des Plaines, Ill). This is the first documented case of metastasis of clear cell sarcoma of tendons and aponeuroses to the ovaries.

Giant Cell Tumor of Bone With Unusual Presentation (Thoracic Vertebral) and Unusual Association (Cystic Angiomatosis)

(Poster No. 32)

Jinesh Patel, MD1 (jpatel3@metrohealth.org); S. Michael Thompson, MD2; Santhi Ganesan, MD.1 1Department of Pathology,MetroHealthMedical Center, Case Western Reserve University, Cleveland, Ohio; 2Department of Pathology, Summa Health System, Akron, Ohio.

We report an unusual presentation and association of giant cell tumor (GCT) in a 57-year-old man with multiple lytic lesions of appendicular and axial skeleton. Laboratory findings provided no evidence of hematologic or metabolic disease. Radiologic examination of the axial skeleton demonstrated a destructive mass involving the pedicle of the ninth thoracic vertebra with soft tissue extension. Excisional biopsy of the mass documented round to oval mononuclear cells and evenly distributed osteoclast-like giant cells that were consistent with GCT (Figure 26). Radiologic findings of appendicular lesions were consistent with cystic angiomatosis; the core biopsy of which yielded only blood (to exclude entities such as myeloma and metastases). GCT is a rare primary tumor of bone affecting the epiphysis of long bones. Thoracic spine involvement occurs in 2.5% of GCTs. There are no reported associations of GCT with bone and skeletal cystic angiomatosis. Differential diagnosis for multiple lytic bone lesions includes metastases, myeloma, eosinophilic granuloma, and hyperparathyroidism, among others. The lytic lesion of GCT of bone is due to independent bone resorption by neoplastic stromal cells or is mediated through a matrix metalloproteinase pathway. Cystic angiomatosis is considered to be a congenital or hamartomatous lesion of multicentric origin. These disorders seem to represent 2 independent pathologic entities; however, their coexistence in this case raises interesting questions, such as whether they represent a biologic continuum or have any possible link in pathogenesis. Clinical follow-up and molecular diagnostic modalities are needed to resolve this further.

Mixed Chondroblastoma-Chondromyxoid Fibroma of the Thoracic Vertebra

(Poster No. 33)

Vladislav Zakharov,MD1 (vladislav-zakharov@ouhsc.edu); EricH. Sincoff, MD2; A. Kevin Raymond, MD3; Kar-Ming Fung, MD, PhD.1 Departments of 1Pathology and 2Neurosurgery, University of Oklahoma, Health Sciences Center, Oklahoma City; 3Department of Pathology, University of Texas M. D. Anderson Cancer Center, Houston.

Chondroblastoma is an uncommon, benign, cartilaginous neoplasm that characteristically arises in the epiphyses of long bones in young patients and accounts for approximately 1% of all primary bone tumors.We present a case of chondroblastoma arising in an unusual location; the posterior elements of a thoracic vertebra. A 25-year-old man presented with back pain and numbness in the lower extremities for 8 weeks. Magnetic resonance imaging of the thoracic spine revealed a 5.0 3.3 2.0-cm posterior extradural enhancing mass, with dural enhancement. Computed axial tomography showed an expansile, destructive, largely unmineralized lesion arising from the posterior elements of T-7 with heterogeneous enhancement and central necrosis, and extending anteriorly into the epidural space causing cord compression. Radiologic differential diagnoses included aneurysmal bone cyst, osteoblastoma and less likely Ewing sarcoma, osteosarcoma, and lymphoma. Histologically, there were multiple fragments of neoplastic tissue with a substantial chondroid component with scattered calcifying islands. The level of cytologic atypia was low; mitotic figures were not readily seen. Areas with fibromyxoid components and entrapped adipose tissue suggestive of tumor invasion into surrounding adipose tissue were also present. The cytologic/histologic features are best interpreted as chondroblastoma with chondromyxoid fibroma-like differentiation. The vertebral location is atypical for chondroblastoma. The calcifying islands together with largely eosinophilic appearance of chondroblastoma-produced cartilage matrix may, particularly in frozen sections and small biopsies, suggest a diagnosis of osteosarcoma. Thorough sampling, clinical correlation and a working knowledge of the diversity of primary bone tumors are important for the diagnosis of these tumors.

Myelolipoma With Rosai-Dorfman-like Features: Report of a Case and Review of the Literature

(Poster No. 34)

Jose M. Gonzalez-Berjon, MD (jmgonzalezb@yahoo.com); Jared M. Gardner, MD; Alberto G. Ayala, MD. Department of Pathology, The Methodist Hospital, Houston, Tex.

Myelolipoma is a benign tumor composed of mature adipose tissue admixed with hematopoietic elements. This entity generally presents as a unilateral mass involving the adrenal gland. Rosai-Dorfman disease is typically characterized by massive lymphadenopathy with sinus histiocytosis, but extranodal involvement is present in up to 25% of the cases. We report a case of a giant myelolipoma with morphologic features of Rosai-Dorfman disease. A 37-year-old man presented with abdominal distention and pain. A retroperitoneal mass was discovered on abdominal computed tomography. Five months after initial presentation, the patient returned to clinic with weight loss, fever, increased abdominal girth, and dyspnea. Physical examination revealed rigid, distended abdomen with flank tenderness. Biopsy revealed extramedullary hematopoiesis. During surgery, a 30-cm, 6350-g encapsulated mass was entirely resected. The tan-yellow heterogeneous tumor completely enveloped and compressed the kidney. The mass was composed of mature adipose tissue with areas of trilineage hematopoietic cells. Additionally, peculiar giant mononuclear histiocytes with intracytoplasmic mature lymphocytes and erythrocytes (emperipolesis) were seen in areas of the tumor. S100 protein immunostain was focally positive in the giant histiocytes. The kidney was uninvolved. The patient recovered uneventfully. This lesion has a classic pattern of a myelolipoma and is associated with a Rosai-Dorfman proliferation. To our knowledge, there has not been a report describing this association. Because the diagnosis of Rosai-Dorfman disease may be open to question, we have elected to refer to it as Rosai-Dorfman-like proliferation.

Primary Oxalosis With Rapidly Progressive Bilateral Lower Extremity Ischemia

(Poster No. 35)

Renu Khode, MD (rekhode@swmail.sw.org); Robert S. Beissner, MD, PhD; Lisa M. Lopez, MD. Department of Pathology, Scott and White Hospital, Temple, Tex.

Primary hyperoxaluria encompasses 3 rare genetic disorders of glyoxylate metabolism characterized by excessive urinary excretion of oxalic acid resulting in oxalosis. Oxalate crystals commonly deposit in the kidney, followed by the heart, walls of arteries and veins, bone, and skin. We report a 45-year-old woman who presented with pain, bluish discoloration, and decreased temperature of both lower extremities. A clinical differential diagnosis of thrombosis, cholesterol emboli, or vasculitis was considered. Magnetic resonance angiography detected multifocal highgrade stenosis involving the bilateral iliac arteries. Because the patient's muscle necrosis rapidly progressed to gangrene, right above-knee and left through-knee amputations were performed. Gross examination revealed purple discoloration and petechiae of the skin with muscle necrosis, and thickening of the anterior tibial, posterior tibial, and popliteal vessels. Microscopy showed extensive muscle necrosis. The aforementioned arteries had diffuse subintimal fibrosis with golden yellow, birefringent, polarizable crystals suggestive of oxalate deposition. Our case illustrates that vascular oxalate deposition can mimic either vasculitis or thrombus due to its acute presentation. This is a very unusual presentation of primary oxalosis. Digital infarcts have been reported with livedo reticularis; however, bilateral lower extremity amputation due to rapid progression of the disease has been reported in only one other case in literature, to the best of our knowledge.

Can p16 Immunoreactivity Distinguish Between Well-Differentiated Liposarcoma and Pleomorphic Lipoma?

(Poster No. 36)

Michiko Nagamine, MD (michiko.nagamine@uphs.upenn.edu); Keith G. Danielson, PhD; John J. Brooks, MD. Department of Pathology, Pennsylvania Hospital of the University of Pennsylvania Health System, Philadelphia.

Context: Epigenetic alteration of p16 occurs in liposarcoma (LPS), including well-differentiated and dedifferentiated components, but not in lipomas. By immunohistochemistry, p16 nuclear staining has been found in both well-differentiated and dedifferentiated LPS. We tested the hypothesis that p16 reactivity may distinguish between LPS and its benign mimics, pleomorphic lipoma (PL) and spindle cell lipoma (SCL).

Design: The surgical pathology files were searched for lipomas (PL and SCL) and liposarcoma (atypical lipomatous tumor/well-differentiated liposarcoma [ALT/WD-LPS] and dedifferentiated [DD-LPS]). Using an antibody to p16 (Cell Marque, clone 16p04; prediluted) on the Ventana BenchmarkXT, with antigen retrieval (Tris/EDTA), immunohistochemistry was performed on 26 cases. Only nuclear reactivity was recorded, and frequency was scored as 0% to κ5% (rare/focal), 6% to κ25% (1+), 26% to κ50% (2+), and 50% (3+, diffuse).

Results: Control tissue (lung non-small cell carcinoma) had appropriate diffuse nuclear positivity. In ALT/WD-LPS, 11 (100%) of 11 caseswere positive, 2+ to 3+; 3 (100%) of 3 DD-LPS were positive, 1+ to 3+. In PL, 4 (100%) of 4 cases had 3+ reactivity; however, in SCL, 4 (66%) of 6 cases were negative; 2 cases showed 2+ reactivity. Two lipoma variants (fibrotic and hemosiderotic) were negative.

Conclusions: Strong, diffuse 3+ immunoreactive p16 was identified in both lipoma variants (PL, SCL) and liposarcoma. p16 immunoreactivity may be affected by processes other than epigenetic alterations. At least some SCLs differ from PLs despite being considered related entities. This marker is not useful in the differential diagnosis of lipomatous tumors with spindled or pleomorphic features.

AIDS-Related Kaposi Sarcoma and Angiosarcoma

(Poster No. 37)

Alicia Calderon, DO (amcalder@uci.edu); Fritz Lin, MD. Department of Pathology, University of California at Irvine, Orange.

Although Kaposi sarcoma and angiosarcoma are both malignant vascular neoplasms, they differ morphologically. Most Kaposi sarcomas are AIDS related, while their association with an angiosarcoma is controversial because the oncogenic virus is seldom observed in angiosarcomas.We report a case in which a 46-year-old man with AIDS was found to have a popliteal mass. Biopsy showed typical morphologic evidence of a Kaposi sarcoma. An interesting finding was that the Kaposi sarcoma merged imperceptibly into morphologic evidence of a classic low-grade angiosarcoma (Figure 27). In the upper left field of the figure are spindle cells with extravasated red blood cells depicting Kaposi sarcoma. The lower right field of the figure shows angiosarcoma. The neoplastic cells were immunoreactive for CD31 and CD34 (both immunoreagents from Dako, Carpinteria, Calif). The nuclei of both morphologic components were positive for HHV-8 oncogenic virus. A review of literature showed that the coexistence of Kaposi sarcoma and angiosarcoma is uncommon.

Utility of β-Catenin in Evaluating Surgical Resection Margins in Desmoid Tumors

(Poster No. 38)

Jerad M. Gardner, MD (zao275@gmail.com); Jae Y. Ro, MD, PhD; Luan D. Truong, MD; Qihui J. Zhai, MD. Department of Pathology, The Methodist Hospital, Houston, Tex.

Context: β-Catenin stimulates cellular proliferation via the Wnt pathway. Desmoid tumor is a locally aggressive mesenchymal neoplasm that requires negative surgical margins to prevent recurrence. Margins may be difficult to assess due to bland tumor cytology. Nuclear staining for β-catenin is very sensitive and specific for desmoid tumors. The use of β-catenin staining to evaluate surgical margins in desmoid tumor has not been previously reported. We investigated the utility of β-catenin immunostaining in identifying tumor cells at margins previously diagnosed as free by hematoxylin-eosin alone.

Design: Sections from 50 cases of desmoid tumor were immunostained for β-catenin. Nine of 50 cases were originally diagnosed with free margins. All margin sections from these "free margin" cases were immunostained for β-catenin and evaluated for nuclear positivity in cells at the margins.

Results: Forty-eight (96%) of 50 cases of desmoid tumor showed nuclear β-catenin staining. Cells with nuclear staining were seen infiltrating resection margins in 6 (67%) of 9 cases from the free margin group. Clinical follow-up of these 6 patients found 1 patient with desmoid recurrence and 1 patient without recurrence (4 patients had either recent initial diagnosis or incomplete data).

Conclusions: Nuclear expression of β-catenin is a frequent finding in desmoid tumors in our series. β-Catenin immunostaining enabled us to identify desmoid tumors with positive margins that were previously diagnosed as negative by routine hematoxylin-eosin stain. Therefore, β-catenin immunostaining may be helpful in detecting foci of tumor cells involving the margins in cases where hematoxylin-eosin morphology is uncertain, subsequently enabling optimal patient treatment.

Fatal Amebic Encephalitis and Pulmonary Aspergillosis Following Autologous Stem Cell Transplantation

(Poster No. 39)

Robert M. Najarian, MD1 (rnajaria@bidmc.harvard.edu); Evan C. Miller, MD, MPH1; Scott Duong, MD1; Qinfang Qian, MD1; James E. Kirby, MD1; Jeffrey T. Joseph, MD, PhD.2 1Department of Pathology, Beth Israel Deaconess Medical Center, Boston, Mass; 2Department of Pathology, Foothills Medical Centre, Calgary, Alberta.

Infections with mycobacteria, fungi, and protozoa are rare in immunocompetent individuals but can present simultaneously in the immunocompromised. The patient was a 67-year-old man who was admitted for neutropenic fever 2 months after an autologous stem cell transplant for multiple myeloma. Chest imaging revealed multiple pulmonary nodules in connection with an infectious process. Sputum and bronchoalveolar lavage samples grew multiple gram-negative organisms including Moraxella and Stenotrophomonas species. The patient's clinical course became complicated by mental status changes, and magnetic resonance imaging showed a probable subacute infarct in the right medial occipital lobe and corpus callosum. The infarction progressed to massive intraparenchymal hemorrhage due to edema, uncal herniation, and lesions thought to represent septic emboli, and the patient died. At autopsy, a solitary, left upper lobe pulmonary lesion contained on microscopic examination numerous fungal organisms with acutely branching, septated hyphae that were morphologically consistent with Aspergillus species. This lesion and the remaining lung parenchyma contained minimally associated inflammation. Postmortem cultures confirmed the presence of Aspergillus fumigatus. Gross examination of the brain showed hemorrhagic areas of liquefactive necrosis in the right occipital lobe and left parietotemporal regions. Histologic examination revealed active amebic meningoencephalitis with numerous trophozoites and cysts, which were associated with prominent secondary intravascular inflammatory thrombi and necrosis (Figure 28). Immunocompromised patients, including stem cell transplant recipients, often present with complex clinical symptoms that do not "fit" a single diagnosis. These patients may present with multiple atypical organisms, which can complicate the workup. In terminal cases, an autopsy can identify previously unsuspected organisms.

Superior Sagittal Sinus Thrombosis With Intracranial Hemorrhage in a Patient With Sickle Cell Trait

(Poster No. 40)

Dian Feng, MD (dianfeng@buffalo.edu); Reid Heffner, MD. Department of Pathology, State University of New York at Buffalo, East Amherst.

Superior sagittal sinus thrombosis associated with sickle cell trait is exceedingly rare. We report an autopsy case of a 42-year-old African American man with sickle cell trait who died of bilateral pneumonia due to superior sagittal sinus thrombosis with intracranial hemorrhage. The clinical history and autopsy results of the patient were reported, and a review of the literature of sickle cell trait was undertaken. As noted, the patient was a 42-year-old African American man with sickle cell trait. He was visiting relatives in Buffalo, New York, when he suddenly experienced episodes of seizure activity and headaches. In the emergency department, a computed tomography scan revealed intracranial hemorrhage. On admission, an angiogram demonstrated superior sagittal sinus thrombosis. A mercy morcellation of the clot was attempted but failed. The patient developed hydrocephalus, and a ventriculoperitoneal shunt was placed. The patient died 6 weeks after admission. His mother is alive with sickle cell trait. Some of his relatives have sickle cell disease. Autopsy identified residual organizing thrombus and clots in the superior sagittal sinus. Two foci of intracranial hemorrhage were present in his bilateral hemispheres. Focal small infarcts were shown in the pons and the pituitary gland.Many sickle cells were seen in his liver and kidneys. His lungs showed bilateral bronchopneumonia. Cerebrovascular complications of sickle cell disease are well known, whereas cases associated with sickle cell trait are rare. Nevertheless, patients with sickle cell trait have an increased risk of cerebrovascular thrombosis. These patients should avoid hypoxia to protect themselves from complications.

Adult Onset Still Disease as a Possible Paraneoplastic Presentation of Occult Breast Carcinoma

(Poster No. 41)

Keyur Patel, MD, PhD; Abha Goyal, MD (agoyal1@nshs.edu); Tawfiqul Bhuiya, MD. Department of Pathology, North Shore Long Island Jewish Health System, New Hyde Park, NY.

Adult onset Still disease is a rare systemic inflammatory disorder of unknown etiology. The clinical presentation can be mimicked by various neoplastic, autoimmune, and infectious disorders. It has rarely been observed as a paraneoplastic manifestation of underlying malignancies including breast carcinoma. We report a case of adult onset Still disease that was diagnosed with occult breast carcinoma on autopsy. A 74-year-old woman presented with spiking fever, polyarthralgia, rash, and sore throat. Laboratory investigations revealed leukocytosis, elevated erythrocyte sedimentation rate, elevated serum ferritin, a negative antinuclear antibody, a negative rheumatoid factor, and deranged liver function tests. A chest x-ray and a computed tomography scan showed bilateral pleural effusions. Overall, her signs and symptoms were compatible with a diagnosis of adult onset Still disease. Her hospital course worsened with the development of atrial fibrillation. Autopsy findings included serofibrinous pericarditis and an old myocardial infarct. On gross examination, no breast mass was palpable. However, an axillary lymph node showed a focus of signet ring cell carcinoma, which was positive for GCDFP-15 and cytokeratin (CK) 7 and negative for CK20 on immunohistochemistry. These findings were consistent with metastatic breast carcinoma. Based on the few reports in literature, we postulate that her occult malignancy may have presented itself as a paraneoplastic syndrome in the form of adult onset Still disease. This case lends support to the possibility of an occult malignancy in a patient with adult onset Still disease.

Clinically Undetected Malignancy Identified at Autopsy: A Single Institution Review

(Poster No. 42)

Vanessa Phillips-Williams, MD (mvphillips-williams@mcvh-vcu.edu); Michael O. Idowu, MD; Margaret M. Grimes, MD; Hugh D. Massey, MD. Department of Pathology, Virginia Commonwealth University Health System, Richmond.

Context: Previous studies have demonstrated the value of the autopsy in the identification of clinically unsuspected pathology including malignancy. Nevertheless, there has been a decline in recent years in the performance of hospital autopsies in the United States. Some have attributed the decline to technologic advances in diagnostic techniques and to the common assumption that significant diseases will be diagnosed premortem. This study was conducted to determine the numbers of cases of clinically undetected malignancy identified at autopsy during the last 8 years at our institution.

Design: We reviewed all reports of autopsies performed at our institution during the 8-year period between January 2000 and December 2007. The number of cases with premortem malignant diagnoses and cases with malignancy diagnosed only at autopsy were compared with the total number of cases for each year.

Results: Records of 1017 autopsies were reviewed. Of these, 199 (19.6%) had premortem diagnoses of malignancy. In 67 (6.6%) of 1017 autopsies, malignancy was diagnosed at autopsy only. The annual percentage of autopsy cases with clinically undetected malignancy ranged from 3.4% to 9.2% (Table).

Conclusions: Despite the decline in total number of autopsies each year, there appears to be no reduction in the number of cases with postmortem diagnosis of malignancy. Our results demonstrate the continued value of the autopsy in detecting clinically undiagnosed malignancy.

Histiocytoid Cardiomyopathy: Report of a Case and Literature Review

(Poster No. 43)

Cyrus K. Manavi, MD1 (ckmanavi7@gmail.com); Henry D. Edwards, MD1; Patrick E. Lantx, MD1; John A. Papalas, MD.2 1Department of Pathology, Wake Forest University Baptist Medical Center, Winston Salem, NC; 2Department of Pathology, Duke University Medical Center, Durham, NC.

Histiocytoid cardiomyopathy is a rare arrhythmogenic cardiac condition of unknown etiology affecting young infants and children with a female predominance. This disease can manifest as sudden death in an otherwise healthy child. We report the pathologic features of an autopsy case and compare it with those previously published. We reviewed the English language literature representing approximately 70 reported cases from 1960 to 2008. Our patient was an otherwise healthy 1-year-old white girl who died suddenly and unexpectedly. At autopsy, the heart weighed 50 g. The epicardium was remarkable for 15 to 20 pale tan-yellow subepicardial nodules distributed along the midportion of the anterior septum. Nodules were also present on the mitral and tricuspid valves. Cross sections of the ventricles showed a diffuse subendocardial pallor. Histologically, the lesions were composed of cells with granular eosinophilic cytoplasm scattered throughout atria, ventricles, interventricular septum, and the conduction system (Figure 29). These cells were negative for CD68 and S100 and were faintly positive for periodic acid-Schiff and musclespecific actin. Histiocytoid cardiomyopathy is known to consist of altered myocardial cells that can precipitate fatal tachyarrhythmias. Compared with previous cases, our case has similar clinical and histologic features with the exception of simultaneous involvement of atria, ventricles, valves, and conduction system. Only one previously reported case has documented involvement of all of these locations in the absence of other congenital abnormalities.

Usefulness of Wright-Giemsa Stains to Detect Pseudomonas Infection

(Poster No. 44)

Liset Pelaez, MD (lpelaez@med.miami.edu); Carlos Parra-Herran, MD; Arnel K. Urbiztondo, MD; Maria M. Rodriguez, MD. Department of Pathology, University of Miami/Jackson Memorial Hospital, Miami, Fla.

Context: Preterm newborns are at increased risk for Pseudomonas infection because they are immunocompromised and often require mechanical ventilation, invasive maneuvers, and prolonged hospitalization.We herein describe the pathologic findings of Pseudomonas infection using Wright-Giemsa stains for microorganism identification.

Design: We reviewed neonatal autopsy reports with diagnosis of sepsis or pneumonia and selected patients with culture-proven Pseudomonas aeruginosa in blood, tracheal aspirate, or lung and histologic features of Pseudomonas infections confirmed by special stains.

Results: Of 249 autopsies, 7 (2.8%) had Pseudomonas pneumonia; 6 of them were in premature neonates. Gestational age ranged from 23 to 39 weeks. Average survival was 13.5 days. Premature rupture of membranes was present in 4 cases. Six cases had premortem clinical diagnosis of sepsis. Radiologic findings were unspecific. Two patients had significant leukopenia. Anemia and thrombocytopenia was found in 5 and 4 cases, respectively. Microscopy revealed tissue necrosis with scarce or absent inflammatory cells and necrotizing vasculitis. Only one case had intraalveolar neutrophilic infiltrates toward the periphery. Tissue Gram stain was negative in these patients. Wright-Giemsa stains demonstrated filamentous organisms inside blood vessels and within vascular walls. Two patients had disseminated Pseudomonas infection (Figure 30).

Conclusions: Tissue Gram stain is not helpful in confirming Pseudomonas infection. Radiologic findings are nonspecific for pneumonia in premature neonates. The findings of necrotizing vasculitis, a bluish color around blood vessels, and the absence of an inflammatory reaction are strongly suggestive of Pseudomonas infection. Wright-Giemsa stains are an inexpensive and excellent way to demonstrate the presence of Pseudomonas as perivascular, filamentous organisms in tissues.

Intestinal Candidiasis: An Uncommon Cause of Necrotizing Enterocolitis in Neonates

(Poster No. 45)

Carlos E. Parra-Herran, MD (cparraherran@med.miami.edu); Liset Pelaez, MD; Arnel K. Urbiztondo, MD; Maria M. Rodriguez, MD. Department of Pathology, University of Miami/Jackson Memorial Hospital, Miami, Fla.

Context: Candida albicans can cause intestinal perforation and necrotizing enterocolitis (NEC) in preterm babies. Our study defines the relevant clinicopathologic features of intestinal candidiasis in this group.

Design: We reviewed autopsy and surgical pathology files in neonates with sepsis as cause of death or diagnosis of NEC from a 10-year period. We gathered relevant perinatal information and reviewed the histologic material for each case.

Results: Of 249 autopsy reports, 41 (16%) had a diagnosis of sepsis; 3 (1.2%) had systemic candidiasis. From 66 surgical cases with clinical diagnosis of NEC/intestinal perforation, 6 (9%) cases had diagnosis of intestinal candidiasis. The average age was 16.7 days (SD, 8.6). Average gestational age was 24 weeks (SD, 1.62), and the average birth weight was 622 g (SD, 154). Premature rupture of membranes was documented in 4 (44%) of 9 cases. Candida albicans grew in premortem and postmortem blood, lung, or peritoneal fluid in all cases. Histologically, the small bowel revealed fungal aggregates occluding submucosal and serosal small- and middle-sized vessels (Figure 31). Necrosis was limited to the mucosa and was not associated with gas formation. Interestingly, inflammatory response was universally minimal to absent.

Conclusions: Systemic-intestinal candidiasis is an important complication of prematurity and a prevalent cause of sepsis. Absence of inflammatory response and presence of intravascular colonization of the gastrointestinal tract by C albicans was uniformly seen, suggesting that gastrointestinal candidiasis can be a cause of NEC. The presence of intraluminal fungi with associated vascular occlusion may lead to bowel ischemia, necrosis, and perforation.

Diffuse Large B-Cell Lymphoma With Extension Into the Inferior Vena Cava: A Clinical and Radiographic Mimic of Renal Cell Carcinoma

(Poster No. 46)

Kathi H. Adamson, MD1 (kathia@u.washington.edu); Corrine Fligner, MD1; Sindhu Cherian, MD2; Manjiri Dighe, MD3; John Thompson, MD.4 Departments of 1Pathology, 2Laboratory Medicine, 3Radiology, and 4Medicine, University of Washington, Seattle.

Tumor extension into large vessels is not characteristic of malignant lymphoma. Renal cell carcinoma commonly extends into the inferior vena cava as "tumor thrombus," and such involvement occurs occasionally with pheochromocytoma, adrenal cortical carcinoma, hepatocellular carcinoma, and occasional sarcomas. A 64-year-old man with a 3-month history of fatigue, hematuria, sacral and left hip pain, and lower extremity edema was found on computed tomography scan to have a right kidney mass with an inferior vena cava tumor thrombus. Additional imaging demonstrated pathologic fracture in the left pelvis and tumor mass in the left adrenal, prompting the clinical diagnosis of metastatic renal cell carcinoma. No biopsy was performed. He died 12 days after admission after electing comfort care. At autopsy, the right kidney contained a 20-cm, multinodular white tumor with perirenal fat extension and hydronephrosis. The tumor extended into renal vein and 7 cm into the inferior vena cava and was present in the left adrenal and adjacent to and in the left pubic bone. Histology confirmed a diagnosis of diffuse large B-cell lymphoma (CD20 positive, Pax-5 and CD10 weakly positive, and Ki-67 variably positive up to 70%). There was no microscopic small vessel intravascular lymphoma. Microscopic lymphoma was present in an accessory spleen and 1 peripancreatic lymph node; there was no lymphadenopathy or other axial bone marrow involvement. Large vessel extension of malignant lymphoma is relatively unusual in any site. Radiologic identification of large vessel extension by a renal neoplasm does not exclude the diagnosis of malignant lymphoma.

Dedifferentiated Liposarcoma With Peculiar Meningothelial-like Whorling and Metaplastic Bone Formation: A Report of 2 Cases

(Poster No. 47)

William P. Tarrant, MD (wptarrant@tmhs.org); Joon Seon Song, MD; Jerad Gardner, MD; Steven Shen, MD, PhD; Alberto G. Ayala, MD; Eunsil Yu, MD, PhD; Jae Y. Ro, MD, PhD. Department of Pathology, The Methodist Hospital, Houston, Tex.

Dedifferentiated liposarcoma with peculiar meningothelial-like whorling pattern and metaplastic bone formation (DDLMB) is an unusual morphologic entity characterized by an atypical lipomatous tumor with meningothelial-like "whorls" of epithelioid or spindle cells and mature bone trabeculae rimmed by osteoblasts. Only 34 cases of DDLMB have been reported in the literature. Although paraganglioma-like pattern has been described in dedifferentiated liposarcoma, it has not been previously reported in DDLMB. We report 2 cases of DDLMB, one of which contains a paraganglioma-like tumor component. In case 1, a 64-year-old man presented with a 3.5-cm painless groin mass, which was clinically diagnosed as cord lipoma. In case 2, a 42-year-old woman presented with a painless abdominal mass; abdominal computed tomography scan showed an 18-cm retroperitoneal mass clinically suspicious for sarcoma. Both tumors were subsequently resected. In both cases, microscopic features of atypical lipomatous tumor with meningothelial-like whorls and metaplastic bone formation were seen. Additionally, focal paraganglioma-like pattern was seen in case 1; pleomorphic sarcoma and low-grade myxofibrosarcomalike areas were seen in case 2. Immunohistochemically, the meningothelial-like and paraganglioma-like DDLMB tumor components were positive for vimentin and CD56 and negative for pancytokeratin, epithelial membrane antigen, desmin, and smooth muscle actin. Characteristically, the paraganglioma-like area was immunoreactive for S100 protein with a "dot-like" staining pattern. To our knowledge, case 1 represents the first report of DDLMB with paraganglioma-like pattern. Recognition of the possible morphologic variants of dedifferentiated liposarcoma will enable accurate diagnosis of this entity.

Recurrent Blastomycotic Meningitis Following Cerebellar Resection in a Patient Without Risk Factors

(Poster No. 48)

Jeffrey S. Hudson, MD (jeffrey.hudson@utoledo.edu); John H. Irlam, DO; Amira Gohara, MD. Department of Pathology, University of Toledo Medical Center, Toledo, Ohio.

Blastomycosis is a fungus that is abundant in nature. However, central nervous system infections are rare in nonimmunocompromised individuals. It is invariably seen in patients with immunodeficiency syndromes or immunosuppressive drug use. In the absence of these risk factors, blastomycosis is removed from the differential. We present an autopsy case of a 21-year-old woman with recurrent, isolated blastomycosismeningitis without known predisposing factors. In January 2006, our patient experienced an episode of loss of consciousness and was found to have a brain mass. The mass was resected and was found to be a blastomycotic infection. She was treated with antifungal therapy for 2 weeks followed by oral medication for 1 month. She did well until August of 2007 when she presented to the hospital with a 4-day history of headaches, photophobia, and intermittent fevers. Cerebrospinal fluid analysis was consistent with meningitis, and aggressive therapy was begun. Despite maximum medical effort, her condition rapidly deteriorated, and she died 5 days later. Autopsy was performed including an evaluation for human immunodeficiency virus and other immunodeficiency syndromes. Gross findings included liquefactive necrosis in the left cerebellum and severe brain edema (1500 g). The most significant microscopic finding was the presence of blastomycotic yeast within the left cerebellum and brainstem (Figure 32). Our patient suffered from a recurrent blastomycotic meningitis that led to her death. This is rare, especially for an individual without known immunodeficiency. We offer that there are predisposing factors to blastomycotic infections that have not yet been elucidated, and further investigation is needed to describe them.

Cysteine-X-Cysteine Chemokine Ligand 10 Inhibits Virus Replication Through Recruitment of Natural Killer Cells in Coxsackievirus B3-Induced Myocarditis

(Poster No. 49)

Ji Yuan, BM (jyuan@mrl.ubc.ca); Travis Lim, MSc; Jianqing He, BM; Elizabeth Walker, BM; Courtney Shier, MD; Yinjing Wang, BM; Huifang Zhang, MSc; Alhousseynou Sall, PhD; Zhen Liu, MSc; Bruce McManus, MD, PhD; Decheng Yang, PhD. Department of Pathology, iCAPTURE Centre-University of British Columbia, Vancouver.

Context: Coxsackievirus B3 (CVB3) is the primary cause of viral myocarditis. The role of cysteine-x-cysteine (CXC) chemokine ligand 10 (CXCL10, formerly interferon-inducible protein 10) in CVB3-induced myocarditis is unknown.

Design: To explore the contribution of CXCL10 to CVB3-induced myocarditis, we performed functional analyses using newly generated transgenic mice with cardiac-specific CXCL10 overexpression and CXCL10 knockout mice.

Results: Following CVB3 challenges, the viral titer in the mouse hearts inversely correlated with the levels of CXCL10 at early phase of infection prior to the visible immune infiltration. Furthermore, in contrast to results in the control mice, the decreased virus titers in the CXCL10 transgenic mouse hearts led to less cardiac damage, as indicated by low serum cardiac troponin I levels and better cardiac functional performance, while the results were the other way around in the knockout mice. This antiviral ability of CXCL10 might be through recruitment of natural killer cells to the heart and increased interferon-expression early in infection. On the seventh day of the infection, with a massive influx of mononuclear cells, the expression of CXCL10 enhanced the infiltration of CXCR3-positive cells, CD4- and CD8-positive T cells, and associated inflammatory cytokines. However, the augmented accumulation of these immune cells and associated cytokines failed to alter viral clearance and mice survival.

Conclusions: These results suggest the protective role of CXCL10 during the early course of CVB3 infection due to the recruitment of natural killer cells. Nonetheless, CXCL10-directed chemoattractant effect is not sufficient for the host to clear the virus in the heart.

Myocardial Mast Cell Distribution in Cardiovascular Disease

(Poster No. 50)

John C. Lee, MD1 (jlee800@yahoo.com); Tara C. Williams, MD1; Jacob Joseph, MD2; Lija Joseph, MD.1 Departments of 1Pathology and 2Medicine, Boston Medical Center, Boston, Mass.

Context: Studies have demonstrated the importance of myocardial mast cells in hypertensive and coronary artery disease. These studies have evaluated mast cells only within the left ventricle. We evaluated the distribution of mast cells in all 4 chambers of the heart from autopsy patients with cardiovascular disease.

Design: Autopsy patients from Boston Medical Center between 2006 to 2007 with hypertensive or coronary artery disease were identified. Tissue blocks from all 4 heart chambers were stained with toluidine blue and CD117 to identify mast cells. Mast cells were counted per high-power field for the entire tissue section. Statistical analysis was performed utilizing Sigmastat 3.0 (Aspire Software International, Ashburn, Va) to examine for significant correlations of mast cell number with age, sex, heart chamber, heart weight, and hypertensive or coronary artery disease.

Results: There was a significant correlation between mast cell numbers identified by toluidine blue and CD117 staining (P < .001). However, CD117 identified significantly more mast cells (mean, 5) compared with toluidine blue (mean, 1.5). Mast cell numbers were greater in the ventricles compared with the atria (Table). There was a significant correlation between mast cell numbers in all 4 cardiac chambers in each patient. There were no significant correlations between mast cell numbers with age, sex, heart weight, or cardiovascular diagnosis.

Conclusions: This is the first study evaluating the distribution of mast cells in autopsy patients with cardiovascular disease. Mast cell density is greatest in the ventricles compared with the atria.

POSTER SESSION 400: FRIDAY, SEPTEMBER 26, 2008, 1:30 PM-4:00 PM

Cytopathology; Breast Pathology; Dermatopathology; Endocrine Pathology; Administrative and Regulatory Affairs

The Utility of ThinPrep Monolayer Preparation in the Evaluation of Thyroid Lesions by Fine-Needle Aspiration Biopsy: Comparison With Conventional Smear Method

(Poster No. 1)

Husain A. Saleh, MD, FIAC, MBA1 (hsaleh@dmc.org); Nader Bassily, MD2; Jamal Hammoud, MD, FACE.3 1Department of Pathology, Wayne State University, Detroit, Mich; Departments of 2Pathology and 3Endocrinology, Michigan State University, Flint.

Context: We retrospectively compared the diagnostic accuracy and cytomorphologic features of thyroid lesions on ThinPrep monolayer preparation (TP) with those of conventional smear method (CS) on fine-needle aspiration biopsy.

Design: Slides of 145 TP and 145 CS consecutive thyroid fine-needle aspiration biopsy cases were retrospectively reviewed for amount and architecture of follicular cells, nuclear and cytoplasmic details, amount and quality of colloid, background blood, cyst fluid, and macrophages, and lymphocytes and plasma cells.

Results: TP slides more often had higher cellularity with flat clusters, whereas CS slides more often had 3-dimensional clusters. CS slides displayed better follicular cell morphology, whereas TP slides revealed shrunken cells with fragmented cytoplasm and dark naked nuclei. Colloid was more abundant on CS slides, whereas it appeared as small dense droplets (thick colloid) or as folded tissue paper-like material (thin colloid) on TP slides. CS slides more often had obscuring bloody background, whereas TP slides had clear background. Both methods had similar diagnostic rates for chronic thyroiditis (11% TP vs 12% CS) and atypical/neoplastic lesions (3.4% each). TP had a slightly better diagnostic rate for colloid nodules (49% TP vs 45.5% CS), and the nondiagnostic rate was lower in TP (24%) than in CS (31%) slides.

Conclusions: Although there are cytomorphologic differences between TP and CS, TP method shows a lower nondiagnostic rate, a similar diagnostic rate for chronic thyroiditis and atypical/neoplastic lesions, and a slightly better diagnostic rate for colloid nodules. We believe that the 2 methods complement each other and should both be performed on all thyroid fine-needle aspiration biopsy cases.

Lack of Sensitivity of Hybrid Capture High-Risk Human Papillomavirus Testing in Detecting Cervical Dysplasia When Used in Conjunction With Conventional Cervical Cytology

(Poster No. 2)

John K. Joseph, MD1 (jkjoseph@bcm.edu); Linda K. Green, MD.1,2 1Department of Pathology, Baylor College of Medicine, Houston, Tex; 2Michael E. Debakey Veterans Affairs Medical Center, Houston, Tex.

Context: Human papillomavirus (HPV) types 16 and 18 are reportedly present in 80% of patients with cervical dysplasia. When combined with cytology, patients with atypical squamous cells of undetermined significance (ASC-US) or squamous intraepithelial lesion (SIL) and positive high-risk (HR)-HPV testing are triaged to colposcopy. Most of the data regarding the utility of this method have been based on liquid-based cytology. However, conventional cervical smears are still commonly used. We report our institution's experience using hybrid capture HR-HPV testing with conventional Papanicolaou tests in identifying dysplasia.

Design: All cervical biopsies in 2007 were reviewed for cervical intraepithelial neoplasia (CIN) 1 through 3. The cases identifiedwere reviewed. The corresponding cervical smears, HR-HPV testing, and clinical findings were correlated from the clinical records.

Results: There were 93 CIN 1 cases (cytology: low-grade squamous intraepithelial lesions 80%, ASC-US 19%, and negative 1%) and 20 CIN 2 and 3 cases (cytology: low-grade squamous intraepithelial lesions 65%, ASC-US 20%, no smear 10%, and high-grade squamous intraepithelial lesions 5%) in 113 colposcopies. HR-HPV testing was performed in 57% of the CIN 1 cases (43% positive) and 16% of the CIN 2 and 3 cases (only 50% positive).

Conclusions: HR-HPV testing in combination with conventional cervical smears is far less sensitive than liquid-based cytology, and cytology diagnosis was superior to identifying dysplasia. Decisions based on HRHPV testing should be made with extreme caution.

Fine-Needle Aspiration of a Liver Mass in a Patient With Chronic Myelogenous Leukemia, Neutrophilic Variant

(Poster No. 3)

Majd Jundi, MD (majdjundi@yahoo.com); Syed Salahuddin Ahmed, MD. Department of Pathology, Al-Hada Armed Forces Hospital, Taif, Saudi Arabia.

We are reporting an unusual presentation of a patient with neutrophilic variant of chronic myelogenous leukemia (CML). This is an 80-year-old Sudanese man who was previously diagnosed with CML, neutrophilic variant, based on bone marrow study and molecular cytogenetic analysis of peripheral blood that proved the presence of BCR-ABL transformation. The patient was admitted to our hospital for generalized fatigue and rightsided weakness of 2 days' duration. He was found to have a liver mass in the left lobe measuring 16.0 14.6 cm with heterogenous echo texture and a smaller well-defined lesion in the right lobe measuring 2.0 2.0 cm. Computed tomography-guided fine-needle aspiration was performed on the left lobe lesion. Smears showed many mature neutrophils with no background necrosis, and the diagnosis was liver infiltration by the neoplastic neutrophils. Neutrophilic variant of CML is a rare subtype of CML that is differentiated from chronic neutrophilic leukemia by its association with BCR-ABL transformation. We are unaware of any reported cases of tissue infitration by the mature neutrophils in those patients.

Fine-Needle Aspiration of Metastatic Renal Cell Carcinoma to the Thyroid: A Study of 2 Cases and Review of the Literature

(Poster No. 4)

Ji-Weon Park, MD1 (jiwpark@notes.cc.sunysb.edu); Timothy Pal, MD1; Seth Klein, MD2; James Magidson, MD1; Alan Heimann, MD.1 Departments of 1Pathology and 2Radiology, Stony Brook UniversityMedical Center, Stony Brook, NY.

Tumors rarely metastasize to the thyroid gland. Specifically, the rate of renal cell carcinoma (RCC) spread to the thyroid is less than 0.1%. Cytologic characteristics of metastatic RCC and primary thyroid tumorsmay overlap, presenting a diagnostic dilemma during examination of fine-needle aspirates. We present 2 cases of metastatic RCC to the thyroid. The first patient is a 57-year-old man whose ultrasound was interpreted as multinodular goiter. The aspiration showed cells suspicious for papillary carcinoma. Subsequent surgical excision confirmed papillary carcinoma, but it also revealed a small nodule of metastatic RCC intermingled with the papillary carcinoma. The second patient is a 71-year-old woman whose ultrasound showed a dominant mass replacing most of the right lobe. The aspiration had cells that were indeterminant between RCC and papillary carcinoma. Immunohistochemistry performed on the aspirate confirmed the renal cell origin. The surgical specimen revealed a large nodule of metastatic RCC and incidental microscopic foci of papillary carcinoma in the opposite lobe. Although both patients presented with a thyroid mass and a history of RCC, they had variable imaging and cytologic interpretation of the fine-needle aspiration specimens. Because of the rarity of tumor metastases to the thyroid, primary tumor is usually higher in the differential. This study emphasizes that metastasis must be considered part of the differential diagnosis of a thyroid lesion in a patient with a history of RCC. Appropriate clinical history, imaging, and immunohistochemical analysis of cellular material will suggest appropriate surgical management.

Fine-Needle Aspiration Cytology of Lymph Nodes: Lessons Learned From 16 Years of Experience

(Poster No. 5)

Keyur Patel, MD, PhD (kpatel1@lij.edu); Antonio Macias, MD; Chiara Sugrue, MS, SCT(ASCP); Patricia Wasserman, MD. Department of Pathology, Long Island Jewish Medical Center, New Hyde Park, NY.

Context: The use of lymph node (LN) fine-needle aspiration as a diagnostic procedure has been steadily increasing. However, the procedure is still associated with several limitations and diagnostic pitfalls. We report important lessons learned from the analysis of our 16-year cumulative experience with LN aspirations.

Design: A comprehensive analysis of 1610 LN aspirations performed at our institute from 1990 to 2005 was performed. Thirty-nine fields of related information were collected for each case. Analysis was performed using Microsoft Excel spreadsheet.

Results: Overall, metastatic malignancies (533 cases [33%]) and reactive enlargements (528 cases [33%]) constituted the most frequent diagnoses, followed by lymphoproliferative disorders (256 cases [16%]) and infectious/inflammatory diseases (26 cases [2%]). The following combinations of sensitivity and specificity, respectively, were obtained in 4 diagnostic categories: reactive (99%, 78%), inflammatory (100%, 80%), metastatic (88%, 96%), and lymphoma (66%, 89%). Unique site-specific disease distribution was observed. Overall, the lymphoproliferative disorders accounted for most false-negative and false-positive diagnoses. Of the 256 lymphoproliferative lesions, 179 cases (70%) were accurately diagnosed as lymphoma, whereas 77 cases (30%) were suspicious but not diagnostic for lymphoma. Accurate subtyping was obtained in 82% of lymphoma cases. The majority (67/96) of pediatric cases showed reactive changes. Sampling technique was the most frequent source of error.

Conclusions: The results of this study confirm the value of fine-needle aspiration as an effective tool for the initial diagnosis of lymphadenopathy. Onsite evaluation with appropriate triage of the initial aspirate and judicial use of ancillary techniques greatly enhance utility of the procedure.

High-Risk Human Papillomavirus Testing in Women With Atypical Squamous Cells, Cannot Exclude High-Grade Squamous Intraepithelial Lesion

(Poster No. 6)

Sara M. Shunkwiler, MD (shunsm@pathology.ufl.edu); Andrew H. Fletcher, MD; Edward J. Wilkinson, MD. Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville.

Context: The American Society for Colposcopy and Cervical Pathology 2006 consensus guidelines state that women with atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H) should be referred for colposcopy. If no high-grade cervical intraepithelial neoplasia (CIN) 2 or 3 is identified, management consists of repeat cytologic examinations at 6 and 12 months and/or high-risk human papillomavirus (HPV) testing at 12 months. In this study, we examine triage HPV testing in ASC-H patients and subsequent colposcopic diagnoses.

Design: Cytopathology records at the University of Florida/Shands were reviewed from January 1, 2003, to December 31, 2007, to identify patients with ASC-H. Subsequent colposcopic diagnoses were examined in addition to any results of oncogenic HPV testing.

Results: A total of 210 patients with ASC-H were identified: 154 patients with no HPV testing performed and 56 patients with HPV testing obtained. Colposcopy was performed on 98 patients with no HPV testing and on 30 patients with HPV test results available. χ^sup 2^ probability was 0.023 (P = .02). χ^sup 2^ was 11.3 (Table).

Conclusions: While the American Society for Colposcopy and Cervical Pathology 2006 guidelines state that patients with ASC-H should proceed to colposcopy, our data indicate a possible role for triage HPV testing. Of those ASC-H patients testing negative for HPV, no cases of CIN 2/3 were diagnosed, 33% had CIN 1, and 66% were benign. Of those ASC-H patients testing positive for HPV, 56% had CIN 2/3, 6% had CIN 1, and 39% were benign. These differences are statistically significant (P = .02).

Decidualized Endometrioma Diagnosed by Fine-Needle Aspiration Cytology: A Case Report With Immunocytochemical Confirmation

(Poster No. 7)

Yasser M. EL-Gohary, MD (ygohary@yahoo.com); Monica T. Garcia, MD; Parvin Ganjei-Azar, MD. Department of Pathology, Jackson Memorial Hospital/University of Miami Miller School of Medicine, Miami, Fla.

Cutaneous decidualized endometriosis is rare. Here, we report the second case in the cytology literature of this uncommon pathologic entity with immunocytochemical confirmation which was not reported previously. A pregnant woman presented with a lower anterior abdominalwall mass located underneath a previous cesarean delivery scar. The clinical impression was desmoid tumor. Fine-needle aspiration was performed. The Papanicolaou-stained slides were stained with monoclonal CD10 (Leica, Bannockburn, Ill) and estrogen receptor (ER) (Dako, Glostrup, Denmark) without destaining. The specimen consisted predominantly of decidualized stromal cells, which were rounded or polygonal, had dense amphophilic epithelioid cytoplasm, central or eccentric nuclei with fine chromatin, single prominent chromocenters, and were arranged in loosely cohesive groups. Prominent blood vessels were identified streaking through the groups of decidual cells (Figure 33). Abundant hemosiderinladen macrophages and a group of endometrial glandular cells were also observed. No cytologic atypia or mitosis were noted. Decidual stromal cells were positive for CD10 and negative for ER. The cytologic diagnosis of endometriosis requires the presence of a biphasic population of cells, glandular epithelial, and stromal cells. But in cases of decidualized endometriosis, the decidualized stromal component is overwhelmingly predominant, and the glandular component is minimal and may be absent. CD10 is a useful immunocytochemical marker for confirming the diagnosis and differentiating it from other tumors common of the abdominal wall in pregnant patients, such as desmoid tumor. Our case demonstrates the usefulness of cytology in diagnosing cutaneous endometriosis. In pregnant patients, fine-needle aspiration diagnosis prevents unnecessary interventional procedures that may jeopardize the pregnancy.

First Report of Fine-Needle Aspiration Cytology on a Pancreatic Solitary Fibrous Tumor

(Poster No. 8)

Vidhya D. Srinivasan, BS1; Jeffrey D. Wayne, MD2; John C. McCallum, BA1 (jmccallum@northwestern.edu); M. Sambasiva Rao, MD1; Debra L. Zynger, MD.1 Departments of 1Pathology and 2Surgery, Northwestern University, Chicago, Ill.

Solitary fibrous tumor (SFT) is an uncommon spindle cell tumor that can occur in a variety of locations. Only 4 prior cases of primary pancreatic SFT have been reported. We report the fifth case in a 78-year-old woman who presented with back pain and 20-lb weight loss. Computerized tomography revealed a 5-cm mass in the body of the pancreas, and an endocrine tumor was considered the likely diagnosis based upon location, vascularity, and well-circumscribed nature. Endoscopic ultrasound with fine-needle aspiration was performed to confirm the radiographic findings, revealing bland-appearing spindle cells positive for CD34 and vimentin, and negative for CAM 5.2, CD117, CD10, chromogranin, synaptophysin, and S100, inconsistent with the radiologic impression. This is the first report of successful cytology on pancreatic SFT. The patient underwent distal pancreatectomy with resection of the mass. Similar to the cytology specimen, the resected tumor was composed of haphazardly arranged bland spindle cells and occasional hemangiopericytoma-like vessels within a background of collagen (Figure 34), and was positive for CD99, Bcl-2, CD34, and vimentin, and negative for smooth muscle actin, CAM 5.2, CD117, CD10, chromogranin, synaptophysin, and S100. Based on histology and immunohistochemistry, a diagnosis of SFT was given. Two months postoperatively, the patient is disease free and has gained 11 lb. Diagnosing pancreatic SFT is challenging due to the rarity, nonspecific clinical presentation, and the difficulty in distinguishing it radiologically from other pancreatic lesions. The expanded use of fine-needle aspiration cytology may be helpful in diagnosing this lesion.

Incidence of Cervical Cytologic Abnormalities Among Women With Inflammatory Bowel Disease When Compared With Healthy Low-Risk Women

(Poster No. 9)

Swarupa Gadre, MD; Santosh K. S. Math, MD (hanan≥farghaly@ yahoo.com); Rania Bakkar, MD; Hanan Farghaly, MD. Department of Pathology, University of Louisville, Louisville, Ky.

Context: Although an increase in cervical cytologic abnormalities has been suggested in patients with inflammatory bowel disease (IBD) compared with healthy low-risk women (HLRW), little has been reported.We evaluated the incidence of cervical cytologic abnormalities among women with IBD when compared with HLRW.

Design: Records were searched for cervical cytology of patients with IBD from 2001 through 2007. Only low-risk women with a biopsy confirmatory of IBD were included in this study. Our search yielded 82 patients, 42 with Crohn disease and 40 with ulcerative colitis. Eighty-two HLRW were matched by age and served as controls. Papanicolaou test diagnoses were categorized as negative for intraepithelial lesion or abnormal, including atypical squamous cells of undetermined significance (ASC-US), low-grade squamous intraepithelial lesion (LGSIL), high-grade squamous intraepithelial lesion, and invasive squamous cell carcinoma.

Results: Eighty-two patients with IBD ranged in age from 19 to 70 years (mean, 42 years), and 82 HLRW ranged in age from 19 to 70 years (mean, 40 years). A total of 8 (9.8%) of 82 patients with IBD had abnormal Papanicolaou tests (2 ASC-US and 6 LGSIL) compared with 6 (7.3%) of 82 HLRW (4 AS-CUS and 2 LGSIL). An interesting finding was that all dysplastic abnormalities seen in patients with IBD were in the patients with Crohn disease (6 LGSIL).

Conclusions: We found a slight statistically significant difference in the number of abnormal cervical cytologies between women with IBD and HLRW. An interesting finding was that the type of IBD may be related to an increased incidence of cervical cytologic abnormalities.

Highly Unusual Malignant Pleural Effusions: Hodgkin Lymphoma, Rhabdomyosarcoma, and Their Look-Alikes

(Poster No. 10)

Fang Qian, MD1; Di Wang, MD2 (wangdi272@yahoo.com); Patricia Tsang, MD.1 1Department of Pathology, Newark Beth Israel Medical Center, Newark, NJ; 2Department of Pathology, Saint Barnabas Medical Center, Livingston, NJ.

Context: Pleural effusion as a first-time presentation of an unusual malignancy can pose a significant diagnostic challenge.

Design: We collected data on all pleural effusions examined at our institution during the past 5 years. All cases reported as malignant were analyzed. Two highly unusual malignant pleural effusions were further evaluated.

Results: Of the 527 patients with pleural effusion, 102 (19%) were diagnosed as malignant. Metastatic adenocarcinoma comprised the vast majority of malignant pleural effusions (89%). Much less common were squamous cell carcinoma, neuroendocrine carcinoma, Hodgkin lymphoma (HL), rhabdomyosarcoma, non-Hodgkin lymphoma, myeloma, and Wilms tumor. In particular, 2 cases, 1 of HL and 1 of rhabdomyosarcoma, posed a significant challenge because of their highly unusual presentation in pleural fluid and the absence of known previous diagnoses. HL was diagnosed on the basis of scattered large tumor cells characteristic of Reed-Sternberg cells (CD15 positive, CD30 positive, PAX-5 positive, CD45 negative, CD20 negative, calretinin negative). The rhabdomyosarcoma revealed single/clusters of malignant cells expressing muscle antigens while lacking epithelial/hematologic markers.

Conclusions: The presence of Reed-Sternberg cells in pleural fluid is exceedingly rare, even though the mediastinum is a frequent site of involvement by nodular sclerosis HL, and benign pleural effusion commonly occurs in HL. It is equally unusual to see rhabdomyosarcoma presenting as pleural effusion, especially in an adult. In the absence of any known prior diagnosis at the time of cytologic review, awareness of rare malignancies in the pleural fluid is crucial for accurate diagnosis. An appropriate panel of immunohistochemical stains performed on the cell block helps to confirm the tumor's cellular origin.

Malignant Melanoma in the Lung: Initial and Unexpected Diagnosis by Fine-Needle Aspiration

(Poster No. 11)

Angela D. Darko, MD (adark001@umaryland.edu); Daniel Dim, MD; Chen-Chih Sun, MD. Department of Pathology, University of Maryland Medical Center, Baltimore.

Primary extracutaneous malignant melanoma is an uncommon entity, although many cases of mucosal-derived (gastrointestinal, respiratory, central nervous system) primary melanoma have been reported. A majority of these cases are thought to be possible metastases from undocumented or regressed primary cutaneous or ocular melanomas. These extracutaneous melanomas have been shown to be biologically more aggressive. Primary malignant melanoma of the lung is a rare neoplasm that may be confused with more conventional types of lung cancer. We report a case of a 59-year-old woman who had a 2-year history ofmultiple quiescent lung nodules with recent enlargement that was consistent with increased burden of disease. She developed an additional 2.3-cm adrenal mass, which had not been previously observed. There was no past history of malignancy or cutaneous lesions. Transbronchial needle aspirationwas performed, and smears were stained with Diff-Quik and Papanicolaou stains. A cell block preparation was also made. The aspirate showed a cellular smear exhibiting singly dispersed as well as small clusters and tight groups of epithelioid cells with abundant cytoplasm. There were scattered binucleated and tumor giant cells. The tumor cells had eccentric nuclei with prominent nucleoli and irregular nuclear membranes. The chromatin pattern was finely granular to hyperchromatic, and numerous intranuclear inclusions were observed. Immunohistochemistry revealed that the tumor cells were positive for S100 and Mart-1 proteins and that rare cells were positive for HMB-45. This case highlights an unusual presentation of pulmonary malignant melanoma in the lung.

Prevalence of Human Papillomavirus Genotypes in a Low-Risk Midwestern US Population

(Poster No. 12)

Bruno A. Schmitz, MD (brunoschmitz551@hotmail.com); Jonathan Henriksen, BS; Noelle Blue Arm, MD; Anthony A. Killeen, MD, PhD; Michelle Dolan, MD; Bharat Thyagarajan, MD, PhD; Stephan Pambuccian, MD; Xijing Wang, MD, PhD. Department of Pathology, University of Minnesota, Minneapolis.

Context: The association of human papillomavirus (HPV) infection and cervical cancer is widely reported in the literature. Little is known, however, about HPV geographic distribution within the United States. It is important to document the distribution of HPV genotypes to predict the potential protection that may be conferred by the currently Food and Drug Administration-approved HPV vaccine (Gardasil).

Design: We detected HPV by polymerase chain reaction (PCR) using MY09/11 primers followed by reflex restriction fragment length polymorphism analysis. We performed this test in patients whose screening Papanicolaou (Pap) test showed ASC-US or whose clinicians requested HPV testing regardless of the screening Pap results. HPV types were tabulated and were correlated with Pap test results and age groups.

Results: From January 2005 to December 2007, we performed 11 006 HPV PCR assays. The corresponding Pap test results for all patients (Surepath) were normal (32.2%), ASC-US (64.8%), ASC-H (1.6%), LSIL (1.2%), HSIL (0.02%), and AGUS (0.1%). The overall HPV positivity rate was 37.1%. HPV type 16 was found in 16.2% of HPV cases and was the most common type detected, followed by HPV types 53 (11.2%), 66 (6.7%), and 6 (6.1%). HPV types 6, 11, 16, and 18 were found in 6.1%, 1.1%, 16.2%, and 4.3%, respectively, of all positive HPV specimens.

Conclusions: This is the first report of HPV genotype prevalence from cervical specimens in the Midwestern United States. This study makes it possible to predict the potential impact of HPV vaccination, but further studies are needed to evaluate the efficacy of vaccination in this population.

Human Papillomavirus Testing of Cervical Cytology in Perimenopausal and Postmenopausal Low-Risk Women: Is It Useful?

(Poster No. 13)

Rania Bakkar, MD (hanan≥farghaly@yahoo.com); Swarupa Gadre, MD; Hanan Farghaly, MD. Department of Pathology, University of Louisville, Louisville, Ky.

Context: Cervical cytology from perimenopausal and postmenopausal women commonly shows squamous cells with nuclear enlargement and slight hyperchromasia that are likely to be interpreted as atypical squamous cells of uncertain significance (ASC-US). Follow-up human papillomavirus (HPV) testing helps to triage patients. Little has been reported on the significance of the detection of HPV DNA in such age groups.

Design: Records were searched for all cervical cytology with ASC-US diagnoses and concurrent HPV DNA test from 2005 through 2007, yielding 158 patients. Only low-risk women with no previous history of abnormal Papanicolaou tests were included in this study. HPV DNA tests were performed on the residual cervical samples of all patients with ASCUS diagnoses. Follow-up Papanicolaou tests diagnoses were categorized as negative for intraepithelial lesion (NIL) or abnormal, including atypical squamous cells (ASC-US/ASC-H), low-grade squamous intraepithelial lesion (LGSIL), high-grade squamous intraepithelial lesion, and invasive squamous cell carcinoma based on 2 age groups: group A (40-49 years) and group B (≥50 years).

Results: Within group A, 39 patients were diagnosed with ASC-US, 9 of 39 were HPV DNA positive, and 3 patients had follow-up by cytology (1 NIL and 2 LGSIL). Within group B, 48 patients were diagnosed with ASC-US, 8 of 48 were HPV DNA positive, and 3 patients had follow-up by cytology (2 NIL and 1 ASC-H).

Conclusions: A diagnosis of ASC-US in perimenopausal and postmenopausal women is likely to result in a negative HPV DNA test. The detection of dysplasia was significantly lower in postmenopausal women than that in perimenopausal women.

Concomitant Immunostaining of Individual Cervical Cells for p16 and Ki-67 as an Indicator of Cell Cycle Dysregulation and Dysplasia

(Poster No. 14)

Ruediger Ridder, PhD1 (ridder@mtmlabs.com); Marcus J. Trunk, MD1; Petra Klement, PhD1; K. Ulrich Petry, MD2; Dietmar Schmidt, MD.3 1Department of Research & Development, mtm laboratories, Heidelberg, Germany; 2Department of Gynecology and Obstetrics, Klinikum der Stadt Wolfsburg, Germany; 3Department of Gynecopathology, Institute of Pathology, Mannheim, Germany.

Context: Overexpression of p16 in cells with intact cell cycle regulation results in cell cycle arrest. In contrast, p16 has been shown to be strongly overexpressed in cervical dysplastic cells that have undergone HR-human papillomavirus-mediated cell cycle dysregulation. Coexpression of antiproliferative (p16) and proliferation markers should exclude each other in cells with intact cell cycle regulation. The detection of cells immunoreactive for both p16 and Ki-67 in cervical cytology specimens may therefore indicate presence of cervical dysplasia.

Design: Eight hundred twenty-one cervical cytology specimens from a screening population and 161 cytology specimens sampled from women attending a dysplasia clinic and having biopsy follow-up were analyzed using a p16/Ki-67 dual immunocytochemical staining protocol.

Results: Six (<1%) of 620 Papanicolaou-negative, human papillomavirus-negative cases showed any cervical cell expressing both p16 and Ki-67 within the same cell. In addition, 55 of 201 cytology cases initially called normal on Papanicolaou cytology and that tested positive for HRhuman papillomavirus presented p16/Ki-67 double-immunoreactive cells. Almost all of these cases with double-immunoreactive cells showed cervical cells with equivocal or mildly abnormal morphology upon second review of the Papanicolaou slides. For a separately assessed group of 161 cytology specimens sampled during a colposcopy visit, calculated sensitivity for biopsy-confirmed CIN 2+ of positive double-stain test results obtained on these cytology specimens was 91%.

Conclusions: Detection of individual cells immunoreactive for both p16 and Ki-67 in cervical cytology specimens represents a promising novel approach with the potential to provide a tool widely independent from morphology interpretation and with both high specificity and sensitivity for cervical dysplasia.

Financial Disclosures: Dr Ridder owns stock in mtm laboratories. Dr Petry is a consultant to mtm laboratories.

The Diagnostic Dilemma of Daisy Cells

(Poster No. 15)

Stephen Samuel, MD (ssamuel@swmail.sw.org); Jared Szymanski, DO; V. O. Speights, DO. Department of Pathology, Scott and White Memorial Hospital and Texas A&M Health Science Center College ofMedicine, Temple.

The diagnosis of a mesothelial malignancy from a fluid sample is often problematic because mesothelial cells can appear in various forms and can occasionally mimic malignancy. We present a case of peritonealwashings obtained from a 67-year-old man for staging of malignant pleural mesothelioma that contained atypical cells that were initially worrisome for metastasis. Staging procedures, including bronchoscopy, mediastinoscopy, and peritoneal biopsy, were all negative for metastatic disease.However, the peritoneal washings submitted for cytologic evaluation contained several atypical cells in a background of normal mesothelial cells. The most alarming feature of these atypical cells was the presence of lobulated, floret-shaped normochromatic nuclei (Figure 35). These florets were primarily arranged in sheets and clusters. A few of these unusual cells had nucleoli. Given the presence of a pleural malignancy, these atypical cells were worrisome for metastasis. However, after some consideration and a review of the literature on the subject, a consensus was reached that these cells were Daisy cells. They are rare, reactive, peritoneal mesothelial cells which were first described by McGowan and Davis in 1970. To our knowledge, this is the first reported case of Daisy cells in a man. This case illustrates the diagnostic dilemma one often faces when assessing body fluids for mesothelial malignancy. Although mesothelial cells may appear atypical and peculiar, they may not necessarily be malignant. A careful examination and, on occasion, a literature review, may help clarify the nature of the diagnosis.

The Role of Computed Tomography-Guided Fine-Needle Aspiration of Lung Mass-Forming Lesions at a Large Teaching Hospital

(Poster No. 16)

Daniel W. Davis, DO (dwdavis2465737@yahoo.com); Jing Liu, MD, PhD. Department of Pathology and Laboratory Medicine, University of Texas, Houston.

Context: Fine-needle aspiration (FNA) has become a favored diagnostic method for evaluating mass-forming lung lesions.

Design: We reviewed 120 archival cases of lung FNA during a 3-year period. FNAs were performed under computed tomography guidance and with immediate pathologic assessment for specimen adequacy. The patients included 66 males and 54 females with a mean age of 62.5 years (range, 11-92 years). Based on diagnosis, cases were divided into 1 of 5 categories: inadequate, benign, atypical (probably benign), atypical (suspicious for malignancy), and malignant.

Results: Of the 120 cases, 69 (57.5%) were positive for malignancy, 34 (28.3%) were benign, 2 (1.7%) were atypical (probably benign), 5 (4.2%) were atypical (suspicious for malignancy), and 10 (8.3%) were inadequate. The malignant neoplasms included 61 (50.8%) primary lung carcinomas (31 adenocarcinomas, 8 squamous carcinomas, 16 non-small cell carcinomas-not otherwise specified, 5 small cell carcinomas, and 1 basaloid carcinoma) and 8 (6.7%) metastatic tumors to the lung. Of the 34 benign lesions, 26 (21.7%) were classified as nonspecific inflammatory/reactive conditions, 3 (2.5%) showed acid-fast bacilli, 4 (3.3%) showed fungal organisms, and 1 (0.8%) was a hamartoma.

Conclusions: Computed tomography-guided FNA was an invaluable diagnostic tool for pulmonary mass-forming lesions, yielding a definitive diagnosis in 77 (64.2%) of 120 cases. The unsatisfactory rate was low (8.3%). The FNA evaluation for the remaining 33 cases (27.5%) provided cytologic information for further workup and clinical management. Pathology residents were adequately exposed to a variety of lung FNA cases. The computed tomography-guided lung FNA has adequately served this large teaching hospital.

Cytologic Diagnosis of Pancreatic Adenocarcinoma With or Without Immunocytochemical Staining for S100P and von Hippel-Lindau Gene Product

(Poster No. 17)

Jing Liu, MD, PhD1 (Jing.Liu.1@uth.tmc.edu); Uma Kundu,MD1; Susan Zacharizh, BS2; Robert E. Brown, MD.1 1Department of Pathology and Laboratory Medicine, University of Texas at Houston Medical School, Houston; 2Cytology Laboratory, Memorial Hermann Hospital, Houston, Tex.

Context: Fine-needle aspiration (FNA) is the method of choice used preoperatively for the diagnosis of pancreatic adenocarcinoma. Accurate morphologic distinction between pancreatic adenocarcinoma and benign pancreatic ductal cells can be challenging in cytologic specimens. Immunostaining for S100P and von Hippel-Lindau gene product (pVHL) on histologic sections has demonstrated that these markers are useful in distinguishing pancreatic adenocarcinoma from its benign counterpart.

Design: We reviewed 12 pancreatic FNA specimens with cell blocks from 12 patients with pancreatic adenocarcinoma that was subsequently confirmed by histologic findings and/or clinical correlation. In this retrospective study, immunostains with S100P and pVHL antibodies were applied to unstained recuts from cell blocks. Nuclear or nuclear/cytoplasmic staining was defined as positive immunoreactivity for S100P. Membranous/cytoplasmic staining was considered to be immunopositive for pVHL.

Results: Original FNA diagnoses without immunostaining for S100P and pVHL were adenocarcinoma for 9 cases and atypical cytologic change/suspicious for adenocarcinoma for 3 cases due to scant cellularity. On immunostained cell block sections, the tumor cells in all (12/12) pancreatic adenocarcinomas were positive for S100P and negative for pVHL, including the 3 cases with an original atypical/suspicious cytologic diagnosis. We feel that these 3 cases, in light of the immunostaining results, should be reclassified as adenocarcinoma.

Conclusions: The results of this study show that S100P and pVHL antibodies can be used as an immunostaining panel to facilitate cytologic diagnosis of pancreatic adenocarcinoma. The diagnostic accuracy and confidence level are increased by finding immunopositivity for S100P and immunonegativity for pVHL.

Evaluation of ThinPrep UroCyte Slide Preparation for Gastrointestinal Cytology Specimens

(Poster No. 18)

Barbara Chadwick, MD1 (barbara.chadwick@hsc.utah.edu); G. Denice Smith, PhD, CT(ASCP)2; Joel Bentz, MD.1,2 1Department of Pathology, University of Utah, Salt Lake City; 2ARUP Institute for Clinical and Experimental Pathology, Salt Lake City, Utah.

Context: Gastrointestinal tract cytology using standard slide preparations is known to have high specificity but poor sensitivity for detecting gastrointestinal tract malignancy. Newer methods of slide preparation may permit coupling of cytology with molecular slide-based assays that could improve diagnostic sensitivity.

Design: Slides prepared by a liquid-based cytology using ThinPrep filters (Non-GYN and UroCyte, Cytyc Corporation, Marlborough, Mass) were compared by split-sample validation study to compare cellularity, stain quality, and interpretation of slides prepared with the standard method (cytocentrifugation). We compared cytologic/histologic outcomes for 1-year periods before and after implementation. Of the 277 cases, 42% had follow-up. Sixty-five historical cohort cases and 52 concurrent cases were included for review.

Results: UroCyte slides were noted to be superior to the ThinPrepNon-GYN filter and standard preparations, showing improved cellularity and stain quality. Cytologic diagnoses were categorized as negative, atypical, atypical-suspicious for malignancy, or malignant. Statistics were calculated with inclusion and exclusion of atypical categories (Figure 36). Sensitivity, specificity, positive predictive value, and negative predictive value were similar in both groups.

Conclusions: The use of UroCyte for exfoliative gastrointestinal cytology specimens allows for improved slide evaluation and approximately equivalent diagnostic outcomes versus standard preparations. Importantly, this methodology allows for ease of evaluation by molecular methods, such as fluorescence in situ hybridization, particularly for esophageal and bile duct brushings. We conclude that use of UroCyte filters for evaluation of gastrointestinal cytology specimens is a valid preparation and simplifies the addition of adjunct molecular testing.

Histiocytoid Carcinoma of the Male Breast

(Poster No. 19)

C. B. Hutchinson, MD (blake.hutchinson@duke.edu); Joseph Geradts, MD. Department of Pathology, Duke University Medical Center, Durham, NC.

Histiocytoid carcinoma of the breast is a rare tumor, with approximately 30 cases reported and with all of those occurring in females. We report a 68-year-old man who presented with a 2.5-cm breast mass. Microscopic examination of the needle core biopsy revealed a proliferation of neoplastic cells infiltrating the stroma as angulated clusters, linear arrangements, small nests, and individually; there was no tubule formation. The nuclei were round to oval, hyperchromatic, and demonstrated inconspicuous nucleoli and finely dispersed chromatin. The cytoplasm was abundant, amphophilic, and ranged from granular to vacuolated. A subset of tumor cells contained periodic acid-Schiff-positive cytoplasmic material, which was largely but incompletely removed by diastase treatment. There was minimal nuclear pleomorphism, and mitotic figures were inconspicuous. The intervening stroma was densely fibrotic, and the tumor infiltrated among tightly packed collagen bundles. Immunohistochemistry was positive for estrogen receptor, progesterone receptor, androgen receptor, vimentin, epithelial membrane antigen, and pancytokeratin. The tumor was negative for CK7, CAM5.2, 34βE12, AE1/AE3, GCDFP-15 (BRST-2), E-cadherin, and CD68. The mastectomy demonstrated a single circumscribed mass with similar histologic findings. Sentinel lymph node biopsy was negative. The morphology and staining characteristics of this tumor were similar to those described for histiocytoid carcinoma of the female breast, a rare entity. Such tumors are felt to be variants of lobular carcinomas; this belief is supported by diffuse infiltrative growth, loss of E-cadherin expression, and strong estrogen receptor positivity.We believe our case to be the first reported example of histiocytoid carcinoma in a male breast.

Acinic Cell Carcinoma of the Breast With Sarcomatoid Features: A Case Report and Review of the Literature

(Poster No. 20)

Sarah M. Bean, MD (sarah.bean@duke.edu); John A. Papalas, MD; Rex Bentley, MD; Joseph Geradts, MD; Jim Burchette, MTSP. Department of Pathology, Duke University Medical Center, Durham, NC.

Acinic cell carcinoma of the breast (ACCB) is rare; only 11 cases have been reported in the English literature. None of the reported tumors had metaplastic/sarcomatoid components. We describe the clinicopathologic, immunohistochemical, and ultrastructural characteristics of ACCB with sarcomatoid features and review the literature. Tissues were processed using standard histologic, immunohistochemical, and electronmicroscopic protocols. Use of human tissue was approved by the Duke University Medical Center Institutional Review Board. A 2.5-cm, well-circumscribed tumor was histologically multiphasic. Areas of acinar-like glands, focal sarcomatoid differentiation, atypical microglandular proliferation, and high-grade invasive ductal adenocarcinoma were all identified. The acinar component had glandular structures lined by columnar cells with basally oriented nuclei and eosinophilic, granular cytoplasm. Electronmicroscopy demonstrated abundant mitochondria and numerous cytoplasmic vesicles (0.5 to 1.1 µm). Histochemical, immunoperoxidase, and hormone receptor studies were performed (Table). The patient is currently disease free 18 months after diagnosis and 12 months after resection. ACCB is a rare tumor characterized by acinar-like growth with a reported good prognosis. Tumors are reactive with amalyse, lysozyme, and epithelial membrane antigen and are estrogen receptor/progesterone receptor/HER2-neu negative. Electron microscopy shows exocrine type differentiation. More than one fourth of ACCB cases to date have been misdiagnosed as either atypical microglandular adenosis or carcinoma arising within a microglandular lesion. Prognosis is generally good.

Benign Ectopic Breast Tissue in the Medulla of an Axillary Sentinel Lymph Node

(Poster No. 21)

Debra L. Zynger, MD (d-zynger@md.northwestern.edu); John C. McCallum, BA; Michael J. Everton, MD; Barbara Susnik, MD, PhD; Anjana V. Yeldandi, MD. Department of Pathology, Northwestern University, Chicago, Ill.

Benign glandular inclusions in axillary lymph nodes are uncommon, and their presence in axillary sentinel lymph nodes (SLN) is exceptionally rare. The possibility of overstaging due to misinterpretation of benign glandular inclusions is a concerning issue. We present a 54-year-old woman with high-grade ductal carcinoma in situ undergoing simple mastectomy with SLN biopsy. Frozen section of the 1.7-cm SLN was unremarkable. No invasion was identified in the mastectomy specimen. Permanent sections of the SLN were made (Figure 37). The most superficial level (level 1) revealed 14 scattered naked small glands in the medulla with no surrounding stroma. The glandular area in the deepest level (level 3) was much larger (2 mm) and was well circumscribed, with packed cytologically bland glands separated by stroma. A myoepithelial layer was visible in most glands in the deepest level, which was confirmed by calponin, smooth muscle myosin heavy chain, CD10, and p63 immunohistochemistry (Figure). A final diagnosis of benign ectopic breast tissue within an axillary SLN was rendered. Previous studies have identified axillary SLN in which benign glandular inclusions were separated by stroma or were subcapsular in location. It has been suggested that medullary location and absence of stroma are characteristics of malignantmetastatic glands.However, this case demonstrates that medullary location and lack of surrounding stroma (as seen in superficial levels) are not reliable features of malignancy. We recommend that benign glandular inclusions should be a diagnostic consideration for medullary located naked glands that do not histologically resemble the corresponding primary tumor.

Differential Gene Expression: Profiling of Carcinoma-Associated Fibroblasts in Invasive Breast Cancer

(Poster No. 22)

Rong He, MD (rhe@uwhealth.org); Gui Su, PhD; William Rehrauer, PhD; Michelle Waknitz, BS; Maret Bauer, MD; Andreas Friedl, MD. Department of Pathology, University of Wisconsin Hospital and Clinics, Madison.

Context: Breast carcinoma is the most common cancer in women. It is characterized by epithelial malignant transformation followed by stromal invasion and is commonly associated with desmoplasia. Carcinoma-associated fibroblasts (CAF) support and promote epithelial tumorigenesis. Novel gene products expressed in CAF could serve as biomarkers for early detection of invasive carcinoma or as therapeutic targets. We investigated the differential gene expression profile of CAF versus normal fibroblasts in invasive breast cancer.

Design: Paired CAF and normal fibroblasts were isolated from 6 breast carcinoma samples and adjacent normal tissue (confirmed by histology). RNA was extracted from primary cultures of CAF and normal fibroblasts, reverse transcribed, labeled, and hybridized to a Human Genome U133 Plus 2.0 Array (Affymetrix, Santa Clara, Calif). The data were studied using empirical Bayes method, and gene lists indicating differential expression were generated (posterior probability of equivalent expression, <0.01; fold change, 2; sorted by q value). Ten genes with significant fold changes and biologic relevance were validated by real-time quantitative reverse transcription-polymerase chain reaction.

Results: Among the 47 000 analyzable transcripts, 31 genes were upregulated in CAF. Known gene classes in this group include signal transduction molecules, growth factors/cytokines, and extracellular matrix proteins. Thirteen genes were downregulated in CAF. Reverse transcription-polymerase chain reaction analysis of 10 lead genes confirmed the validity of the differential gene expression pattern revealed by microarray analysis.

Conclusions: In invasive breast cancer, CAF demonstrate distinct gene expression patterns when compared with normal fibroblasts. These expression signatures could serve as candidate biomarkers for invasive breast cancer and/or potential therapeutics targets.

Lack of Cytoplasmic Expression of Xanthine Oxidoreductase in Invasive Male Breast Carcinoma Is Associated With a Higher Number of Positive Axillary Lymph Nodes

(Poster No. 23)

Allison T. Howard, MD1 (allison≥howard@rush.edu); Vijaya Reddy, MD1; Linda Green, MD2; Kalliopi Siziopikou, MD, PhD1; Pincas Bitterman, MD1; Richard Prinz, MD3; Xiulong Xu, PhD3; Paolo Gattuso, MD.1 Departments of 1Pathology and 3General Surgery, Rush University Medical Center, Chicago, Ill; 2Department of Pathology, Baylor College ofMedicine, Houston, Tex.

Context: Xanthine oxidoreductase (XOR) is an enzyme expressed in normal breast epithelium. Although data are limited, decreased cytoplasmic expression of XOR has been associated with several adverse prognostic features in female breast carcinoma patients. We retrospectively studied XOR expression in relation to axillary lymph node status and size of the tumor in male breast carcinoma patients.

Design: Fifty-three cases of invasive male breast carcinoma were immunostained for XOR using standard avidid-biotin technique. For each case, the percentage of tumor cells staining was scored as positive if 10% or more of cells had cytoplasmic staining. XOR expression was analyzed in relation to lymph node status and tumor size by Fisher exact χ^sup 2^ test.

Results: Thirty-five cases were T1 lesions, and 18 cases were T2 lesions. Twenty-five had positive lymph nodes; 28 had negative lymph nodes. Overall, 30 cases (56.6%) expressed XOR. XOR was expressed in 9 (36%) of 25 positive lymph nodes and in 21 (75%) of 28 negative lymph nodes (P = .006). XOR was expressed in 19 (54.3%) of 35 T1 lesions and in 10 (55.5%) of 18 T2 lesions (P = not significant).

Conclusions: Lack of cytoplasmic XOR expression in invasive male breast carcinoma is associated with increased risk of lymph node metastasis. However, there was no correlation present between the tumor size and lack of XOR expression. Why XOR is lost in the more aggressive form of invasive male breast carcinoma remains unknown. Further studies are needed to elucidate whether tumors lacking XOR expression respond differently to adjuvant therapy than those expressing XOR.

Pleomorphic Lobular Carcinoma In Situ in Core Biopsy: Clinicopathologic Characterization and the Need for Subsequent Excision

(Poster No. 24)

Sihem Khelifa, MD (s-khelifa@northwestern.edu); Yurdanur Sullu, MD; Barbara Susnik, MD, PhD. Department of Pathology, Nothwestern University, Chicago, Ill.

Context: Lobular carcinoma in situ encompasses a heterogeneous group of lesions associated with risk of subsequent breast carcinoma. The pleomorphic type may also have a capacity to progress to invasive lobular carcinoma and needs further characterization.

Design: Fifteen cases of pleomorphic lobular carcinoma in situ (PLCIS) diagnosed in core biopsy (CB) from January 2006 to January 2008 were retrieved from files. Diagnostic criteria required at least moderate nuclear pleomorphism, nuclear size ≥4 times the small lymphocyte, and negative E-cadherin staining. Morphology and clinical characteristics were reviewed in CB and subsequent surgical specimens (available in 13/15 cases).

Results: Patient age ranged from 41 to 78 years (mean, 55.4 years). Cases presented as suspicious calcifications (n = 11), mass (n = 2), or both (n = 2). Six patients (40%) had family history; 5 patients (33%) had personal history of breast carcinoma (2 contralateral). PLCIS involved 15% to 100% of lobules in the CB specimens (mean, 70%), with marked distention of ductules in 11 (73%) of 15, necrosis in 9 (60%) of 15, and associated microcalcifications in 10 (67%) of 15 cases. PLCIS was estrogen receptor negative in 2 of 14 and HER-2 positive in 3 of 12 cases. PLCIS was associated with invasive lobular carcinoma in 6 (40%) of 15 cases, with 4 in CB and 2 in surgical specimens (mean size, 0.2 cm; range, κ0.1-0.6 cm). One case had metastatic carcinoma (T1micN1).

Conclusions: PLCIS in CB is diagnosed in postmenopausal women with suspicious calcifications who often have a personal or family history of breast carcinoma. Its common association with invasive lobular carcinoma indicates its aggressive nature and warrants surgical excision.

β-Human Chorionic Gonadotropin Production Associated With Phyllodes Tumor of the Breast: An Unusual Paraneoplastic Phenomenon

(Poster No. 25)

Emily S. Reisenbichler, MD1 (esreisen@uab.edu); Helen Krontiras, MD2; Omar Hameed, MBChB.1 Departments of 1Pathology and 2Surgery, University of Alabama School of Medicine, Birmingham.

Phyllodes tumors (PTs) of the breast are uncommon and account for less than 1% of all breast tumors. Most patients present with mass lesions; however, there are rare reports of patients presenting with paraneoplastic conditions, such as hypoglycemia secondary to insulin-like growth factor II secretion. A 55-year-old woman presented with a rapidly enlarging left breast mass that ulcerated through the skin and invaded the underlying chest muscle. The serum β-human chorionic gonadotropin (hCG) level was found to be 58 mIU/mL preoperatively; this dropped to 2 mIU/mL after surgery. Mastectomy showed a 14.5-cm fibroepithelial neoplasm, the majority of which was composed of a cellular spindle/epithelioid cell stroma with the focal presence of elongated epithelial clefts consistent with a PT (Figure 38). In addition to the presence of unequivocal sarcomatous stromal overgrowth and prominent mitotic activity ( 10 per 10 high-power fields), there were areas of lacelike osteoid production by tumor cells. A diagnosis of malignant PT with osteosarcomatous foci was rendered. Immunohistochemical studies showed focal β-hCG expression within the epithelioid stroma of the tumor; expression of p63 and cytokeratin was only seen in the epithelial component, and there was no expression of placental alkaline phosphatase in either component. Although β-hCG expression/production has been described in many nontrophoblastic tumors (mostly carcinomas of various organs), to our knowledge this is the first case documenting this in a PT of the breast. Whether this intriguing finding represents an isolated association or has more significant implications remains to be determined.

Biopsy Correlation of American College of Radiology Breast Imaging Reporting and Data System Category 4 Mammographic Calcifications: Does the Pattern of Calcification Predict Likelihood of Malignancy?

(Poster No. 26)

Cassie L. Boggs, MD1 (drdead2011@gmail.com); Fernanda Kraemer, MD2; H. Davis Massey, MD1; Margaret M. Grimes, MD1; Gilda Cardenosa, MD2; Michael O. Idowu, MD.1 Departments of 1Pathology and 2Radiology, Virginia Commonwealth University, Richmond.

Context: American College of Radiology Breast Imaging Reporting and Data System (BIRADS) category 4 calcifications are defined as suspicious for malignancy, necessitating a biopsy. However, BIRADS 4 calcifications are heterogeneous, and fewer than half of the corresponding biopsies show a malignancy. We reviewed the pathologic findings in BIRADS 4 calcifications at our institution to identify the patterns of calcifications that were most often associated with malignancy.

Design: Our surgical pathology records were searched for core-needle breast biopsies performed for BIRADS category 4 calcifications during a 2-year period. Only cases with calcifications, with or without associated masses or distortion, were included in the study. Biopsies performed only for mass or distortion without calcifications were excluded. Biopsies performed for calcifications other than BIRADS 4 pattern per radiology report were also excluded. The biopsy findings were correlated with the descriptions of the mammographic calcifications. All cases were discussed with the radiologist to determine correlation.

Results: A total of 523 biopsies were performed during the 2-year period. Of these, 129 cases (24.7%) were performed for category 4 calcifications with or without mass/distortion. Calcifications were identified on histologic examination in all cases. The calcifications most commonly associated with malignancy are linear with linear pattern (71%), pleomorphic (71%), and those associated with a mass or parenchymal distortion (75%; Table).

Conclusions: While all BIRADS 4 calcifications patterns may be associated with breast malignancies, pleomorphic, linear with linear pattern, and calcifications associated with a mass or parenchymal distortion are more commonly associated with breast malignancies. Radiologic-pathologic correlation in all cases is essential.

The Expression of Cyclin D1 and BCL-2 in Estrogen-Negative and Triple-Negative Invasive Mammary Carcinoma

(Poster No. 27)

Regina S. Burton, MD; Cassie L. Boggs, MD (drdead2011@gmail. com); Travis Mullan, HT; Michael O. Idowu, MD. Department of Pathology, Virginia Commonwealth University, Richmond.

Context: There is an increased interest in the role that BCL-2 and cyclin D1 play in the estrogen-positive breast cancer resistance to tamoxifen. The purpose of the study was to evaluate the expression of BCL-2 and cyclin D1 in reference to estrogen receptor status, triple negativity (estrogen receptor negative, progesterone receptor negative, and HER-2 negative) and tumor recurrence.

Design: Sixty-four archived surgical pathology cases were reviewed. Thirty-seven (57.8%) of 64 cases were estrogen receptor positive, whereas 27 cases (42.2%) were estrogen receptor negative. Twenty-two (34.4%) of 64 cases were triple negative. Twelve (18.8%) of 64 cases had subsequent recurrence. Representative slides from all cases were evaluated with BCL-2 and cyclin D1 by immunohistochemistry. The cases were evaluated with regard to intensity (0-3+) and percentage of tumor cells staining (0%-100%). Only cases that had intensity of 2+ with greater than 5% staining were regarded as positive. χ^sup 2^ was used to evaluate the significance of the staining pattern.

Results: Thirty-three (51.6%) of 64 cases were cyclin D1 positive, and of these, 25 (75.8%) were estrogen receptor positive (Table). Of the 12 recurrent cases, 9 (75%) were triple negative, and 4 of these were positive for both BCL-2 and cyclin D1.

Conclusions: BCL-2 and cyclin D1 appear to be differentially expressed in estrogen-positive tumors. BCL-2 is significantly more expressed in non-triple-negative tumors. BCL-2 and cyclin D1 expression may be related to hormone receptor status and may not be independently prognostic.

Matrix-Producing Breast Carcinoma: A Rare and Potentially Misrecognized Breast Carcinoma Variant

(Poster No. 28)

Claudine A. Morcos, MD (morcos@gwu.edu); Robert V. Jones, MD; Jan M. Orenstein, PhD; Michael D. Stamatakos, MD. Department of Pathology, The George Washington University Medical Center,Washington, DC.

Metaplastic breast carcinomas are rare (0.3%-5% of all breast cancers) neoplasms characterized by a variable admixture of adenocarcinoma with nonepithelial cellular and stromal elements. Matrix-producing carcinoma (MPC) is a microscopically distinct variant of metaplastic breast carcinoma that consists of carcinoma with direct transition of carcinomatous epithelium to matrix-forming cells that elaborate abundant chondroid and/or osseous stromal matrix. We reviewed the breast core biopsy and subsequent surgical resection specimen from a 78-year-old woman who presented with a palpable breast mass. The core biopsy demonstrated a highgrade invasive ductal carcinoma with extracellular mucin production and necrosis (Figure 39). The resection specimen showed nests and cords of neoplastic cells, which stained with cytokeratin AE1/AE3, epithelial membrane antigen, and S100, embedded in a blue-graymucoid-appearing matrix. Complete sampling of the resection specimen conclusively demonstrated that the blue-gray background mucoid material actually represented the chondromyxoid matrix of an MPC. Transmission electron microscopy revealed a glandular component, with the stroma containing electron-dense matrix material and proteoglycans, that was consistent with MPC. MPC may be difficult to distinguish from invasive mucinous carcinoma on a needle-core biopsy. MPC should be considered in the differential diagnosis of invasive breast carcinomas with extracellularmucin production. The presence of nests and cords of cells as opposed to free-floating islands of tumor cells, and the presence of high-grade cytologic atypia, favor the diagnosis of MPC over invasive mucinous carcinoma. The distinction is clinically important because, unlike invasive mucinous carcinoma, MPC is an aggressive form of invasive breast carcinoma.

CD44-Positive and CD24-Negative Stem Cells and CD44 Are Differentially Expressed in Estrogen-Negative and High-Grade Invasive Mammary Carcinoma

(Poster No. 29)

Regina S. Burton, MD; Cassie L. Boggs, MD (drdead2011@gmail. com); Travis Mullan, HT; Michael O. Idowu, MD. Department of Pathology, Virginia Commonwealth University, Richmond.

Context: Breast cancer stem cells defined as CD44 (positive)/CD24 (negative/low) are thought to be slowly cycling cells; thus, they may escape intervention targeted at proliferating cells, resulting in failures/recurrences. The purpose of this study was to evaluate the expression of CD44 and stem cells in tumors with regard to estrogen receptor (ER) status, tumor grade, and recurrence.

Design: Sixty-four archival tissues were identified. Of these, 27 (42%) were ER negative, 31 (48.4%) were high grade (grade 3), and 12 showed recurrence. CD44 and CD24 immunohistochemical stains were performed on all specimens. The intensity (0-3+) and percentage (0%-100%) of tumor cells stained were evaluated. 2+ intensity with at least 5% of cells stained was considered positive. χ^sup 2^ was used for statistical evaluation.

Results: Of the 12 cases with recurrent carcinoma, 9 (75%) were estrogen negative. Of these 9, 7 (77.8%) were CD44 positive and 6 (66.7%) had stem cells. Twenty-three (74.2%) of 31 high-grade cases and 13 (39.4%) of 33 low-grade cases were CD44 positive (P = .005). Ten (43.5%) of 23 high-grade cases and 7 (25%) of 28 low-grade cases had stem cells (P < .001). Of the 21 cases that were CD44 positive and ER negative, 18 were grade 3. Of the 12 cases that were CD44 positive and ER positive, 2 were grade 3 (Table).

Conclusions: CD44 and stem cell expression in mammary carcinoma may not be an independent prognostic factor, but expression may be related to the ER status and histologic grade of the tumor cells.

Significance of Microinvasive Carcinoma in Breast Core Biopsy

(Poster No. 30)

Sihem Khelifa, MD (s-khelifa@northwestern.edu); Yurdanur Sullu, MD; Barbara Susnik, MD, PhD. Department of Pathology, Nothwestern University, Chicago, Ill.

Context: The significance of microinvasive carcinoma (MI) in breast core biopsy is not well defined.

Design: Thirty-three breast core biopsy specimens with MI were retrieved from files (January 2006-January 2008). Inclusion criteria required foci suspicious (n = 3) or definite (n = 30) for microinvasion (<0.1 cm). Morphology and clinical characteristics were reviewed in core biopsy specimens and subsequent surgical specimen, which was available in 31 of 33 cases.

Results: Patient age ranged from 32 to 82 years (mean, 56.7 years). In 8 patients (24%), there was a history of contralateral breast carcinoma, and 9 patients (27%) had a family history of breast carcinoma. Cases presented as suspicious calcifications (n = 22), mass (n = 6), or both (n = 5). MI was unifocal in 75% of cases, with a pattern of isolated cells (45%), small nests (24%), or tubules/glands (18%). MI had nuclear grade 3 (58%), 2 (36%), or 1 (6%). All MIs were associated with carcinoma in situ, ductal (91%) or lobular (9%) type. Associated carcinoma in situ was commonly grade 3 (73%), nodule/mass forming (39%), associated with marked fibrosis (45%) and lymphocytic reaction (42%), estrogen receptor positive (60%), and HER-2 negative (70%). Surgical specimens showed upstaging of MI to invasive carcinoma in 29% (mean size, 0.6 cm), remaining MI in 26%, and carcinoma in situ in 45% of cases. Two of 31 cases with sentinel lymph node biopsy had metastatic carcinoma (T1aN1).

Conclusions: MI is a rare finding in CB and is upstaged to invasive carcinoma in one third of surgical specimens. Clinicopathologic review did not identify any feature that was predictive of upstaging.

Foiled Again: Local Experience Does Not Support Previously Described Specificity in Cytokeratin AE1/AE3 Staining of Breast Cancer Sentinel Lymph Nodes

(Poster No. 31)

Julie W. Lemmon, MD (julie.lemmon@us.army.mil); James F. Shikle, MD. Department of Pathology, Dwight D. Eisenhower Army Medical Center, Fort Gordon, Ga.

Context: When performing immunohistochemical stains on lymph nodes to detect micrometastatic breast carcinoma, plasma cells can stain positively with pancytokeratin markers. Current literature indicates that CAM 5.2 is predominantly subject to this phenomenon and advocates the use of AE1/AE3 to avoid potential false-positive interpretation. In our experience, plasma cells in sentinel lymph nodes can be immunoreactive to cytokeratin AE1/AE3.

Design: Ten cases of breast cancer with sentinel lymph node biopsies were reviewed. Among the 10 cases were a total of 27 lymph nodes designated as sentinel. Each lymph node was examined for the presence of plasma cell staining. The commercial laboratory that performed each immunohistochemical stain and the vendor for the AE1/AE3 reagents were noted.

Results: Of the 27 lymph nodes examined, all were stained at 1 of 2 commercial laboratories using an AE1/AE3 keratin cocktail. Ten lymph nodes from 5 patients were processed with Ventana (Tucson, Ariz) reagents, whereas 17 lymph nodes (from 5 patients) were processed with Zymed (Carlsbad, Calif) reagents. Plasma cell staining was noted in 7 of 27 lymph nodes.

Conclusions: In this limited retrospective review, we document that plasma cells are subject to aberrant staining with cytokeratin AE1/AE3. Cell distribution and staining quality remain important factors in the interpretation of immunohistochemical studies of breast cancer sentinel lymph nodes. Absolute immunohistochemical specificity continues to remain elusive.

Mammaglobin and Estrogen Receptor Cocktail: A Novel Diagnostic Tool for Identifying Metastatic Breast Carcinoma

(Poster No. 32)

Zhiqiang Wang, MD, PhD1 (zwang@tmhs.org); Jae R. Ro, MD, PhD1; Gyung Y. Gong, MD2; Candice Hamilton, BS1; Mary R. Schwartz, MD1; Jim Zhai, MD.1 1Department of Pathology, The Methodist Hospital, Houston, Tex; 2Department of Pathology, Asan Medical Center, Ulsan University School of Medicine, Seoul, Republic of Korea.

Context: Current ancillary tests to identify occult metastatic breast carcinoma are suboptimal in terms of sensitivity and specificity. We evaluated a cocktail composed of mammaglobin and estrogen receptor (ER) in a cohort composed of primary breast invasive ductal carcinoma and their paired metastases to ipsilateral axillary lymph nodes.

Design: Grading was based on modified Elston Scarff-Bloom-Richardson criteria. Eighty paraffin-embedded tissue sections were immunostained using a mouse monoclonal antibody raised against human mammaglobin (clone 304-1A5, Dako, Carpinteria, Calif; 1:100) and ER (clone 6F11, Novocastra, Newcastle upon Tyne, United Kingdom; 1:50). These sections consisted of 40 primary breast invasive ductal carcinomas and 40 metastases to ipsilateral axillary lymph nodes. Immunostaining intensity was graded as 1+ (weak), 2+ (moderate), and 3+ (strong); the staining proportion was recorded as percentage of tumor area. Staining with 2+ and 10% was defined as being positive.

Results: There were 7 grade 1, 28 grade 2, and 5 grade 3 tumors. Cytoplasmic mammaglobin staining and ER nuclear staining can be distinctly identified without masking each other. The results showed that 37 (93%) of 40 cases displayed positive nuclear staining for ER, cytoplasmic staining for mammaglobin, or a combination of both. Only 3 cases were double negative for both mammaglobin and ER.

Conclusions: This study establishes the practical utility of a mammaglobin and ER cocktail. The high sensitivity (93%) highlights the cocktail as a novel diagnostic tool for identifying a metastasis of unknown primary as breast origin in a biopsy setting with limited tissue. This is important given the therapeutic options this information provides.

CD10 Immunoreactivity in Atypical Fibrous Xanthoma and Malignant Fibrous Histiocytoma

(Poster No. 33)

Jacqueline J. Russo, MD (russjj@pathology.ufl.edu); Keira L. Barr, MD; Vladimir Vincek, MD. Department of Pathology, University of Florida, Gainesville.

Context: Atypical fibrous xanthomas (AFXs) and malignant fibrous histiocytomas (MFHs) have characteristically been regarded as diagnoses of exclusion. To some, AFXs and MFHs are 2 ends of the same spectrum. AFXs are considered superficial MFHs to some, whereas they remain distinct entities to others. In the past, AFXs have been shown to be strongly immunoreactive for CD10; however, to the best of our knowledge, MFHs have not been formally explored for CD10 immunoreactivity. Therefore, this study is designed to investigate and compare CD10 immunoreactivity in AFXs and MFHs.

Design: Seven cases of AFX and 15 cases of MFH were obtained from the University of Florida/Shands Hospital archival files. Each was stained with prediluted monoclonal antibody CD10 (Ventana, Tucson, Ariz), and their reactivity was quantified.

Results: Our study showed that 7 (100%) of 7 AFXs and 15 (100%) of 15 MFHs stained strongly positive for CD10.

Conclusions: To the best of our knowledge, this is the first study to compare CD10 immunoreactivity in MFHs to that in AFXs. Both AFXs and MFHs are strongly and diffusely immunopositive for CD10. These results further support the notion that AFXs and MFHs are likely one in the same and that AFXs are perhaps better designated as superficial MFHs.

Mammary Paget Disease and Extramammary Paget Disease: Two Morphologically Similar but Biologically Different Diseases

(Poster No. 34)

Weiguo Liu, MD, PhD1 (wliu2@buffalo.edu); Jabad Iqbal,MD2;Madhat Arnouk, MD2; Thaer Khoury, MD.2 1Department of Pathology, State University of New York at Buffalo; 2Department of Pathology, Roswell Park Cancer Institute, Buffalo, NY.

Context: Mammary Paget disease (MPD) and extramammary Paget disease (EMPD) are uncommon intraepidermal epithelial neoplasms. The cells of origin in MPD and EMPD have been the subject of controversy. The purpose of this study is to examine tumor expression of the members of HER-2 pathway.

Design: HER-2, AKT, pAKT, pTEN, epidermal growth factor receptor (EGFR), and pEGFR were examined in 16 MPD cases and 14 EMPD cases. HER-2 was graded on a scale from 0 to 3. Scores ≥2 were considered positive. For AKT, pAKT, pTEN, EGFR, and pEGFR, a semiquentitative scoring system was used. Scores 100 were considered positive. Fisher exact test was used to analyze the data.

Results: HER-2 was positive in 14 (87.5%) of 16 MPD and 5 (35.7%) of 14 EMPD cases. While AKT was expressed in all cases, pAKT was expressed in 14 (87.5%) of 16 MPD and in 13 (92.9%) of 14 EMPD cases. Both EGFR and pEGFR were negative in all cases. pETN was positive in 10 (62.5%) of 16 MPD and 10 (71.4%) of 14 EMPD cases. For the pAKTpositive group, see the Table for expressions of HER-2 and pTEN. HER-2-negative/pTEN-positive were recorded in 0 (0%) of 14 MPD and 5 (38.5%) of 13 EMPD (P = .04) cases.

Conclusions: In a subset of EMPD, Akt is not activated by HER-2 overexpression or by loss of pTEN, which is not the case in MPD. Although the sample tested is small, these preliminary data support the notion that these tumors are biologically different. A larger cohort is needed to validate these findings.

Does a Decrease in Cutaneous Melanin Increase the Risk of Developing Melanoma With Exposure to UV Light?

(Poster No. 35)

Tim J. Gallagher, MD, MHSA (tim.gallagher@bhsala.com). Department of Pathology, Baptist Health System, Birmingham, Ala.

Context: According to the data published, exposure to UV radiation is the major risk factor for development of melanoma. The risk of melanoma and the amount of melanin in skin are reported to be inversely proportional. That being the case, it compels one to the conclusion that albinos, devoid as they are of melanin in general, should develop melanomas at a higher frequency than their pigmented counterparts. This should be especially evident among black African oculocutaneous albinos who cannot escape the deleterious daily effects of the sun's rays. Is that the actuality?

Design: Between 1975 and 1993, 5 major epidemiologic studies regarding skin cancers in albinos were undertaken in persons living on the African continent. In these studies were enrolled both normally pigmented black Africans and albino black Africans. A total of 1482 albino black Africans participated in the studies (Table).

Results: One melanoma within the albino population (0.067%) was identified. It was situated on the perineum, a site covered consistently by clothing. The percentage of melanomas diagnosed in their black African counterparts was 0.9%. The incidence of melanoma in normally pigmented versus nonpigmented populations of the same race living in identical environments is significantly greater in the pigmented individuals.

Conclusions: Melanomas are uncommon in albinos, despite their extensive exposure to sunlight. It is inferred from the data that melanomain albinos is extremely rare and is not caused by sunlight. From that conclusion, we can further infer that melanoma in humans, irrespective of their color, is not brought into being by ultraviolet radiation alone.

A Case of Adult Solitary Cutaneous Myofibroma

(Poster No. 36)

C. A. Arnold, MD1 (carnold77@gmail.com); J. S. Susa, DO2; C. J. Cockerell, MD.2 Departments of 1Pathology and 2Dermatology, University of Texas Southwestern, Dallas.

Adult solitary cutaneous myofibroma has been described relatively recently as a lesion with a propensity for the extremities of middle-aged men that is most often associated with a benign clinical course. TheWorld Health Organization's most recent histologic description of myofibroma includes the following: an overall nodular or multinodular architecture that is composed of a proliferation of 2 types of cells. Generally, the periphery of the lesion is characterized by nodular growth of plump, spindle-shaped myofibroblasts that are arranged in fascicles or whorls. The center of the lesion generally comprises more immature-appearing cells, with larger, hyperchromatic nuclei and scant cytoplasm. These less mature-appearing cells surround thin-walled, irregularly branching, or staghorn-type, vasculature channels. We report a case of adult solitary cutaneous myofibroma from a lesion on the lower extremity of a middleaged man. The lesion had a multinodular configuration with prominent hyalinization of the stroma of the spindled cells, a focus of calcification, and immature-appearing cells surrounding staghorn vessels percolating throughout the lesion and around the perimeter. Of importance, in addition to the immature cellular elements, adult solitary cutaneous myofi-bromas can be associated with necrosis and intravascular growth and, uncommonly, with increased mitotic activity, features which can lead to the misdiagnosis of a malignant process. In order to avoid the pitfall of misdiagnosing adult solitary cutaneous myofibroma as a malignant lesion, the characteristic features are reviewed. The demographics, the differential diagnosis, and useful immunohistochemical stains will be discussed.

Detection of ABCB5 in Primary Melanoma Using Real-Time Reverse Transcription-Polymerase Chain Reaction on Routine Specimens

(Poster No. 37)

Emily A. Bantle, MD1 (ebantle@path.wustl.edu); Eric Duncavage, MD, PhD1; Robert Jarrett, MD1; Jochen Lennerz, MD, PhD1; M. L. Council,MD2; Anne Lind, MD1; John Pfeifer, MD, PhD.1 Departments of 1Pathology and Immunology and 2Dermatology, Washington University, St Louis, Mo.

Context: The crucial role of adenosine triphosphate-binding cassette transporter family (ABCB5) has recently been solidified via xenotransplantation experiments, showing the enhanced tumorigenicity of ABCB5-expressing melanoma cells. Given that ABCB5 also confers chemoresistance to doxorubicin in human melanoma, the practicality of ABCB5 analysis in the routine pathology setting via immunohistochemistry is of interest.

Design: RNA was extracted from 14 patients with primary melanoma using routine formalin-fixed, paraffin-embedded tissue from our files. Subsequent SYBR green-based one-step reverse transcription-polymerase chain reaction and melting curve analysis were performed in 3 independent experiments. Population characteristics were as follows: 8 men and 6 women, ranging in age from 35 to 75 years, with average follow-up of 35.5 months (8 alive), and T stages T1 (n = 3), T2 (n = 2), T3 (n = 3), and T4 (n = 6).

Results: ABCB5 expression was detected in 8 of 14 patients, whereas all cases showed actin amplification. Of the 8 patients with detectable ABCB5, 3 were deceased, 4 had lymph node metastases, and 4 had tissue metastases. Multivariate regression analysis showed ABCB5 to be positively correlated with advanced T stage (coefficient, 0.465; P = .004, R2 = 0.649). However, population size was too small to detect a significant difference with respect to lymph node metastasis, tissue metastasis, or survival status.

Conclusions: Expression analysis from routine formalin-fixed, paraffinembedded tissue using reverse transcription-polymerase chain reaction is feasible, reliable, and offers a sensitive way to detect ABCB5 in human melanoma. Delineation of the relationship of ABCB5 expression with stage, survival, or drug sensitivity will continue, necessitating the development of straightforward assays for measuring ABCB5 expression.

Left Groin Mass in a 37-Year-Old Man: A Case Study With Possible Role of Sentinel Lymph Node Biopsy in Hidradenocarcinoma

(Poster No. 38)

John H. Irlam, DO1 (john.irlam@utoledo.edu); Summer L. Bohman, MD1; Jean E. Thomas, MD1,2; Robert L. Booth, MD1; Hollis Merrick, MD.3 Departments of 1Pathology and 3Surgery, University of Toledo Medical Center, Toledo, Ohio; 2Pinkus Dermatopathology Laboratory, Toledo, Ohio.

Hidradenocarcinoma (malignant hidradenoma) is a rare, malignant adnexal tumor of sweat gland origin that most commonly occurs on the face and extremities. This tumor tends to be locally aggressive and has frequent metastases to regional lymph nodes as well as extensive local recurrence. While the utility of sentinel lymph node biopsy is widely accepted in the staging of metastatic melanoma, its usefulness in determining the prognosis in high-risk nonmelanoma skin tumors, such as hidradenocarcinoma, has yet to be adequately defined. Because of the rarity of this tumor, few studies have been performed to evaluate the effectiveness of sentinel lymph node biopsy in early detection of metastatic disease. To date, metastatic disease is usually treated by regional lymph node dissection and localized wide excision of the primary lesion. In this case study, we present a 37-year-old man with a 16-year history of left groin mass. Initial excisional biopsy revealed a sweat gland carcinoma with lobules of polygonal cells with nuclear atypia separated by dense fibrosis with both squamous and ductal differentiation. These features were consistent with hidradenocarcinoma. Subsequent sentinel lymph node biopsy, regional lymph node dissection, and wide local reexcision did not demonstrate any residual tumor, and the patient remained disease free during 30 months of postsurgical surveillance. It is our hope that this presentation may help to further define the role of sentinel lymph node biopsy in highrisk nonmelanoma skin tumors, especially those of sweat gland origin.

Quantifying the Degree of Dysplasia in Dysplastic Nevi

(Poster No. 39)

Amy Paul, MD (hsasken@gmail.com); Ronaldo Zamuco, MD; Harvey Sasken, MD. Department of Pathology, Lincoln Medical Center, Bronx, NY.

Context: Cytologic atypia was not a feature of dysplastic nevi as first described. Clinicians now request the degree of cellular atypicality be assessed.

Design: Fifteen consecutively accessioned lesions were evaluated by computerized image analysis. We examined 100 representative cells from each biopsy. Parameters measured included the following: (1) Nuclear size-nuclear membranes were isolated from the surrounding cytoplasm and the enclosed areas generated. (2) Nuclear shape factor or the ratio of area to perimeter is expressed as a number from 0 to 1-1 represents the highest ratio possible, or a perfect circle; 0 represents a perimeter with no area, such as an irregular line. The more irregular the shape, the lower the number. (3) Percentage of cells with a demonstrable nucleolus. (4) Nucleolus size. (5) Distribution of nuclear chromatin, a densitometricmeasurement by grayscale analysis of the degree of clumping of the chromatin. Homogeneous nuclei have a bell-shaped distribution; irregular nuclei have a disparate distribution. The continuous range is then divided into dark, medium, and light areas, each of which is expressed as a percentage.

Results: Nuclear size ranged from 48.2 to 106.3 µm2. Nuclear shape factor was 0.812 to 0.216. Percentage of cells with nucleolus was 9% to 38%. Nucleolus size was 13.1 to 24.7 µm2. Chromatin density distribution was 81%, 16%, 3% to 36%, 43%, and 21%.

Conclusions: Dysplasia in dysplastic nevi can be quantified and assigned to mild, moderate, and severe categories. Further work should produce nuclei typical of each category. Published photomicrographs will aid in assigning clinical cases.

Anaplastic Large Cell Lymphoma Masquerading as Amelanotic Nodular Melanoma, or How Immunohistochemistry Saved the Day

(Poster No. 40)

Amanda C. Mullins, MD1 (amullin3@utmem.edu); Diane L. Mullins, MD.2 1Department of Pathology and Laboratory Medicine, University of Tennessee, Memphis; 2Department of Pathology, PML Pathology, Asheville, NC.

Melanoma can mimic virtually any neoplasm, and thus is in the differential diagnosis of most tumors, although it usually can be excluded by clinical presentation, histologic appearance or, if necessary, immunohistochemical stains. Rarely, analysis of a tumor which by clinical presentation and histology appears to be melanoma leads to an unexpected diagnosis. We present a case of an indurated nodule on the left arm of a 78-year-old white man. Histologic examination revealed a dome-shaped nodule composed of cohesive, biphasic (epithelioid and spindled) malignant cells arising in sun-damaged skin. The individual tumor cells were large with pleomorphic nuclei with nucleoli and were arranged in sheets and short fascicles. Nodular aggregates of lymphocytes were present within and adjacent to the tumor. Reparative epidermal changes were present. Intraepidermal melanocytes were not easily identified. With a working diagnosis of amelanotic nodular melanoma, immunohistochemical stains for S100, Melan-A, and pancytokeratin were performed. Perplexingly, all were negative. Therefore, additional stains for myeloid and lymphoid cells were applied including B-lymphocyte and T-lymphocyte markers. The only positive marker in the malignant cells was LCA (CD45). Subsquent stains, including CD30, were then performed, establishing the tumor as a CD30-positive anaplastic lymphoma. Prudent investigation of a malignancy posing as melanoma with some atypical histologic features and directed application of immunohistochemical stains unmasked this melanoma mimic.

Basal Cell Carcinosarcoma

(Poster No. 41)

Roy Nambudripad, MD (rnambudr@uci.edu); Tomomi L. Billings, MD; Yevgeniy Karamurzin, MD; Mark L. Wu, MD. Department of Pathology, University of California, Irvine, Orange.

We present the first case of Bcl-2 positivity in both components of a carcinosarcoma arising from a basal cell carcinoma. An 81-year-old man with chronic obstructive pulmonary disorder, atrial fibrillation, peripheral vascular disease, and no known history of prior malignancy presented with an ulcerated, exophytic, and dome-shaped lesion on the left side of his face that measured 1.7 1.1 cm. Excision revealed a biphasic tumor that consisted of nodular type of basal cell carcinoma intermixed with atypical mesenchymal cells and numerous atypical mitoses (Figure 40). Half of the tumor was basal cell carcinoma, nodular type, and the other half consisted of a spindle cell sarcoma. These findings were consistent with a diagnosis of carcinosarcoma originating from a basal cell carcinoma. An adjacent, intradermal melanocytic nevus was found. Lymphovascular/perineural invasion was absent. The malignant epithelial component was positive for low-molecular-weight keratin (AE1/AE3), Bcl-2, Ber EP4, p53, and CK5/6. The malignant stromal component was positive for Bcl-2, p53, and vimentin. The low-molecular-weight keratin was negative in the mesenchymal component, and S100, Melan-A, HMB-45, CD117, epithelial membrane antigen, smooth muscle actin, H-caldesmon, and CD34 were all negative in both components (all immunoreagents from Dako, Carpinteria, Calif). This evidence supported our diagnosis over malignant melanoma, peripheral nerve sheath tumor, gastrointestinal stromal tumor, and solitary fibrous tumor, as well as dermatofibrosarcoma protuberans, leiomyosarcoma, synovial sarcoma, angiosarcoma, and myofibroblastic or epithelioid sarcoma. In addition, Bcl-2 positivity in both components strongly suggested that the sarcoma arose from the basal cell carcinoma.

Linear Epidermal Nevus Presenting at Unusual Site

(Poster No. 42)

Kanu Goel, MBBS, MD1 (kanugoyal@yahoo.com); Sanjeev Gupta, MBBS, MD2; Aneet Mahendra, MBBS, MD.2 Departments of 1Pathology and 2Dermatology, Maharishi Markandeshwar Institute of Medical Sciences and Research, Mullana (Ambala), Ambala, India.

A 21-year-old man presented with wartlike lesions in the genital region. Genital examination revealed linear rows of papillomatous, wartlike lesions on the right side of the scrotum. A skin biopsy measuring 0.7 0.5 cm resembled benign fibroepithelial polyps histologically, with considerable hyperkeratosis, papillomatosis, and acanthosis with elongation of rete ridges. (Figure 41, hematoxylin-eosin, 200). In linear epidermal nevus, the changes may be histologically nonspecific, and viral warts and acanthosis nigricans are important in the differential diagnosis. Lesions in linear epidermal nevus may be small and solitary or multiple and frequently have a linear morphology following Blaschko lines. The linear arrangement of lesions in this case and the nonexistence of typically brown to black hyperpigmented skin patches favored the diagnosis of linear epidermal nevus. Anogenital warts show papillomatosis, hyperkeratosis, parakeratosis, considerable acanthosis, and elongation of rete ridges along with the presence of kiolocytotic cells (cells with distinct perinuclear vacuolization) in the deeper portions of stratum Malpighi, which were typically absent in this case. As there are reports of malignancy and syndromic association in linear epidermal nevus, it is important to differentiate linear epidermal nevus from acanthosis nigricans warts; also, the treatment modalities are different. To conclude, linear epidermal nevus in the genital area is rare and should not be mistaken for warts.

Bandlike Amyloid Deposition in Bowenoid Papulosis

(Poster No. 43)

Rashmi K. Shamanna, MD (rshaman1@hfhs.org); Ziying Zhang, MD; Frank Torres, MD; Min W. Lee, MD. Department of Pathology and Laboratory Medicine, Henry Ford Hospital, Detroit, Mich.

Localized primary cutaneous amyloid is characterized by deposit of keratin-derived amyloid fibrils in papillary dermis. It occurs as a result of apoptosis of normal or neoplastic keratinocytes. Deposit in macularamyloid is in small groups of dull pink globules that become confluent to form papule or plaque. Amyloid deposit in basal and squamous cell carcinomas and seborrheic keratosis is in the intervening stroma between nests of neoplastic cells. Linear bandlike deposition of amyloid is a rare occurrence that is mainly in association with in situ squamous cell carcinomas. A 58-year-old woman presented with a 5-year history of a papule on the right labia majora. The biopsy revealed full-thickness involvement of atypical squamous epithelium that was recognized as Bowenoid papulosis. Also, there was abundant subepidermal bandlike pale eosinophilic deposit that was positive for Congo red with apple green birefringence. Thioflavin T and ultrastructural studies confirmed the deposit as amyloid. Cytokeratin was weakly positive in the amyloid. Diagnosis was made as Bowenoid papulosis with bandlike amyloid deposition at the epidermal-dermal junction (Figure 42). The rare bandlike deposition of amyloid has been described in macular amyloidosis and solar keratosis. In our case, the amyloid deposit is sharply restricted to subepidermal area affected by dysplasia. Positive cytokeratin supports the currently accepted mechanism of amyloid deposition due to abnormal apoptosis of neoplastic keratinocytes. This bandlike amyloid deposit in Bowenoid papulosis may be related to accelerated apoptosis, which may explain the spontaneous resolution in many cases. The exact mechanism remains to be elucidated.

Occult Hürthle Cell Carcinoma of the Thyroid Presenting as a Metastatic Orbital Mass

(Poster No. 44)

Loren P. Herrera, MD1 (lherrera@med.miami.edu); David Tse, MD2; Jocelyn Bruce, MD.1 1Department of Pathology, University of Miami/Jackson Memorial Hospital, Miami, Fla; 2Department of Ophtalmology, University of Miami/Bascom Palmer Eye Institute, Miami, Fla.

Hürthle cell carcinoma (HCC) accounts for 3% to 4% of thyroid malignancies. HCC has a higher incidence of metastasis at the time of diagnosis compared with other variants of follicular and papillary carcinoma. The most common sites of metastasis are ipsilateral cervical lymph nodes, lung, and bone. We report a case of HCC presenting as a destructive lesion of the orbital roof and extraocular muscles. A 65-year-old woman with a history of lumpectomy for breast cancer and hemithyroidectomy for Graves disease presented with increasing proptosis. Imaging studies revealed an erosive bony lesion involving the left orbital roof and lateral orbital wall. She underwent surgical resection with a presumptive diagnosis of metastatic breast cancer versus meningioma. Histologically, multiple colloid-filled follicles lined by cuboidal oncocytic cells with pleomorphic nucleus, conspicuous nucleoli, and high nuclear to cytoplasmic ratio were found infiltrating bone and skeletal muscle. Perineurial, lymphovascular invasion, and mitosis were not identified. Immunostains for TTF-1 and thyroglobulin were positive, whereas estrogen and androgen receptors were negative. Subsequent resection and pathologic examination of the remaining thyroid confirmed the diagnosis of HCC. No cervical lymph node involvement was identified. Orbital metastasis is a rare event in thyroid malignancies. We are unaware of previous reports of HCC of the thyroid presenting as metastatic disease to the orbit, and we could find no reference to such a case in a computerized search using MEDLINE.

A Comparison of Endocrine Cells Before and After Surgery in Patients Having Gastric Outlet Procedure

(Poster No. 45)

Christopher P. Kragel, MD (kragelc@ecu.edu); Terri S. Giles, MD; Peter Kragel, MD. Department of Pathology and Laboratory Medicine, Brody School of Medicine, Greenville, NC.

Context: Some diabetic patients who are morbidly obese experience correction of their hyperglycemia following gastric outlet surgery. The rapidity of this correction suggests that more than just weight loss is involved.

Design: Thirty gastric biopsies from patients before the gastric outlet procedure (GOP), 18 gastric biopsies from patients after the GOP, and 10 control gastric biopsies were identified. Hematoxylin-eosin-stained sections were reviewed. Immunoperoxidase stains were performed using primary antibodies to chromogranin A (mouse monoclonal LK2H10, Bio-Genex Laboratories Inc, San Ramon, Calif), somatostatin (polyclonal rabbit, DAKO, Carpinteria, Calif), and glucagon (polyclonal rabbit, DAKO), and standard staining methodology. The histopathologic diagnosis and number of positively staining cells per high-power field for each antibody were determined. Statistical analysis was performed using the 2-tailed t test.

Results: There was no statistically significant difference in numbers of positively staining cells when all pre-GOP biopsies and all post-GOP biopsies were compared and when only cases that included gastric body mucosa were compared. Cases that showed changes of reactive/chemical gastropathy showed a pre-GOP somatostatin mean count of 24.1 positive cells versus a post-GOP count of 10.2 (P = .02). Comparison of positive staining in pre-GOP and post-GOP cases showing chronic inactive gastritis and chronic active gastritis was not significant.

Conclusions: Changes in endocrine cell composition of the gastric body mucosa occur following gastric outlet surgery for morbid obesity. Further studies are recommended to determine if such changes contribute to correction of hyperglycemia in these patients.

Postverification Errors in a Community Hospital

(Poster No. 46)

Eugene S. Pearlman, MD (czaroflabs@aol.com); Melissa Haygood, MT(ASCP); Stanley Sprei, MD. Department of Pathology, Lourdes Hospital, Paducah, Ky.

Context: The problem of postverification errors with wrongly reported results is a vexing one for the clinical laboratory. Efforts to quantify the problem depend on notification of the clinical laboratory by nonlaboratory personnel. We attempted an independent assessment by detecting discrepant results within serial troponin assays from inpatients undergoing cardiac catheterization.

Design: We evaluated data from the electronic medical records of 385 consecutive inpatients from the first quarter of 2007 who underwent caridac catheterization. Of these, 343 (89%) representing 1352 inpatient days had 2 or more troponin concentrations. Sampling was done from primary bar-coded tubes using an ultrasensitive troponin assay according to manufacturer's directions (Siemens, Tarrytown, NY). The laboratory had a delta check protocol in place. Expected variation was estimated from quality control data.

Results: Five patients had discrepant results in their precatheterization troponin results with an outcome that differed from a previous result by more than 5.5 SDs for a rate of 3.7 postverification error events per 1000 inpatient days. Regarding the patient days represented by this population as a sample of total patient days during the first quarter of 2007 and using a ratio estimation technique, the expected number of such events for this 3 month period (44±7) greatly exceeded the actual number (8) coming to the attention of the laboratory during this time period.

Conclusions: The actual number of postverification errors may be significantly greater than the number communicated to the laboratory.

Endoscopic Ultrasound-Guided Fine-Needle Aspiration Is Useful in the Diagnosis of Sarcomas

(Poster No. 47)

Min Yi Ngae, MD1 (myngae@gmail.com); Clinton D. Crowder, MD1; Edward B. Stelow, MD2; H. Evin Gulbahce, MD1; Stefan E. Pambuccian, MD.1 1Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis; 2Department of Pathology, University of Virginia, Charlottesville.

Context: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) has become an established method in diagnosing primary and metastatic epithelial malignancies of the pancreas, liver, mediastinum, and other EUS-accessible organs. Recent evidence suggests EUS-FNA is useful in the diagnosis of lymphoproliferative disorders, but its utility in sarcoma diagnosis has not been addressed. We review our experience with EUS-FNA in the diagnosis of sarcomas.

Design: We searched the cytopathology databases of 2 institutions from January 1, 2004, to August 30, 2007, for EUS-FNA with unequivocal diagnosis of sarcoma. The slides were retrieved and reviewed. Patient age, sex, previous malignancy, location of primary tumor, and EUS-FNA site were recorded. In all cases, EUS-FNA was performed with a cytopathologist on site, and cell blocks were made. Immunoperoxidase stains were performed on 5 of the cases.

Results: During this interval, we identified 8 cases with an unequivocal diagnosis of sarcoma. The EUS-FNA sites were as follows: 4 pancreatic, 1 mediastinal, 1 esophageal, 1 retroperitoneal, and 1 gastric. Four patients had a history of sarcoma. In one of the remaining patients, a renal transplant recipient, EUS-FNA established the diagnosis of Kaposi sarcoma, which subsequently was found to involve renal allograft. See the Table.

Conclusions: A cytopathologic diagnosis of sarcoma is possible on EUS-FNA, even in patients without a known primary sarcoma. Accurate diagnosis of sarcoma can be made by EUS-FNA and allows institution of therapy without additional biopsies.

Molecular Chaperone Expression During Breast Cancer Progression

(Poster No. 48)

Katherine N. Kimmelshue, MD1 (kkimmelshue@mcvh-vcu.edu); Malissa Diehl, BS2; Michael O. Idowu, MD, MPH1; Shawn E. Holt, PhD1; Lynne W. Elmore, PhD.1 Departments of 1Pathology and 2Human Genetics, Virginia Commonwealth University, Richmond.

Context: Molecular chaperones are proteins that bind to and stabilize client proteins by controlling folding, assembly, and transport. Our laboratory has previously shown that the molecular chaperone protein hsp90 and its co-chaperone p23 are overexpressed in prostate carcinoma and prostatic intraepithelial neoplasia but not in benign prostatic hypertrophy. The aim of this study was to characterize hsp90 and p23 expression in breast cancer progression.

Design: Six pairs of unstained tissue microarray slides were obtained from the National Cancer Institute Cooperative Breast Cancer Tissue Resource. The slides were stained with anti-hsp90 and anti-p23 antibodies (provided by Dr David Toft, Mayo Clinic, Rochester, Minn) and scored by 2 pathologists for intensity and localization. Each slide contained 130 to 137 cores, consisting of variable numbers of cores containing normal breast tissue (including fibrocystic changes), ductal carcinoma in situ, node-positive invasive breast cancer, node-negative invasive breast cancer, and metastatic breast cancer. Statistical analysis was done using SAS PROC GENMOD software (SAS, Cary, NC).

Results: See the Table for staining patterns. Significant differences in p23 nuclear expression between normal tissue, ductal carcinoma in situ, and invasive cancer were observed (P = .008). Nuclear p23 expression weakened with progression to invasive cancer. P values for hsp90 nuclear staining, hsp90 cytoplasmic staining, and p23 cytoplasmic staining between normal tissue, ductal carcinoma in situ, and invasive cancer were insignificant at .954, .151, and .374, respectively.

Conclusions: hsp90 and p23 do not seem to be involved in breast cancer progression. It appears that p23 expression actually decreases with breast cancer progression.

POSTER SESSION 500: SATURDAY, SEPTEMBER 27, 2008, 10:00 AM-12:30 PM

Clinical Chemistry; Clinical Immunology; Gynecologic and Placental Pathology; Microbiology; Pulmonary and Mediastinal Pathology

Making Creatinine Standardization a Reality: One Laboratory's Experience

(Poster No. 1)

Paul J. McGowan, MD (mcgowanpj@health.missouri.edu); Alan Luger, MD. Department of Pathology and Anatomical Sciences, University of Missouri-Columbia.

Context: The importance of creatinine standardization has been addressed in recent literature.

Design: Our laboratory measured serum creatinine using a kinetic alkaline picrate technique. A nonstandardized method (MC) and a standardized method (sAC) were compared using the National Institute of Standards and Technology's standard reference material (SRM) 967 (level 1 = 0.753 mg/dL; level 2 = 3.916 mg/dL). Both methods were used to test 47 patient samples. A novel calibration method (SRM 967 Cal), which used the 2 SRM 967 standard levels as calibrator points, was created and tested. Estimated glomerular filtration rates (eGFRs) were calculated from each method and compared.

Results: The mean of sAC level 1 (0.73 mg/dL, SD = 0.031) was lower than the SRM 967 (P = .01), and the mean of sAC level 2 (3.85 mg/dL, SD = 0.063) was higher than the SRM 967 (P < .001). The means of the MC results (0.90 mg/dL, SD = 0.0; 3.85 mg/dL, SD = 0.065) were both higher than SRM 967 levels (level 2; P < .001). The sAC method was negatively biased compared with the MC (-0.226 mg/dL, p for y intercept < 0.0001) and the experimental SRM 967 Cal (-0.306 mg/dL, p for y intercept < 0.0001) methods. Finally, the eGFRs calculated from creatinine values derived from MC and sAC were not statistically or clinically different from one another (P < .001; Table).

Conclusions: The standardized sAC method yields lower creatinine values than the nonstandardized MC method. Standardization did not have a significant effect on eGFRs calculated using the appropriate formulae.

Urinalysis in Geriatric Patients With Urinary Tract Infection

(Poster No. 2)

Rita H. Khoury, MD1 (rkhoury@aculabs.com); B. P. Salmon, MS1; Asha Gandhi, BS1; Irina Y. Ryzhkova, BS1; Peter Gudaitis, BS1; Dauna Gudaitis, BS1; Patrick Sluss, PhD.2 1Aculabs Inc, East Brunswick, NJ; 2Department of Chemistry, Massachusetts General Hospital, Boston.

Context: Urinary tract infection (UTI) is very common among the geriatric population and can cause serious complications. Urinalysis is an invaluable tool in the diagnosis of UTI; this study examined the results of automated urinalysis compared with a reference culture procedure to identify UTI in a geriatric population.

Design: One thousand thirty-five specimens were collected for urine cultures and urinalysis from residents in long-term care facilities. Urinalysis was done using Urisys 2400 (Roche Diagnostics, Indianapolis, Ind); the tests used were nitrate, leukocyte estrase alone or in combination with nitrate, and erythrocyte. A test was considered positive if the results indicated a trace or greater. We calculated the sensitivity, specificity, and likelihood ratio (positive and negative). The culture was done using MicroScan (Siemens, Tarrytown, NY). We used urine culture as the reference standard. No growth or <10 000 colony-forming units/mL were considered negative; cultures with 50 000 colony-forming units/mL were considered positive.

Results: Five hundred twenty-seven (50.9%) of the cultures were negative, 470 (45.4%) were positive, and 38 (3.7%) were contaminated (Table).

Conclusions: More than 45% of the urine specimens collected tested positive for UTI by culture. Automated nitrate and "either nitrate or leukocyte" were helpful to rule in UTI, but none of the automated tests examined could rule out UTI. The "either leukocyte or nitrate" combination was useful but did not provide convincing diagnostic evidence that a negative test result indicates the absence of UTI (rule-out). Physicians should be aware of the limitations of urinalysis, and it should not be used alone to screen for UTI.

Methylmalonic Acid as a Marker of Vitamin B12 Deficiency in End-Stage Renal Disease

(Poster No. 3)

David Azar, MD1 (dazar@ucsd.edu); David Herold, MD, PhD1; Scott Mullaney, MD2; Robert Fitzgerald, PhD.1 Departments of 1Pathology and 2Medicine, Veterans Affairs San Diego Healthcare System/University of California, San Diego.

Context: Serum cobalamin (B12) concentrations frequently do not accurately reflect functional tissue vitamin B12 stores, leading to underdiagnosis of B12 deficiency. Serum methylmalonic acid (MMA) is a sensitive and specific surrogate for tissue B12 status. Despite supplementation, B12 deficiency remains a problem in end-stage renal disease (ESRD) patients. This study aims to establish the MMA dialysis clearance rate and to develop a model to correct for renal function when using MMA as a B12 surrogate in ESRD patients.

Design: Prehemodialysis and posthemodialysis serum specimens were obtained from 50 ESRD patients. MMA concentrations were determined by isotope dilution liquid chromatography-tandem mass spectrometry. MMA values were correlated to serum B12 concentrations. Dialysis clearance was evaluated in comparison to blood urea nitrogen using the urea reduction ratio, a standard measure of dialysis efficiency.

Results: Methylmalonic reduction ratios (0.75 ± 0.07) were not significantly different from urea reduction ratios (0.7 ± 0.06) (P = .40). Predialysis MMA values were elevated above the upper normal limit (0.4 µmol/L) for all but one test subject (average, 0.95; range, 0.27-2.21 µmol/L), whereas all postdialysis values were <0.4 µmol/L. All serum B^sub 12^ concentrations were above the normal reference value (209 pmol/L). Elevated MMA was correlated to B^sub 12^ concentration, especially B^sub 12^ < 500 pmol/L (R^sup 2^ = 0.66).

Conclusions: Dialysis clearance of MMA was similar to blood urea nitrogen. MMA was correlated to B12, particularly for B12 < 500 pmol/L, suggesting B12 tissue deficiency in a portion of these patients. Further work monitoring MMA concentrations following B12 supplementation in patients with lower B12 values will elucidate the true number of tissuedeficient patients.

Vitamin D Deficiency Among Middle Eastern Females Wearing Hijab and Not Regularly Exposed to Direct Sunlight

(Poster No. 4)

Syed S. Ahmed, MD1 (taahas@yahoo.com); Dick J. Burger, MSc1; Mohammad Al Maki, MSLO1; Fayssal Farahat, MD.2 Departments of 1Pathology and 2Preventive Medicine, Al-Hada and Taif Military Hospital, Taif, Saudi Arabia.

Context: This study aims to assess the prevalence of vitamin D deficiency and to investigate the possible correlation between 1,25-dihydroxycalciferol and serum calcium levels in a female population wearing hijab covering face and hands and not regularly exposed to direct sunlight.

Design: Serum 1,25-dihydroxycalciferol and total calcium levels of 56 female patients wearing complete hijab were retrospectly analyzed. Ages ranged from 8 to 79 years. The mean (standard deviation) was 40.4 (21.7) years. The study group was randomly assigned to age groups younger and older than 40 years. Serum 1,25-dihydroxycalciferons were determined by a standard radioimmunoassay. The total calcium analysis was performed on the Abbott Architect Tracking System (Abbott Laboratories, Abbott Park, Ill), using the Arsenazo 3 photometric principle.

Results: Sixty-two percent of the patients had vitamin D deficiency (<20 nmol/L), and 36.4% had vitamin D insufficiency (20-63 nmol/L). The mean serum calcium level was 2.67 nmol/L. Vitamin D levels positively correlated with serum calcium levels; however, the correlation was not significant (r = 0.1). In this preliminary study, with limited data, there was a significant, positive relation (P κ .05) between increasing age of the study subjects and calcium levels that are in accordance with basic physiology.

Conclusions: Despite the small sample size, this study reveals a higher prevalence of vitamin D deficiency among young females wearing complete hijab. Insufficient sunlight exposure may be the main contributing factor; however, further study is required among a healthy population to assess risk factors of vitamin D deficiency among young females wearing complete hijab.

Use of Multiple Patient Analyte Samples to Enhance Detection of Changing Clinical Status

(Poster No. 5)

Sara C. Koenig, MD (sara.koenig@bmc.org); Martin H. Kroll, MD. Department of Laboratory Medicine, Boston Medical Center, Boston, Mass.

Context: When comparing results over time, biologic variation must be statistically incorporated into the evaluation of values to identify a physiologic change. Traditional methods compare the difference in 2 values with the standard deviation (SD) to indicate whether a "true" physiologic change has occurred.

Design: The standard test for change compares the difference between 2 points with the 95% confidence limit, given as ±1.96SD[the square root of]2. In reality, this represents the calculation of the standard error of the difference for 2 points separated in time. We examined the effect of multiple data pairs on the confidence limit.

Results: If one initially has 1 data point and later obtains 2 additional data points, two difference pairs are present, for which the confidence limit is 1.96 SD, which is 40% less than that calculated from2 individual data points. Increasing the number of data pairs further reduces the size of this confidence limit (Figure 43). The formula to incorporate n data pairs is 1.96SD[the square root of]2/n.

Conclusions: Evaluating the clinical significance of multiple paired sets of patient data, rather than a single pair, results in a substantial decrease in the confidence interval, thereby improving the sensitivity of the evaluation. A practice of using multiple patient samples results in enhanced power to detect true changes in patient physiology. Such a testing protocol is warranted when small changes in the analyte precede serious clinical events or the SD of the biologic variation is large.

Incorporation of a Periodic Function: An Alternate Approach to Insulin Monitoring

(Poster No. 6)

Sara C. Koenig, MD (sara.koenig@bmc.org); Martin H. Kroll, MD. Department of Laboratory Medicine, Boston Medical Center, Boston, Mass.

Context: The predominant model of biologic homeostasis assumes that deviations from an individual's physiologic set point result from random fluctuation. Accordingly, the standard deviation (SD) is used to quantify biologic variation and to evaluate for the presence of physiologic change. Insulin demonstrates nonrandom periodic behavior; therefore, use of the SD is not applicable. As an alternate approach, we use a sine function to characterize insulin values.

Design: We examined a previously published set of serial data for insulin values. We plotted the values sequentially and calculated the SD of the data and of the residuals after subtracting a fitted sine function.

Results: The 119 insulin values were oscillatory, nonrandom and deterministic, and corresponded well to a fitted sine function (Figure 44). The SDs of the data set and residuals were 0.53 and 0.37, respectively; the difference is significant by the F test (P < .001).

Conclusions: The biologic variation of insulin is a nonrandom process for which the application of SD is not justified. We have shown that by applying a fitted sine function one can predict subsequent values. Since a sine function may be determined by a limited number of points, it would be feasible to compare previous and current sine functions. A change in any of the parameters defining the sine function (mean, amplitude, and period) may indicate a pathologic change before any individual measured value falls outside of the reference range or confidence limits based on SD.

Assessment of Diabetes Management in Long-Term Care Facilities Based on Biochemical Marker

(Poster No. 7)

Rita H. Khoury, MD (rkhoury@aculabs.com); Peter Gudaitis, BS; Bernard P. Salmon, MS; Asha Gandhi, BS; Irina Y. Ryzhkova, BS; Dauna Gudaitis, BS. Aculabs Inc, East Brunswick, NJ.

Context: Diabetes is a chronic illness affecting more than 7% of the US population; this number increases to 20% of individuals in long-term care facilities (LTCF). The first step in diabetes management is glycemic control to prevent and reduce the complication. Hemoglobin A1C is an important factor in the assessment of diabetic control. The American Diabetes Association's recommended goal for A1C is <7%.

Design: Integra800 (Roche Diagnostic, Indianapolis, Ind) was used to measure A1C from 37 294 specimens collected from patients in LTCF (35.3% men and 64.7% women). Patient data were separated into 6 age groups: <50, 51 to 65, 66 to 75, 76 to 85, 86 to 99, and 100 years old. In addition, each group was further separated based on sex. The prevalence of A1C < 7% or ≥8% in each group was calculated.

Results: Patients <50 years old were statistically different from other groups. Sex difference was present up to age 75. More than two thirds of the patients achieved the recommended A1C of <7% (controlled diabetes), and only 14% had A1C of ≥8% (uncontrolled diabetes; Table).

Conclusions: Although diabetes is common in the general geriatric population, based on biochemical indices, this study suggests that diabetes is better monitored in LTCF. Two thirds of the LTCF patients met the recommended goal, compared with only half of the adults with diabetes in the general population. The prevalence of uncontrolled diabetes in LTCF was much less (about half) of what was reported among adults with diabetes, with the "oldest old" having the lowest prevalence.

Retrospective Study Evaluating Existing Routine Laboratory Data to Predict an α-Thalassemia Genotype

(Poster No. 8)

Mohammed Chowdhury, MD (mishraqc@yahoo.com). Department of Clinical Pathology, William Beaumont Hospital, Royal Oak, Mich.

Context: Two-gene deletion α-thalassemia typically results in "thalassemic" red cell indices and is frequently mistaken for iron deficiency, potentially leading to a different investigation and/or inappropriate treatment. The definitive diagnosis of 2-gene deletion α-thalassemia relies upon gene analysis, which is expensive and performed mainly by reference laboratories. The purpose of this study was to investigate the ability of routine laboratory tests to identify 2-gene deletion α-thalassemia and consequently avoid the costly workup for a relatively benign condition. Our hypothesis was that hematologic red cell indices would identify 2-gene deletion α-thalassemia.

Design: A retrospective chart review of all patients for whom gene analysis results were available from 2000 to the present (n = 69) was conducted. Patient data, including age, sex, and various routine laboratory tests, were collected. Data were analyzed using EP evaluator and ROC analysis. Results were obtained for maximum area under the curve, sensitivity, specificity, positive and negative predictive values at various cutoff levels, and P values (at 95% confidence interval).

Results: Based on the statistical analysis, ratio of [(MCV/RBC) +MCH] with cutoff value of 37.0 showed the greatest discriminating power, with 94.1% sensitivity and 80.0% specificity. No patients with a cutoff value >40.0 had 2-gene deletion α-thalassemia.

Conclusions: We propose that if requested, samples from patients with an [(MCV/RBC) + MCH] ratio of <40.0 would be approved for genotyping studies (send-out test), but those with an [(MCV/RBC) + MCH] ratio of >40.0 should be investigated for another cause of abnormal red cell indices.

Human Leukocyte Antigen Class I and Class II Crossmatching Methodologies Reported in College of American Pathologists Surveys From 2002 to 2007: The Increasing Utilization of Flow Cytometry

(Poster No. 9)

Paul J. McGowan, MD1 (mcgowanpj@health.missouri.edu); A. Bradley Eisenbrey, MD, PhD2; Alan Luger, MD.1 1Department of Pathology and Anatomical Sciences, University of Missouri-Columbia; 2Department of Histocompatibility, Gift of Life Michigan, Ann Arbor.

Context: Flow cytometry (FC) has been shown to be the most sensitive method for transplantation crossmatching. The College of American Pathologists (CAP) provides proficiency testing for laboratories that perform transplantation crossmatching. The purpose of this study was to determine if FC has been increasingly incorporated into the repertoire ofmethods used by CAP proficiency testing participants.

Design: We reviewed the following CAP crossmatching surveys: 2002 MX1-A, 2007 MX1-C (MX1-Class I), 2002 MX2-A, and 2007 MX2-C (MX2-Class II). In these surveys, participating laboratories selected the method(s) they used to perform crossmatching. The methods included complement-dependent cytotoxicity-based methods, antihemophilic globulin-augmentation cytotoxicity methods, FC-based methods, and "other" methods. To consolidate the data, we created 3 main method categories. The cytotoxicity methods were combined under "All Direct Cytotoxicity Methods"; antihemophilic globulin-augmentation methods and "other" methods were combined under "Antihemophilic Globulin-Augmentation and All Other Methods"; and FC-based methods were combined under "All Flow Cytometry Methods." The percentage of participants using each method category was calculated for each survey. The differences between the percentage of participants using each method in 2002 and 2007 were calculated (Table).

Results: For the "MX1" crossmatching survey, there was an increase of 7.1% (P = .27) in FC utilization. For the "MX2" survey there was a statistically significant increase of 20.6% (P = .002) in FC utilization.

Conclusions: Based on a review of CAP human leukocyte antigen surveys from 2002 and 2007, FC-based methods are being increasingly incorporated into the milieu of transplantation crossmatchingmethods used by human leukocyte antigen laboratories.

Utility of p53 Immunostaining in Distinguishing Papillary Syncytial Change From Endometrial Glandular Dysplasia in Endometrial Biopsies

(Poster No. 10)

Kristina Borgen, MD1 (krborgen@uic.edu); Carey August, MD.2 1Department of Pathology, University of Illinois at Chicago; 2Department of Pathology, Advocate Illinois Masonic Medical Center, Chicago.

Context: Uterine papillary serous carcinoma (UPSC) and its precursor, serous endometrial intraepithelial carcinoma, are immunoreactive for p53 secondary to nuclear overexpression. Recently, endometrial glandular dysplasia (EGD) has been described as a precursor, with cases similarly demonstrating p53 immunoreactivity. It is important to reliably distinguish EGD from mimics, such as papillary syncytial change (PSC). A recent study of p53 immunoreactivity in EGD included 2 cases of PSC as controls. Our goals were to study p53 immunoreactivity in PSC and to examine its utility in distinguishing PSC and EGD.

Design: We reviewed endometrial biopsies from women whose subsequent hysterectomy specimens showed benign processes.We identified 21 biopsies demonstrating PSC; 5 cases of UPSC served as positive controls. These 26 cases were stained for p53.

Results: In all 5 cases of UPSC, p53 immunostaining was strong in 100% of tumor cells. EGD adjacent to UPSC demonstrated moderate to strong, extensive (but less than 100%) immunoreactivity. In cases of PSC, only 5 demonstrated complete absence of p53 immunostaining. While most of the other 16 cases showed rare, weak positivity, 3 showed scattered cells with moderate immunoreactivity in areas of PSC. In addition, weak to moderate immunoreactivity was observed in non-PSC endometrium, including surface epithelium and exhausted secretory glands.

Conclusions: Because p53 immunoreactivity of moderate intensity may be focally present in PSC and absent in foci of EGD, its utility in distinguishing PSC from EGD in endometrial biopsies is limited. Development of a panel of immunostains is needed to distinguish PSC from EGD in small biopsy fragments.

Utility of PAX-2, a Novel Müllerian Marker, to Differentiate Primary Clear Cell and Serous Papillary Carcinomas of Ovary From Metastatic Renal Cell Carcinoma

(Poster No. 11)

Gloria J. Carter, MD1 (gcarter@mail.magee.edu); Mamatha Chivukula, MD1; Akosua Domfeh, MD1; David J. Dabbs, MD1; Anil Parwani, MD.2 1Department of Pathology, Magee Women's Hospital, Pittsburgh, Pa; 2Department of Pathology, Shadyside Hospital, Pittsburgh, Pa.

Context: Ovarian clear cell carcinoma (OCC) is a distinct histologic subtype of epithelial ovarian cancer, accounting for less than 5% of all ovarian malignancies but having an aggressive clinical course. Distinguishing OCC from metastatic tumors to the ovary with clear cell features can be a diagnostic challenge when clinical examination and imaging studies fail to determine the anatomic site of a primary tumor. PAX-2 belongs to a family of nuclear transcription factors required for development and proliferation of renal tubules. In the female genitourinary tract, PAX-2 expression has been shown in secondary müllerian structures, such as endometriosis and endosalpingiosis, but not on ovarian surface epithelium. Recently, its expression has been demonstrated in papillary serous carcinomas of the ovary.

Design: We assess the use of PAX-2 immunohistochemical stain as a reliable marker for distinguishing primary OCC from metastatic renal cell carcinoma of clear cell type and from serous carcinomas of the ovary. Eleven cases each of OCC and serous carcinomas of the ovary and 7 cases of conventional renal cell carcinoma of clear cell type were retrieved from departmental archives and stained using rabbit polyclonal PAX-2 antibody (Invitrogen, Carlsbad, Calif). A strong nuclear staining is considered positive.

Results: See the Table.

Conclusions: Low or absent expression in cases of ovarian clear cell carcinomas was more common compared with ovarian papillary serous carcinomas. The diffuse, strong nuclear expression is characteristic of renal cell carcinoma, clear cell type and permits separation from ovarian clear cell carcinomas and ovarian papillary serous carcinomas in most cases.

Immature Ovarian Teratoma with Gliomatosis Peritonei and Mediastinal Nodal Gliomatosis

(Poster No. 12)

Yvonne S. Noronha, MD (lynoronha@gmail.com); Ravi Raghavan, MBBS, MD, MRCPath; Kerby C. Oberg, MD, PhD; Craig Zuppan, MD. Department of Pathology, Loma Linda University Medical Center, Loma Linda, Calif.

Mature glial nodules in the peritoneum (gliomatosis peritonei) or intraabdominal lymph nodes (nodal gliomatosis) are rare complications of ovarian teratoma. We report a 13-year-old adolescent girl who presented with a pelvic mass and elevated serum -fetoprotein (29.2 ng/mL). Computed tomography scan demonstrated a 22-cm right ovarian mass with nodular thickening of the omentum and mesentery and a complex cystic lower anterior mediastinal mass. A staged surgical resection was performed. The right ovarian mass was predominantly solid, partly cystic, with sebaceous material, hair, bone, and teeth. Focal immature neuroepithelium was present, which is consistent with grade 2 immature ovarian teratoma, without associated malignant elements. The resection margin was focally involved. Resected omental andmesenteric noduleswere composed entirely of mature glial tissue and reactive fibrosis. The 8.5-cm mediastinal mass consisted of mature neuroglial tissue with focal cystic degeneration and a residual rim of lymphoid tissue (Figure 45). A resected "pulmonary nodule" consisted of lymph node replaced by mature glial tissue. No adjuvant therapy was given. Follow-up computed tomography scan 6 months later showed no evidence of intrathoracic tumor; however, it revealed local bilateral pelvic recurrence, which was treated with chemotherapy. These findings support the concept that nodal gliomatosis, if mature, represents "benign metastasis" and that the pathologic features of the primary tumor are the most important predictor of recurrence. To our knowledge, this is the first reported case in the literature of ovarian immature teratoma with gliomatosis peritonei and thoracic nodal gliomatosis.

The Unusual Cellular Population of the Lamina Propria of the Normal Cervix

(Poster No. 13)

Elaine Kling, MD1 (elainekling@gmail.com); Sumire Kitahara, MD2; Lorena Posligua, MD1; Anais Malpica, MD1; Elvio G. Silva, MD.1 1Department of Pathology, M. D. Anderson Cancer Center, Houston, Tex; 2Department of Pathology, Cedars-Sinai Medical Center, Los Angeles, Calif.

Context: Cervical plasticity has been attributed to the lamina propria, which contains stromal cells (fibroblasts, myofibroblasts, and fibrocytes). Knowing the variable characteristics of these cells is necessary to avoid a misdiagnosis of neoplasia. We evaluated the amount and immunophenotype of these cells and tried to correlate our findings with patients' ages.

Design: We reviewed hematoxylin-eosin slides of 20 cervical cones with dysplasia, 10 cervices from hysterectomies with ovarian borderline tumors/endometriosis, 10 cervices from hysterectomies removed for postpartum bleeding, 10 cervices from hysterectomies removed for vaginal prolapse, and 10 cervices from hysterectomies for endometrial carcinoma (grades 1-2). The following immunohistochemistry was performed: desmin, smooth muscle actin (SMA), calponin, caldesmon, CD34, myogenin, and myoD1.

Results: Calponin, caldesmon, myogenin, and myoD1 were negative in ectocervical and endocervical stromal cells. CD34 was negative in ectocervical stromal cells and 100% positive in endocervical stromal cells (Table).

Conclusions: The endocervix had twice the amount of stromal cells as the ectocervix, regardless of the patient's age. Ectocervical stromal cells were desmin positive and SMA negative; endocervical stromal cells were desmin negative and SMA positive. Of premenopausal patients, those who were postpartum had fewer desmin-positive ectocervical and SMApositive endocervical cells. In postmenopausal patients, desmin-positive ectocervical stromal cells were fewer, with no desmin positivity in prolapse patients. Cells that are desmin positive and negative for SMA, calponin, caldesmon, myogenin, myoD1, and CD34 could represent unusual myofibroblasts and should not be confused with a neoplastic process, especially if a mass is not present. They could be the origin of cellular pseudosarcomatous fibroepithelial stromal polyps and superficial myofibroblastoma.

p16 Expression and its Diagnostic Utility in Uterine and Ovarian Clear Cell Carcinomas

(Poster No. 14)

Kiran R. Vij, MD (kvij@path.wustl.edu); Dengfeng Cao, MD, PhD. Department of Pathology & Immunology, Washington University School of Medicine, St Louis, Mo.

Context: p16 is a cyclin-dependent kinase inhibitor acting as a negative cell cycle regulator. It has been used as a diagnostic marker for serous carcinoma and human papillomavirus-related endocervical adenocarcinoma. However, few data are available regarding p16 expression and its diagnostic utility in uterine and ovarian clear cell carcinomas (CCCs).

Design: Twenty-seven primary uterine and 25 primary ovarian CCCs were included. One paraffin block per case was retrieved for immunohistochemical staining for p16. The staining results were semiquantitatively scored as follows: 0 = <1%, 1+ = 1% to 25%, 2+ = 26% to 50%, 3+ = 51% to 75%, 4+ = 75% tumor cells.

Results: Of the 27 uterine CCCs, 22 (81%) showed p16 expression, 1+ in 3 (11%), 2+ in 2 (7.4%), 3+ in 5 (18%), and 4+ in 12 (44%). Eighteen (72%) of the 25 ovarian CCCs showed p16 expression, 1+ in 6 (24%), 2+ in 2 (8%), 3+ in 4 (16%), and 4+ in 6 (24%). p16 staining in at least 90% of tumor cells was seen in 5 ovarian and 8 uterine CCCs. Two uterine and 2 ovarian CCCs showed p16 staining in 100% of tumor cells.

Conclusions: p16 staining was observed in most uterine and ovarian CCCs. In a significant percentage of cases, staining in 90% to 100% of tumor cells was seen. In female genital tract, diffuse p16 staining is not specific for uterine and ovarian serous carcinoma or human papillomavirus-related endocervical adenocarcinoma. p16 is not a useful diagnostic marker to distinguish uterine CCCs from those of the ovary.

Brenner Tumor With Low Malignant Potential: The Utility of p63

(Poster No. 15)

Xuchen Zhang, MD, PhD (xuchen.zhang@downstate.edu); Janet Schneller, MD; Anthony D. Nicastri, MD. Department of Pathology, The State University of New York, Downstate Medical Center, Brooklyn.

Brenner tumors, which account for 1% to 2% of ovarian tumors, include benign, borderline, and malignant tumors. Borderline Brenner tumor is rare, and accounts for only 3% to 5% of Brenner tumors. Borderline Brenner tumor is subdivided into proliferating Brenner tumor (Brenner tumor with low-grade transitional cell carcinoma [TCC]) and Brenner tumor with low malignant potential (Brenner tumor with high-grade TCC). The difference between malignant and borderline Brenner tumors is the presence of stromal invasion. Stromal invasion, especially microinvasion, is difficult to recognize, which raises concern for misdiagnosis. We report one case of borderline Brenner tumor with low malignant potential. A 53-year-old woman complained of having abdominal pain for 1 month. Computed tomography scan revealed a left adnexal multicystic mass, and the patient underwent total abdominal hysterectomy and bilateral salpingo-oopherectomy. On gross examination, the left ovarian tumor (1900 g; 20 15 11 cm) had a solid component and a multicystic component containing friable papillae. Histologically, the tumor demonstrated both benign Brenner tumor and high-grade papillary TCC components. p63 staining showed strong positivity in both Brenner tumor and TCC components. The p63-positive TCC cells were confined within the basement membrane without stromal invasion. p63 plays a key role in regulating epithelial differentiation and can be used to distinguish between benign and malignant Brenner tumors. Expression of p63 is reported to be confined to benign and borderline Brenner tumors; however, its expression is lost in malignant Benner tumors and ovarian TCC. p63 is a useful marker to differentiate benign, borderline, and malignant Brenner tumors and ovarian TCC.

Hypercoiled Umbilical Cords Are Associated With Small Placentas and Features of Abnormal Perfusion

(Poster No. 16)

Vinay Prasad, MD (vinay.prasad@nationwidechildrens.org); Anna Hughes, MS, PA(ASCP); Emily Chenever, MS, PA(ASCP). Department of Pathology, Nationwide Children's Hospital, Columbus, Ohio.

Context: Hypercoiled umbilical cords are associated with adverse perinatal outcome and fetal demise. Studies have shown a relationship between hypercoiled umbilical cords, hypoxic changes in the placenta, and maturation defects.

Design: The placentas of 25 fetal deaths with hypercoiled cords were examined from fetopsies from between 1998 and 2007. Placentas included those from autopsies (17/25) and surgical specimens (8/25). Gestational ages ranged from 16 to 39 weeks. The placentas were examined and scored for 12 different pathologic changes, including membrane inflammation, cord stricture, inappropriate placental size, significant infarcts, abnormal cord length, hypoperfusion, and presence of associated intrauterine growth restriction. Increase in chorangiosis-like change, fibrioid deposition, and trophoblast knotting was noted.

Results: Significant pathology was seen in 20 of 25 placentas. Maternal inflammatory response was noted in 9 of 25. Seven of 25 were small for gestational age placentas, with 6 of 25 showing multiple infarcts. Seven of 25 showed features of abnormal perfusion; cord strictures were noted in 4 of 25. Other abnormalities included intrauterine growth restriction (3/25), long umbilical cords (2/25), fetal congenital anomalies (4/25), and single umbilical artery (1/25).

Conclusions: Hypercoiled umbilical cords, which can be identified prenatally at ultrasound examination, are associated with placental pathology. Hypercoiled cords are associated with varied pathologic features, including small placentas, intrauterine growth restriction, and abnormal perfusion. This small study strengthens the link between hypercoiled cords and hypoperfusion/maturation defects. Larger studies are necessary to understand the pathophysiology associated with hypercoiled umbilical cords.

Massive Perivillous Fibrin Deposition With Chronic Villitis and Intervillositis: A Rare Combination of Unusual Placental Pathology

(Poster No. 17)

Vinay Prasad, MD (vinay.prasad@nationwidechildrens.org); Emily Chenever, MS, PA; Anna Hughes, MS, PA. Department of Pathology, Nationwide Children's Hospital, Columbus, Ohio.

Massive perivillous fibrin deposition is a rare, poorly understood, and unusual placental finding of uncertain etiology. Massive perivillous fibrin deposition is associated with adverse perinatal outcome, intrauterine growth retardation, and a high rate of recurrence. Chronic intervillositis, an unusual pathologic finding with high risk of recurrence and poor fetal outcome, is characterized by increased mononuclear cells and histiocytes in the intervillous space. Chronic villitis is a common lesion with a high recurrence rate. We report the case of a 30-year-old woman with a 38-week pregnancy. Her history was significant for 2 spontaneous abortions. The infant had intrauterine growth restriction and neurologic abnormalities. The placenta was small (10th percentile), thick, firm, and pale. Microscopic examination showed extensive perivillous fibrinoid encasing villi with foci of avascular villi and intervillous histiocytic and mononuclear infiltrates. Villi with lymphocytic infiltrates associated with avascular villi and perivillous fibrin were noted. CD68 and CD3 confirmed the presence of intervillous histiocytes and villous lymphocytes. There was no evidence of viral cytopathic effect, bacteria, or malarial infection. We report an unusual case of coexisting massive perivillous fibrin deposition, chronic histiocytic intervillositis, and chronic villitis, underscoring the need to look for more than one pathologic process in placentas from patients with a history of recurrent pregnancy loss, intrauterine growth retardation, and inappropriate weight for gestational age placentas. It is critical to identify these lesions for appropriate management and successful pregnancy outcome.

Does Intraoperative Dilation and Curettage Allow for Better Endometrial Evaluation of the Morcellated Uterus?

(Poster No. 18)

Kathryn Klunk, MD1; Damian P. Alagia, MD2; James Robinson, MD2; Elizabeth B. Chahine, MD2; Jamie Shutter, MD3 (jshutter17@hotmail. com). Departments of 1Pathology and 2Obstetrics and Gynecology, George Washington University, Washington, DC; 3Department of Pathology and Cell Biology, University of South Florida, Tampa.

Context: Laparoscopic hysterectomy with uterine morcellation is more frequently being performed. Selected cases are done without preoperative biopsy, and endometrial evaluation may be limited. Currently, there are no studies examining whether intraoperative dilation and curettage (IDC) allows for a more specific diagnosis of the endometrium after morcellation.

Design: We evaluated 21 consecutive cases of morcellated supracervical hysterectomy (MSH) specimens that included an IDC. The indication for hysterectomy in all cases was symptomatic uterine leiomyomas. All specimens were grossed as they would have been had an IDC not accompanied the MSH. In all cases, hematoxylin-eosin-stained sections of the MSH and the IDC were independently reviewed by an expert in gynecological pathology.

Results: Nine (43%) of 21 cases revealed a diagnosis of the endometrium that would not have been identified in the MSH alone. Nine (43%) of 21 cases yielded the same diagnosis of the endometrium. Three (14%) of 21 cases showed a more specific diagnosis in the MSH. Among the 16 premenopausal patients, 9 (56%) yielded a more specific diagnosis by IDC, 5 (31%) showed the same result, and 2 (13%) showed the MSH to be more specific (Table).

Conclusions: Our study indicates that IDC is helpful in endometrial evaluation after uterine morcellation, especially in the premenopausal population. However, not all patients had dysfunctional uterine bleeding. In a premenopausal population with a preoperative diagnosis of dysfunctional uterine bleeding, the yield of IDC prior to MSH may be higher.

Chronic Endometritis: Detailed Clinical and Pathologic Analysis in 105 Patients Diagnosed From 2002 to 2007

(Poster No. 19)

Therese Bocklage, MD1; Matthew A. Smith, BA1 (maasmith@salud. unm.edu); Kori Hagerty, MD1; Betty J. Skipper, PhD.2 Departments of 1Anatomic Pathology and 2Family Medicine, University of New Mexico, Albuquerque.

Context: Chronic plasmacytic endometritis (CPE) is an infectious or reactive process with multiple etiologies. The lesion is reportedly often associated with pelvic inflammatory disease and intermenstrual bleeding. However, the clinical significance of the diagnosis when found incidentally, and whether particular pathologic findings are associated with clinically important CPE, has not been evaluated.We reviewed 105 previously diagnosed chronic endometritis cases and 130 controls to examine the pathologic and clinical correlations in a diverse population.

Design: A pathology database was searched for endometrial biopsies diagnosed as CPE; we found 120 cases. Systematic randomized sampling identified 130 control cases (biopsies not diagnosed as CPE). Slides were carefully reviewed to assess 10 histopathologic features. Clinical records were reviewed for 15 clinical parameters. Analysis was performed using multivariate probability statistics and SAS software (SAS Institute Inc, Cary, NC).

Results: Few patients (3%) received antibiotics or further clinical intervention after the diagnosis of CPE was rendered. The clinical data trended toward less menstrual abnormalities as plasma cells increased. Intensity of inflammation showed no correlation with patient age or symptom duration. Evaluation of controls revealed 17 cases with missed diagnosis of CPE, representing a 13% overall underdiagnosis rate.

Conclusions: In CPE, there are no specific clinical features that correlate with the intensity of pathologic findings. The most specific histologic feature is the presence of plasma cells, and it is predominantly identified in weakly proliferative endometrium. There is a clinically insignificant 13% pathologic underdiagnosis rate. Unlike historically, only a small percentage (4%) of patients had pelvic inflammatory disease.

Extramedullary Hematopoiesis in a Uterine Leiomyoma

(Poster No. 20)

Kevin Kitagawa, MD1 (kevinkit@hawaii.edu); Stacey A. Honda, MD, PhD2; Jane H. Uyehara-Lock, MD.2 1Department of Pathology, University of Hawaii Residency Program, Honolulu; 2Department of Pathology, Kaiser Moanalua Medical Center and University of Hawaii, John A. Burns School of Medicine, Honolulu.

Extramedullary hematopoiesis can be seen in various hematologic disorders; however, isolated hematopoiesis in a benign leiomyoma is extremely rare. The authors present a case of a 42-year-old woman with incidentally discovered hematopoiesis in a leiomyoma removed for heavy menstruation. The patient initially presented to her gynecologist with a complaint of heavy menstrual bleeding for 4 months. She was otherwise asymptomatic. An abdominal ultrasound showed a myomatous uterus. A month later, she returned to her gynecologist for heavy bleeding, and at this time she also had associated fatigue. A complete blood count showed a hemoglobin level of 6.6 g/dL and a hematocrit concentration of 20.5%. She required transfusion of 2 units of packed red cells and underwent uterine myomectomy. Following the surgery, her excessive menstrual bleeding resolved, and her pathologic findings showed a leiomyoma containing clusters of hyperchromatic cells and an increased nuclear to cytoplasmic ratio, predominantly in vascular spaces. Immunostains for various markers revealed that these cells expressed glycophorin A and hemoglobin, indicating that they were immature erythroid precursors. Because of the rarity of this particular entity, the clinical significance of hematopoiesis in a uterine leiomyoma is unclear. Follow-up studies of the patient, including endometrial biopsy, endocervical curettage, abdominal computed tomography scan, and complete blood counts, have all been unremarkable. The patient currently reports feeling well and has resumed normal menses.

D2-40 Expression in Clear Cell Carcinoma of the Ovary and Endometrium

(Poster No. 21)

Debby Rampisela, MD; Kanwaljit S. Aulakh, MD (kaulakh@swmail. sw.org). Department of Pathology, Scott and White Memorial Hospital, Temple, Tex.

Context: D2-40 has been reported to be expressed in lymphatic endothelium and several tumors. The object of this study was to evaluate the expression of D2-40 in primary clear cell carcinoma of the ovary and endometrium.

Design: This study included 19 cases of clear cell carcinoma (12 cases ovarian primary and 7 cases endometrial primary); age of patients ranged from 35 to 70 years; tumor size ranged from 1.3 to 14.5 cm.

Results: Six of 12 cases of clear cell carcinoma of the ovary showed expression of D2-40: 2 were diffusely and strongly positive; 4 were focally and weakly to moderately positive. Two of 7 cases of clear cell carcinoma of the endometrium showed expression of D2-40; both cases were focally and weakly to moderately positive.

Conclusions: Fifty percent of cases with clear cell carcinoma of the ovary and 29% of cases with clear cell carcinoma of the endometrium were positive for D2-40; however, most of the positive cases had only focal positivity. It appears that D2-40 is not significant enough to be used as a diagnostic marker in clear cell carcinoma of the ovary and endometrium.

Immunohistochemical Study of Placental Mesenchymal Dysplasia Associated With Fetal Beckwith-Wiedemann Syndrome

(Poster No. 22)

Blazej Zbytek, MD, PhD (bzbytek@utmem.edu); Jie Zhang, MD. Department of Pathology and Laboratory Medicine, University of Tennessee Health Science Center, Memphis.

Placental mesenchymal dysplasia is a rare condition associated with Beckwith-Wiedemann syndrome (BWS), a disorder related to genes imprinted at the 11p15 region, including the CDKN1C gene. Preferentially maternally expressed, CDKN1C encodes p57Kip2, a cyclin-dependent kinase inhibitor, and negatively regulates cell proliferation. Germline mutations are found in about 50% of familial and 5% of sporadic cases of BWS. We analyzed the expression of p57Kip2, MIB-1, and CD34 in a placenta with mesenchymal dysplasia associated with fetal BWS. A premature male neonate was delivered by cesarean delivery at 24 weeks' gestation to a 21-year-old, G7, P5, L5, A2 mother and died at 6 days of age due to fetal respiratory distress syndrome, sepsis, and stage IV germinal matrix-intraventricular hemorrhage. The postmortem diagnosis of BWS was made on the basis of exomphalos (2.0 cm), large size for gestational age (birth weight of 878 g), macroglossia, visceromegaly, and diffuse cytomegaly of adrenal cortex. The associated placenta was stained by p57Kip2, MIB-1, and CD34 antibodies. The placenta was large and heavy (462 g) for gestation stage and showed aneurysmal vascular dilatation in stem and intermediate villi, stromal cell hyperplasia, and hydropic villi. No cistern or trophoblastic proliferation was found. Cytotrophoblastic and mesenchymal cells in villi were negative for p57Kip2 but were positive for MIB-1. A CD34 antibody decorated the abundant vascular endothelial cells in the villi. The lack of p57Kip2 expression in a placenta with mesenchymal dysplasia implies an imprinted maternal CDKN1C gene that results in the proliferation of cytotrophoblast and mesenchymal cells.

Prevalence of Sexually Transmitted Diseases and Rate of Coinfection: A Study of 10 114 Females From a University-Based Healthcare System

(Poster No. 23)

Zhuang Zuo, MD, PhD; Javier A. Laurini, MD (jlaurini@usouthal.edu); Elliot J. Carter, MD. Department of Pathology, University of South Alabama, Mobile.

Context: A recent survey by the Centers for Disease Control and Prevention revealed an alarming infection rate for sexually transmitted diseases (STDs), with approximately 25% of teenaged girls having at least one infection. This study was designed to investigate the prevalence of STDs among patients from our university-based obstetrics and gynecologic clinics.

Design: A search of our laboratory information system revealed 10 114 female patients in whom at least one STD was identified during the period from May 2004 to May 2007. Accrued data from the laboratory information system included patient demographics and test results for the following infectious agents: human papillomavirus (HPV), Chlamydia trachomatis, Neisseria gonorrhoeae, human immunodeficiency virus, hepatitis B virus, and hepatitis C virus.

Results: One thousand eight hundred nineteen patients (17.98%) tested positive for at least one STD, with the most common infections being HPV (31.17%), C trachomatis (10.64%), hepatitis C (9.88%), and N gonorrhoeae (3.34%). Coinfection with HPV and C trachomatis was seen in 10.10% of the patients. Significantly higher infection rates for HPV (63.75%) and C trachomatis (20.38%) were observed in 10- to 20-year-old patients. The current study included a small group of 17 patients who were older than 80 years. This particular group showed a surprising HPV infection rate of 23.53%, suggesting a bimodal age distribution for STDs.

Conclusions: This study confirmed the alarmingly high rate of STD infection in females, especially in the 10- to 20-year-old group. Given the high rates of coinfection, the presence of one STD, especially HPV, should prompt further testing to identify other pathogens requiring additional treatment and follow-up.

Struma Ovarii With a Focus of Medullary Thyroid Carcinoma

(Poster No. 24)

Rashmi K. Shamanna, MD (rshaman1@hfhs.org); Min W. Lee, MD; Arthur R. Gaba, MD. Department of Pathology and LaboratoryMedicine, Henry Ford Hospital, Detroit, Mich.

Struma ovarii is a monodermal variant of ovarian teratoma with predominant thyroid tissue. Thyroid carcinomas arising in struma include papillary, follicular, and insular variants. Medullary carcinoma has not been reported. A 56-year-old woman undergoing treatment for hepatocellular carcinoma had an incidental pelvic mass on imaging. A computed tomography scan of the pelvis demonstrated an enhancing complex cystic ovarian mass. The patient had high serum levels of CA 125, carcinoembryonic antigen, -fetoprotein, and normal calcitonin. She underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy. Grossly, the left ovary revealed a 11.1 6.0 4.5-cm multicystic mass with smooth inner lining. Cysts were mostly filled with clear serous fluid and some gelatinous material. Microscopic sections demonstrated struma ovarii with a central 5-mm nodule of medullary thyroid carcinoma composed of polygonal cells forming nests and cords. Cells had eosinophilic cytoplasms, pleomorphic nuclei with intranuclear inclusions, and numerous mitoses. The nodule showed positive immunostaining for calcitonin, synaptophysin, chromogranin, and somatostatin. It was negative for thyroglobulin, TTF-1, and monoclonal carcinoembryonic antigen. Two months after surgery, follow-up investigations revealed persistent serum elevation of CA 125 and carcinoembryonic antigen. Serum calcitonin remained normal. Thyroid ultrasound showed an equivocal nodular area within the left lobe, which was benign on aspiration cytology. The patient had total follow-up at 5 months without recurrence or possible primary disease. To our knowledge, this is the first reported case of medullary thyroid carcinoma arising within struma ovarii. Presence of malignancy within struma warrants appropriate management and monitoring. The importance of careful gross examination and extensive sampling cannot be overemphasized (Figure 46; H&E, hematoxylin-eosin; LP, low power; and HP, high power).

Effect of Conjunctive Interpretation of p16 Immunostains on Accuracy and Interobserver Agreement for Diagnosing CIN 2 Positive on Hematoxylin-Eosin Slides

(Poster No. 25)

Ruediger Ridder, PhD1 (ridder@mtmlabs.com); Marcus J. Trunk, MD1; Christine Bergeron, MD2; Jaume Ordi, MD3; Dietmar Schmidt, MD.4 1Department of Research & Development, mtm laboratories, Heidelberg, Germany; 2Department of Pathology, Laboratoire Pasteur-Cerba, Cergy, France; 3Department of Pathology, Hospital Clinic, Barcelona, Spain; 4Department of Gynecopathology, Institute of Pathology, Mannheim, Germany.

Context: Overexpression of p16 has been demonstrated in dysplastic cervical lesions and has been closely linked at the molecular level to the activity of HR-HPV E7 oncoproteins in transforming infections. We investigated the effect of the conjunctive interpretation of slides immunostained for p16 together with hematoxylin-eosin (H&E)-stained slides on diagnostic accuracy and agreement between pathologists.

Design: A European study was performed on 500 cervical tissue specimens. H&E-based consensus diagnosis of expert gynecopathologists served as the gold standard. Twelve European panel pathologists established individual diagnoses for all cases on H&E alone. In a second assessment round, the same slides were used to establish a diagnosis conjunctively on H&E and p16 immunohistochemistry slides.

Results: Sensitivity for identification of CIN 2+ in cervical biopsies was improved from 77% for H&E slides to 87% by adding p16-stained slides. The conjunctive use of p16-stained slides reduced the number of falsenegative results by almost 50%. Furthermore, the interrater reliability between panel pathologists for diagnosing CIN 2+ was significantly improved. A correlation between the individual pathologist's rating of p16 staining patterns and changed diagnosis compared with H&E alone revealed that almost all cases with upgrades to CIN 2+ showed a diffusely positive p16 staining pattern. In contrast, cases downgraded to either negative for dysplasia or CIN 1 showed positive or negative p16 staining patterns at comparable numbers, indicating that a positive p16 staining pattern per se did not overrule morphology interpretation.

Conclusions: The conjunctive use of slides immunostained for p16 significantly increases diagnostic accuracy and interobserver agreement for the identification of CIN 2+ lesions in cervical biopsies.

Financial Disclosure: Dr Ridder owns stock in mtm laboratories.

Placental Cryptococcosis

(Poster No. 26)

Angela D. Darko, MD (adark001@umaryland.edu); Chen-Chih Sun, MD; Daniel Dim, MD. Department of Pathology, University of Maryland Medical Center, Baltimore.

We present a case of placental cryptococcosis in a 20-year-old woman, gravida 1, para 1. The patient had a history of congenital and multidrugresistant HIV/AIDS, with a viral load of 49 885, and a CD4 count of 14. She had been treated for Cryptococcus neoformans meningitis/cryptococcemia 5 months prior to delivery. Cesarean delivery was performed at 37 weeks of gestation with delivery of a single full-term male with Apgar score of 8 and 9. Mother and newborn did not have any complications and were discharged on the third day after delivery. There was no evidence of Cryptococcus infection in the newborn. The placenta grossly showed multiple white nodules. Microscopically, numerous encapsulated budding yeasts, morphologically consistent with Cryptococcus, were identified in the intervillous space and occasional chorionic villi with no evidence of inflammatory response. In the age of HIV/AIDS, Cryptococcus opportunistic infections are not uncommon. However, the unique clinical and pathologic findings in placenta Cryptococcus and neonatal transmission are rare and not well defined. Only 2 cases of placental cryptococcosis have been reported in the medical literature, and our case is the second report demonstrating pathologic evidence of Cryptococcus in the placenta.

Epithelioid Smooth Muscle Tumor of the Ovary With Rhabdoid Features

(Poster No. 27)

Christopher N. Thompson, MD (cthompson@swmail.sw.org); Debby Rampisela, MD. Department of Pathology, Scott and White Memorial Hospital, Temple, Tex.

Smooth muscle tumors of the ovary are rare. We report a case of an asymptomatic 43-year-old woman who was discovered to have a pelvic mass at her yearly gynecologic exam. Subsequent magnetic resonance imaging and ultrasound imaging showed a complex pelvic mass, which was resected. On gross examination, a 3.3 2.5-cm mostly homogeneous, pale tan, rubbery, well-circumscribed mass with foci of hemorrhage was identified in the left ovary. Microscopic sections of the tumor demonstrated a diffuse proliferation of epithelioid cells admixed with hyalinized areas. The epithelioid cells were mildly to moderately pleomorphic and had vacuolated, clear to eosinophilic cytoplasm and prominent nucleoli. Some cells had eosinophilic cytoplasmic globules with peripheral nuclei, suggestive of rhabdoid morphology. There was no necrosis. The tumor was positive for desmin, smooth muscle actin, muscle-specific actin, and caldesmon. It was negative for inhibin, calretinin, cytokeratin (CK) MNF 116, CK7, CK20, epithelial membrane antigen, myogenin, and c-kit. Ki-67 and histone H3 stains indicated a low proliferative index. This staining profile is most consistent with a smooth muscle origin. To our knowledge, an ovarian epithelioid smooth muscle tumor with rhabdoid features has not been previously reported in the literature.

Utility of p57 Immunostain in Conjunction With Fluorescence In Situ Hybridization Analysis for Diagnosing Complete Hydatidiform Mole, Partial Hydatidiform Mole, and Hydropic Abortions: A Study of 29 Cases

(Poster No. 28)

Jing Liu, MD, PhD (missjackie52004@yahoo.com); Jacqueline T. Nguyen, DO; Michael Covinsky, MD. Department of Pathology, University of Texas-Houston Health Science Center, Houston.

Context: Interobserver and intraobserver variability is problematic in diagnosing early complete mole (e-CM), partial mole (PM), and hydropic abortion (HA) due to overlapping histologic findings. Although immunostaining for p57 has been proposed in the past, it is not widely accepted due to difficulty in interpreting stained sections.

Design: Twenty-nine cases of products of conception were retrieved. Original diagnoses included 11 e-CMs, 5 PMs, and 13 HAs. Immunostaining with p57 monoclonal antibody was performed on formalin-fixed tissue sections from each case. The final diagnoses were based on hematoxylineosin, fluorescence in situ hybridization analysis, and clinical correlation. Only distinct nuclear staining in cytotrophoblasts and mesenchymal cells in villi was recorded as positive. The intervillous trophoblasts and decidual cells served as internal controls.

Results: p57 was negative in 9 of 11 e-CMs and positive in 12 of 13 HAs and 2 of 5 PMs. Fluorescence in situ hybridization analysis performed on cases with unexpected immunostaining findings led to reclassification: of 2 p57+ e-CMs, one was an HA, and the other was a PM; all 3 p57- PMs were e-CMs; and the p57^sup -^ HA was an e-CM. Positive cases showed 10% of villous cells stained. Two e-CMs expressed p57 in <2% of villous cells, which was considered negative. A few positively stained cells most likely represented intervillous trophoblasts overlapped with villous tissue.

Conclusions: p57 immunostaining is useful for distinguishing between e-CM, PM, and HA. Familiarity of true-positive staining pattern is crucial. Using p57 immunostaining in evaluation of hydropic villi can yield a definitive diagnosis of e-CM and avoid unnecessary fluorescence in situ hybridization analysis. Fluorescence in situ hybridization analysis is necessary only in cases with unexpected p57 results.

Bacteremia Caused by Paenibacillus popilliae in a Patient on Hemodialysis

(Poster No. 29)

Jie Ouyang, MD, PhD (jie.ouyang@downstate.edu);Matthew R. Pincus, MD, PhD. Department of Pathology, The State University of New York, Downstate Medical Center, Brooklyn.

Formerly known as Bacillus popilliae, Paenibacillus popilliae (P popilliae) was reclassified as Paenibacillus genus because of unique phenotypic characteristics and comparative 16S rRNA sequence. Definitive identification of this bacillus can be performed using a highly specific gene probe to a unique nucleotide sequence in the 16S rRNA of this organism. Only one human infection by P popilliae has been reported to date. We now report the second case of infection by P popilliae in a patient, which was most likely caused by an indwelling hemodialysis catheter that resulted in bacteremia. This is the first case reported in which the organism of P popilliae is identified by 16S rRNA sequencing in human infection. We performed the sequencing of the 16S rRNA gene on the clinical isolate (BKBLC2156 clone), and the result was closely related to the P popilliae-type strain on the phylogenetic tree. Pairwise comparisons showed 99.23% (1422/1433 overlapping positions) sequence identity between the P popilliae-type strain (access number AF071859) and the BKBLC2156 clone. This degree of similarity is often seen between strains within the same species. This organism was found to be susceptible to all of the commonly used antibiotics, and the patient recovered rapidly after antibiotic treatment. This constitutes the second reported case of human infection and sepsis by P popilliae. It is also the first reported case of human infection by Paenibacillus spp in a hemodialysis patient.

Do We Need to Culture Every Pleural Fluid?

(Poster No. 30)

Eugene S. Pearlman, MD (czaroflabs@aol.com); Melissa Haygood, MT(ASCP); Stanley Sprei, MD. Department of Pathology, Lourdes Hospital, Paducah, Ky.

Context: The marketing of automated instruments that rapidly generate white cell counts on serous body fluid specimens raises the question of whether such data are useful for screening such fluids when culture is ordered; in some cases, we may be able to reduce workload in the microbiology laboratory.

Design: Prior to obtaining new hematology analyzers, we tested this question by reviewing pleural fluid specimens submitted for manual white cell counts and culture in the years 2000 to 2003 inclusive (training set) and between January 1, 2004, and June 30, 2007 (test set).

Results: The training set included 194 specimens (191 patients) and 6 positive bacterial cultures. Neither training nor test sets contained positive fungal or mycobacterial cultures. A 25% stratified random sampling suggested a total of 472 (95% CI, 394-540) preculture events (Gram stain, acid-fast bacilli smear, and potassium hydroxide preparation) and 668 (95% CI, 588-768) culture events (aerobic, anaerobic, mycobacterial, and fungal) in the training set. A rule that reserved culture for those specimens with an absolute neutrophil count of ≥100/µL and a relative neutrophil count of ≥50% detected all culture-positive specimens and reduced workload by approximately 85%. We applied this rule to the test set, which contained 160 specimens (151 patients) with 5 positive bacterial cultures. Again, we achieved 100% sensitivity with an estimatedworkload reduction of 85%.

Conclusions: Our data suggest that the development of rules from white cell count data to screen serous fluids for culture may be feasible, although such rules will probably vary with the fluid and between institutions serving different populations.

Esophageal Tuberculosis: A Rare Presentation in an Immunocompetent Patient

(Poster No. 31)

Deborah A. Cook, MD1 (deb≥or≥ah@hotmail.com); Laura W. Lamps, MD2; Phillip E. Ferguson, MD.3 1Department of Pathology at St Bernards Regional Medical Center, Ross University School of Medicine, Jonesboro, Ark; 2Department of Pathology, Univeristy of Arkansas for Medical Sciences, Little Rock; 3Department of Pathology, Doctors' Anatomic Pathology Services, Jonesboro, Ark.

The involvement of the esophagus with tuberculosis is uncommon and extremely rare in patients without human immunodeficiency virus or other immunosuppressive conditions. We report a case of esophageal tuberculosis as the initial finding of infection in an immunocompetent male complaining of dysphagia. Endoscopic exam revealed a 5-cm stricture, which was biopsied. Histology showed caseating granulomas (Figure 47), and acid-fast bacillus stains were positive for acid-fast bacilli. Subsequent polymerase chain reaction analysis was positive for Mycobacterium tuberculosis species. A PubMed search identified fewer than 10 case reports of esophageal tuberculosis in immunocompetent patients as the initial diagnostic finding. Nonspecific clinical signs, such as weight loss, fever, and dysphagia, can cause esophageal tuberculosis to be confused with carcinoma when found in such a rare location. While uncommon, tuberculosis can present with unusual findings and in unusual locations. Pathologists and clinicians should maintain vigilance in considering tuberculosis in their differential diagnosis.

Actinomycosis Masquerading as Malignancy: An Analysis of 16 Cases

(Poster No. 32)

Sara Shalin, MD1 (sc042768@bcm.tmc.edu); Bhuvaneswari Krishnan, MD.1,2 1Department of Pathology, Baylor College of Medicine, Houston, Tex; 2Michael E. DeBakey VA Medical Center, Houston, Tex.

Context: Actinomyces are normal flora of the oral, vaginal, and gastrointestinal tract. Actinomycosis, while rare, has been the subject ofmultiple case reports, particularly as a mimicker of malignancy. However, a systematic study of multiple cases has not been performed.

Design: Twenty-two cases of actinomycosis diagnosed at our institution from 1998 to 2007 were identified. Six cases showed actinomyces in the ulcer bed in various locations without invasion. These were excluded, resulting in 16 cases of actinomycosis. The clinical information and pathologic findings were then reviewed.

Results: There were 15 men and 1 woman with an age range of 36 to 75 years. The sites of involvement and clinical findings of 16 cases are shown in the Table. Eight cases were clinically thought to be carcinoma or lymphoma. Two histologic patterns were seen: abscess with prominent microcolonies of bacteria (12 cases) and dense fibrous reaction with chronic inflammation and rare entrapped microcolonies (4 cases). In the second pattern, microbiologic cultures were not helpful, and patients required multiple biopsies for a diagnosis.

Conclusions: Actinomycosis can masquerade as carcinoma or lymphoma. The diagnosis in cases with intense fibrous reaction was difficult, requiring a high index of suspicion and reexamination of multiple levels, since microbiologic cultures were not helpful. Many microcolonies are seen with abscess formation.

Utility of a Histoplasma capsulatum Enzyme Immunoassay for Diagnosis of Disseminated Histoplasmosis and Correlation With Disease Activity

(Poster No. 33)

Michelle Cox, MD (coxronim@uams.edu); Gina Pesek, MD; Dan C. Phan, MD, PhD; Gail Woods, MD. Department of Pathology, University of Arkansas for Medical Sciences, Little Rock.

Context: Infection with Histoplasma capsulatum is often asymptomatic but has considerable morbidity and mortality in the immunocompromised population. Rapid diagnosis is essential in this susceptible population. The goal of this study was to evaluate the accuracy of a newly developed commercial enzyme immunoassay (EIA) for detection of H capsulatum antigen in urine (Immuno-Mycologics, Norman, Okla) for diagnosis of disseminated histoplasmosis.

Design: Adult patients with suspected histoplasmosis were enrolled between August 2006 and August 2007. All patients had a urine histoplasma antigen EIA performed. Additionally, a specimen collected within 72 hours of the urine sample was submitted for fungal culture and/or histopathologic or cytologic examination. EIA tests results were interpreted as follows: negative (<2 EIU), indeterminate (2.0-4.0), and positive (>4.0). Final diagnosis was based on culture and/or histologic studies. Treatment and outcome were also reviewed.

Results: Of the 177 patients in the study, 6 were diagnosed with disseminated histoplasmosis. Five of the 6 had a positive histoplasma blood culture (2 of these also had positive histopathology or cytopathology); 1 had a positive bronchoalveolar lavage culture. All 6 had a positive urine histoplasma antigen test (sensitivity, 100%). Two patients without histoplasmosis had a positive urine antigen (specificity, 99%).

Conclusions: The Immuno-Mycologics urine histoplasma antigen EIA is a rapid and reliable method of diagnosing disseminated histoplasmosis. With early diagnosis, rapid initiation of therapy can reducemorbidity and mortality in the immunocompromised population. A limitation of our study is the small number of patients with disseminated histoplasmosis. Further assessment of this EIA is needed to confirm our results.

Admission Screening for Methicillin-Resistant Staphylococcus aureus (MRSA) and Subsequent Patient Triage: Data From the Durham Veterans Affairs Medical Center "MRSA Initiative" and Comparison With Historical Institutional Epidemiologic Data

(Poster No. 34)

John M. Childs,MD1 (john.childs@duke.edu); Kenneth H.Wilson,MD2; Dolph Klein, PhD2; Emile El-Shammaa, MD3; Susan B.Wilkins, BS2;Maria J. Joyce, MD, DTM&H.2 1Department of Pathology, Duke UniversityMedical Center, Durham, NC; 2Department of Infectious Disease, Veterans Affairs Medical Center, Durham, NC; 3Department of Emergency Medicine, Ohio State University College of Medicine, Columbus.

Context: Methicillin-resistant Staphylococcus aureus (MRSA) is an important cause of nosocomial infections. We are reporting observations from the Durham Veterans Affairs Medical Center "MRSA Initiative." The initiative includes MRSA screening with a 2-hour turnaround time on all admissions/transfers, patient triage based on MRSA status, and discharge testing for patients initially screened as negative. Comparisons will be made to institutional epidemiologic data collected during 1992 to 1993.

Design: One thousand seven hundred seventy-five patients (95% of admissions between October 2007 and January 2008) were screened for nasal MRSA colonization by polymerase chain reaction-based testing using the Genexpert (Cepheid, Sunnyvale, Calif). MRSA-positive patients were immediately placed in contact isolation on admission. MRSA-negative patients were retested on discharge by culture.

Results: Hospital-wide MRSA colonization and in-hospital acquisition rates were 10.4% and 1.26%, respectively. For combined medical/surgical floors, the rates were 9.2% and 1.82%, respectively. MRSA colonization and acquisition rates from 6 months during 1992 to 1993 assayed by culture for patients admitted to a medical/surgical floor were 5.6% and 3.6%, respectively.

Conclusions: The MRSA colonization rate on admission has increased compared with institutional data from 1992 to 1993. Despite a higher admission colonization rate, the in-hospital acquisition rate has decreased, likely due to heightened infection control awareness and current patient triage strategies. The benefit of the "MRSA Initiative" in decreasing hospital-acquired infections is still unknown.

Fungal Infections Mimicking Neoplasm: A Report of 2 Cases

(Poster No. 35)

Kevin L. Tyler, DO (ktyler@usd.edu); Ali D. Jassim, MD, PhD. Department of Pathology, Sanford School of Medicine of the University of South Dakota, Sioux Falls.

Histoplasma capsulatum and Blastomyces dermatitidis are both dimorphic fungi regionally endemic in the Midwestern United States and have been reported to cause unusual manifestations of disease. Recognition of fungal-induced histopathologic changes mimicking neoplasm is of practical significance. Two cases originally diagnosed as neoplastic are presented. Case 1 is a 59-year-old man with a right adrenal mass. Adrenalectomy was performed and revealed an enlarged adrenal gland with a 1.5-cm mass. Histologically, the lesion revealed atypical cortical hyperplasia and central necrosis with subsequent diagnosis of adrenal cortical tumor. Case 2 is a 53-year-old man with a large perianal lesion thought to be verrucous carcinoma. The perianal excision was sampled for frozen sectioning with a subsequent diagnosis of squamous cell carcinoma. Cases 1 and 2 were both referred for pathologic consultation. In case 1, immunohistochemical stains for MIB-1, Melan-A, and inhibin, as well as for Gomori methenamine-silver and periodic acid-Schiff, were performed. The former stains were negative, whereas latter stains revealed numerous fungal organisms consistent with Histoplasma species. Case 2 demonstrated florid pseudoepitheliomatous hyperplasia with a focal granulomatous response. Subsequent Gomori methenamine-silver and periodic acid-Schiff stains revealed thick-walled, broad-based organisms consistent with cutaneous blastomycosis. Certain fungal infections can cause marked atypia and can be easily misdiagnosed as neoplastic if the index for suspicion of fungal infection is not high. Diagnosis includes assessment of background inflammation with subsequent histochemical staining with Gomori methenamine-silver or periodic acid-Schiff. The accurate diagnosis of fungal organisms is imperative for appropriate treatment.

Ochrobactrum anthropi Bacteremia in a Patient Treated With Intravenous Treprostinil for Pulmonary Hypertension

(Poster No. 36)

Bethany J. Tierno, MD1 (bethany.tierno@bmc.org); Paschalis Vergidis, MD2; Jason Konter, MD3; Harrison W. Farber, MD3; Nancy S. Miller, MD.1 Departments of 1Pathology and Laboratory Medicine, 2Infectious Disease, and 3Pulmonary Medicine, Boston Medical Center, Boston, Mass.

Recently, the Centers for Disease Control and Prevention reported an increase in overall and gram-negative bloodstream infections in patients receiving intravenous (IV) treprostinil for pulmonary arterial hypertension as compared with those on IV epoprostenol. We present a previously unreported case of Ochrobactrum anthropi bacteremia in a patient on IV treprostinil. Ochrobactrum anthropi is an aerobic, gram-negative, nonfermenting bacillus infrequently associated with local or systemic infection, mostly in immunocompromised hosts. Clinical significance includes its typical inherent resistance to penicillins, aztreonam, and most cephalosporins due to an AmpC β-lactamase. A 63-year-old woman with pulmonary arterial hypertension receiving IV treprostinil via indwelling venous catheter was admitted to our hospital after blood cultures drawn as an outpatient grew gram-negative rods. She had a recent history of urinary tract infection treated empirically with ciprofloxacin. Upon admission, empiric ceftriaxone therapy was initiated. Repeat blood cultures remained positive for a gram-negative rod, and therapy was changed to cefepime. Transthoracic echocardiogram showed normal cardiac valves without vegetations. The gram-negative rod was identified as O anthropi, and imipenem therapy was started. Persistent bacteremia eventually resolved after removal of the indwelling venous catheter. The patient was bacteremic for a total of 11 hospitalization days with 16 sets of blood cultures positive for O anthropi. Awareness of common and esoteric gramnegative infections in patients on IV treprostinil is important. Given their innate antimicrobial resistance, organisms like O anthropi may challenge empiric therapeutic considerations.

Empyema Necessitatis Due to Methicillin-Resistant Staphylococcus aureus: A Case Report and Review of the Literature

(Poster No. 37)

Kelly N. Mizell, MD (kmizell@usouthal.edu); Kimberley V. Patterson, MD; J. Elliot Carter, MD. Department of Pathology, University of South Alabama, Mobile.

Empyema necessitatis is a rare complication of empyema in which the pleural infection spreads outside of the pleural space to involve the soft tissues of the chest wall. Most cases of empyema necessitatis are related to Mycobacterium tuberculosis and less commonly to Actinomyces spp and Streptococcus spp. Staphylococcus aureus has rarely been reported as the causative agent of empyema necessitatis, with most of the isolates being methicillin sensitive. Only rare cases of empyema necessitatis due tomethicillin-resistant S aureus have been reported in the medical literature. We report the case of a 59-year-old white man who presented to our institution with complaints of pain and swelling in his left upper chest of 2 months' duration. A computed tomography scan of the chest showed an 8.1 × 6.5-cm lesion that extended from the left upper lobe of the lung into the extrathoracic soft tissues beneath the left upper pectoralismuscle. A wedge resection of the left upper lung lobe revealed lung tissue with an organizing pneumonia-like pattern associated with marked acute pleuritis. Blood and urine cultures and cultures of the left chest soft tissue mass grew methicillin-resistant S aureus. The patient was successfully treated with vancomycin followed by a 10-day outpatient course of ciprofloxacin and trimethoprim-sulfamethoxazole. This case represents an extremely rare manifestation of an increasingly dangerous bacterial pathogen.

Analysis of ProEx-C Expression in Pulmonary Neuroendocrine Tumors: Potential Target for Therapy

(Poster No. 38)

Hema Khurana, MD1 (hkhurana@tmhs.org); Timothy C. Allen, MD2; Jim Zhai, MD1; Anna Sienko, MD1; Roberto Barrios, MD1; Abida Haque, MD1; Philip T. Cagle, MD.1 1Department of Pathology, TheMethodistHospital, Houston, Tex; 2Department of Pathology, University of Texas, Tyler.

Context: Primary pulmonary neuroendocrine tumors (PNTs) are classified into 3 major types: carcinoid, large cell neuroendocrine carcinoma (LCNC), and small cell carcinoma (SCLC). The 5-year survival rate for LCNC and SCLC remains dismal. New therapies are needed for these aggressive forms of PNT. The ProEx-C immunocytochemical assay utilizes a cocktail of monoclonal antibodies directed against proteins associated with aberrant S-phase cell cycle induction (topoisomerase IIA, minichromosome maintenance protein 2). We evaluated the immunohistochemical expression of ProEx-C in PNT.

Design: Tissue microarrays containing triplicate punch samples of 66 PNTs (25 carcinoids, 31 SCLCs, and 10 LCNCs) were utilized. Immunohistochemical stain with ProEx-C (prediluted; TriPath Imaging Inc, Burlington, NC) was performed. For each sample, the percentage of tumor cells staining was recorded on a scale from 0 to 3. Immunopositivity in tumor cells was graded on a scale from 0 to 3 and averaged for the 3 punches from each tumor. Average score of 0 or 1 was classified as weak expression, whereas average score of 2 or 3 was classified as strong expression.

Results: Intense nuclear staining was detected in 10 (100%) of 10 LCNCs, 30 (96.7%) of 31 SCLCs, and 2 (8%) of 25 carcinoid tumors.

Conclusions: The ProEx-C expression in LCNC and SCLC was significantly higher than in the carcinoid tumors. This suggests that overexpresssion of ProEx-C may have a role in the aggressive behavior of LCNC and SCLC. Pharmacologic manipulation of the S-phase proteins included in ProEx-C may provide a novel therapeutic approach for the treatment of SCLC and LCNC.

Primary Pulmonary Monophasic Fibrous Synovial Sarcoma With Light Microscopic and Ultrastructural Features of Malignant Peripheral Nerve Sheath Tumor

(Poster No. 39)

Suzanne H. Martin, MD (smartin@usouthal.edu); J. Allan Tucker, MD; Kimberley V. Patterson, MD. Department of Pathology, University of South Alabama, Mobile.

Synovial sarcoma arising primarily in the lung is an exceedingly rare occurrence with few reported cases in the literature. Diagnosis of monophasic fibrous synovial sarcoma at this site is complicated by its rarity and histologic similarity to other more commonly occurring pulmonary sarcomas. The diagnosis has usually been based primarily on the presence of the reciprocal (x;18) translocation or gene fusion product, with supporting light microscopic morphology. We report the case of a primary pulmonary monophasic fibrous synovial sarcoma in which light microscopic and ultrastructural features suggested schwannian differentiation. A 22-year-old man presented with shortness of breath and hemoptysis. Computed tomography scan showed a 14 × 11-cm left upper lobe lung mass; left pneumonectomy revealed an 11-cm mass with focal hemorrhage and cystic change. Hematoxylin-eosin-stained sections showed a high-grade spindle cell neoplasm without epithelioid component. Features suggestive of peripheral nerve sheath differentiation included prominent nuclear pallisading, Verocay bodies, and transmission electronmicroscopic demonstration of elongated interdigitating cytoplasmic processes and flocculent external lamina-like material. Neoplastic cells were focally positive for neuron-specific enolase and synaptophysin and negative for CAM 5.2, S100, desmin, cytokeratin 7, and chromogranin. Isolated positivity for epithelial membrane antigen was observed. Reverse transcriptase-polymerization chain reaction revealed the SYT/SSX2 fusion product. This case is an example of an extremely rare primary lung sarcoma, and it illustrates the importance of using cytogenetic data in the diagnosis of sarcomas, especially where overlapping features may point to alternative diagnoses.

Malignant Pulmonary Neoplasms With Mesenchymal Differentiation: A Review of 64 Cases From One Institution

(Poster No. 40)

Pablo W. Gomez, MD (pwgomez@tmhs.org); Philip T. Cagle, MD; Jim Q. Zhai, MD. Department of Pathology, Weill College of Medicine Cornell University, The Methodist Hospital, Houston, Tex.

Context: Primary malignant mesenchymal neoplasms of the lung (MMNL) are extremely rare and include monophasic and biphasic tumors. We investigated our archives to determine the types of MMNL, their relative frequencies as primary (P) versus metastatic (M) tumors and their clinicopathologic features.

Design: A search of surgical pathology files at The Methodist Hospital, Houston, Tex, from January 1980 to August 2007 identified 64 patients with pulmonary neoplasms with at least a focal malignant mesenchymal component. Specimens included 2 core-needle biopsies, 8 transbronchial biopsies, 13 unspecified biopsies, 2 fine-needle aspirations, 16 lobectomies, 20 wedge resections, and 3 pneumonectomies.

Results: The male to female ratio was 34:29. The average age at diagnosis was 58.9 years (range, 10-82 years). Seventy-two percent of P tumors fell into 2 diagnostic categories: sarcomatoid carcinomas (55%) and Kaposi sarcoma (17%). Sixty-nine percent of M tumors fell into 3 diagnostic categories: sarcomatoid carcinomas (26%), high-grade sarcomas/malignant fibrous histiocytoma (23%), and leiomyosarcomas (20%). Diagnosis from most to least common was as follows: sarcomatoid carcinomas (9 M, 16 P), high-grade sarcoma/malignant fibrous histiocytoma (8 M, 1 P), leiomyosarcomas (7 M, 2 P), Kaposi sarcomas (5 P), alveolar soft part sarcomas (3 M), angiosarcomas (2 M, 1 P), chondrosarcomas (2 M), osteogenic sarcomas (2 M), fibrosarcomas (1 M, 1 P), rhabdomyosarcomas (1 M, 1 P), Ewing sarcoma (1 P), sarcoma not otherwise specified (1 P).

Conclusions: The most frequent primary MMNL are sarcomatoid carcinomas and Kaposi sarcoma, and the most frequent metastatic MMNL are sarcomatoid carcinomas, high-grade sarcomas/malignant fibrous histiocytoma, and leiomyosarcomas.

A Rare Case of Amyloidoma in Thymus

(Poster No. 41)

Zohreh Eslami, MD, PhD1 (zeslami40@hotmail.com); Elias Abdulnour, MD2; Gilles Gariepy, MD.1 Departments of 1Pathology and 2Thoracic Surgery, Centre Hospitalier Universitaire de Montre al, Saint-Luc Hospital, Montreal, Que bec, Canada.

We present a case of localized tumorlike amyloidosis of the thymus. A 53-year-old woman was admitted with a diagnosis of calcifiedmediastinal tumor based on chest x-ray examination and chest computed tomography scan. Gross examination of the specimen showed a firm yellow-tan, wellencapsulated mass with multicalcifications and fibrosis, measuring 14 × 12.5 3.5 cm and weighing 237 g. Microscopic examination showed lobulated deposits of amorphous eosinophilic material. Tissue section stained with Congo red showed congophilia with light microscopy and a typical green birefringence under polarized light. Some lobules were surrounded by multinucleated giant cells, a patchy lymphoplasmocytic infiltrate, multimicrocalcifications, and fibrosis. Loss of Congo red affinity after pretreatment with potassium permanganate suggested amyloid deposits composed of amyloid A fibrils. Hassall corpuscles were found near the amorphous eosinophilic material, which was confirmed by positive immunohistochemical stains for CK8/18. Additional observations indicated thickened arteriolar walls and narrowed arteriolar luminae. Immunohistochemical staining for CD138 confirmed infiltration of plasma cells. Further immunostaining indicated that these cells were positive for κ light chain and negative for the ≥ chain. Electrophoresis results revealed increasing levels of α1-globulin (6.58 g/L), α2-globulin (10.5 g/L), α-globulin (16.29 g/L), and κ (29.80 mg/L), as well as normal levels of ≥ (19.20 mg/L) and κ/≥ (1.55 mg/L). Results of other laboratory tests were normal except for mild anemia (118 g/L). To our knowledge, the presence of amyloidoma of the thymus constituted of amyloid A deposits associated with plasma cells of κ light-chain type has not been previously reported.

Acute Eosinophilic Pneumonia Associated With Inhaled Methamphetamines: A Previously Unreported Correlation

(Poster No. 42)

Kenneth C. Whithaus, MD (kwhithaus@usouthal.edu); Beth M. Rutland, MD. Department of Pathology, University of South Alabama, Mobile.

Acute eosinophilic pneumonia is a rare disorder that was first described in 1989. This disease can occur at any age but typically presents in patients 20 to 40 years of age and is more common in males than females. The presentation is an acute onset of marked respiratory insufficiency, often leading to the need for mechanical ventilation. Symptoms are generally nonspecific and include a high fever, tachypnea, and bilateral inspiratory crackles. A chest x-ray usually shows patchy parenchymal opacities. Bronchoalveolar lavage typically reveals 25% eosinophils; however, in some cases, no increase is noted. The histopathology of this disease consists of marked interstitial eosinophils with a lesser degree of alveolar eosinophils. Interstitial lymphocytes and organizing intra-alveolar fibrinous exudates are also a constant histologic finding. In addition, acute and organizing diffuse alveolar damage, type II pneumocyte hyperplasia, and perivascular intraluminal necrosis are commonly seen. The etiology of acute eosinophilic pneumonia has not been completely described but is currently thought to be an acute hypersensitivity reaction to an unidentified antigen. It is important to recognize this disease in contrast to other infectious forms of pneumonia, as treatment with steroids results in quick and dramatic recovery. We report a case of acute eosinophilic pneumonia in a 49-year-old man with a history of smoking crystal methamphetamines. Other reports and case series have identified cases that occurred following drug or chemical inhalation, most often with crack cocaine or heroin; however, a review of the literature revealed no previous reports linking acute eosinophilic pneumonia to inhaled methamphetamines.

Rosai-Dorfman Disease: A Rare Pulmonary Presentation

(Poster No. 43)

Patrick J. O'Donnell, DO (pjo113@hotmail.com); Jonathan K. Freeman, MD; Vandita Johari, MD. Department of Pathology, Tufts-Baystate Medical Center, Springfield, Mass.

Rosai-Dorfman disease (RDD), also known as sinus histiocytosis with massive lymphadenopathy, is a histiocytic proliferation of unknown etiology that most often involves cervical lymph nodes. Extranodal disease, usually limited to skin, bone, and the head and neck region, can occur in up to 40% of cases. Lower respiratory tract involvement is rare, mostly presenting near the subglottic superior trachea. An 82-year-old man presented with a 3-month history of hoarseness and hemoptysis. A computed tomography scan revealed a 5 × 4-cm masslike density in the superior segment of the left lower lobe with bilateral axillary and mediastinal lymphadenopathy. He underwent thoracoscopic wedge resection of the left lower lobe with axillary and mediastinal lymph node biopsies. Fresh tissue submitted for bacterial, fungal, and mycobacterial cultures revealed no growth. Histologic examination of the lung revealed a parenchymal lesion composed of histocytes with abundant pale eosinophilic cytoplasm and focal emperipolesis (Figure 48), which is characteristic of RDD. Extensive fibrosis, marked chronic inflammation, multinucleated giant cells, necrosis, and rare necrotizing granulomas were also present. Stains for acid-fast and fungal organisms were negative. Lymph node biopsies revealed morphologic findings typical of RDD. This case report highlights a rare pulmonary presentation of RDD, which raised the possibility of malignancy clinically and of infection morphologically. To our knowledge, this is the first reported case of RDD of the lung that is associated with necrotizing granulomatous inflammation, the significance of which is unknown.

Benign Hyperplastic Mesothelial Cells in Mediastinal Lymph Nodes: A Diagnostic Pitfall for Metastatic Carcinoma

(Poster No. 44)

Annisa L. Lewis, MD (ALLewis@tmhs.org); Jerad M. Gardner, MD; April Ewton, MD; Jae Y. Ro, MD, PhD. Department of Pathology, The Methodist Hospital, Houston, Tex.

Nonlymphoid tissue within lymph nodes usually indicates metastasis. Benign hyperplastic mesothelial cell inclusions within nodal sinusoids is a very rare occurrence, with a dozen cases reported in mediastinal nodes. The presence of cytokeratin-reactive, epithelioid cells within lymph nodes may be erroneously diagnosed as metastatic carcinoma. We report a case of benign hyperplastic mesothelial cells in a patient with a remote history of Hodgkin lymphoma that was treated with radiotherapy. A 44-year-old man presented with cardiac tamponade. Thoracic computed tomography scan showed pericardial and pleural effusions; pericardiocentesis showed serosanguinous fluid. During subsequent mediastinal thoracoscopy, pleura and pericardium were biopsied and histologically showed fibrinous pericarditis without evidence of malignancy. An enlarged mediastinal lymph node was found incidentally during the procedure and was excised;. histologically, clusters of large, bland, epithelioid cells with prominent nucleoli were seen distending the nodal sinusoids. Pleomorphism or mitoses were not identified. Immunohistochemistry was positive for cytokeratin, D2-40, and calretinin, and negative for carcinoembryonic antigen, Leu-M1, and TTF1; this confirmed the mesothelial origin of the cells. No malignancy was identified despite thorough clinical examination of the patient. Proper identification of the aberrant cells in lymph nodes is critical for appropriate patient management. Although rare, benign hyperplastic mesothelial cells should be included in the differential diagnosis for intranodal epithelioid cells. It is important to be aware of the possibility of benign mesothelial inclusions in the lymph node and to distinguish this entity from metastatic carcinoma, melanoma, Hodgkin lymphoma, or other malignancy to avoid unnecessary treatment and anxiety for the patient.

Benign Minor Salivary Gland Inclusion in a Pulmonary Hilar Lymph Node of a Patient With Invasive Well-Differentiated Adenocarcioma of the Lung

(Poster No. 45)

Annisa Lewis, MD (ALLewis@tmhs.org); Luan D. Truong, MD; Qui J. Zhai, MD. Department of Pathology, The Methodist Hospital, Houston, Tex.

Benign epithelial and nonepithelial inclusions have been found in lymph nodes in multiple body sites. These inclusions have been seen in cervical, axillary, mediastinal, abdominal, and pelvic lymph nodes. They appear as benign epithelial, parathyroid, decidual, mesothelial, angiolipomatous, or nevus cells or as Tamm-Horsfall protein. Although heterotopic salivary gland tissue is not infrequent in paraparotid lymph nodes, it has never been described in lymph nodes elsewhere, including those in pulmonary hilum. A 68-year-old woman with gastric lymphoma now in remission presented for routine follow-up and was found to have a lung mass. After a fine-needle aspiration biopsy diagnosis of adenocarcinoma, lobectomy and lymph node dissection were performed. Histologic sections of lung demonstrated a well-differentiated adenocarcinoma and a station nine lymph node (pulmonary ligament node) that was positive for metastatic adenocarcinoma. There was also another lymph node, which displayed a subcapsular nest of well-formed salivary glands occupying approximately one third of the nodal tissue. The inclusion was composed of acinar cells of both serous and mucinous types, but ductal type of cells was not seen. Identification of heterotopic tissue in lymph nodes is of great importance for patient management. Misdiagnosing benign glandular inclusions for metastasis could potentially lead to incorrect tumor staging. Benign minor salivary gland inclusions should be considered in the differential diagnosis when evaluating for metastatic adenocarcinoma. The salivary gland inclusion in pulmonary hilar lymph node may be histogenetically related to the minor salivary glands, which are located within the bronchial submucosa.

X-Linked Inhibitor of Apoptosis Protein Expression Is Associated With Decreased 5-Year Survival in Non-Small Cell Lung Cancer

(Poster No. 46)

Kirtee Rishi, MD1 (krishi@tmhs.org); Anna Sienko, MD1; Timothy Allen, MD2; Roberto Barrios, MD1; Abida Haque, MD1; Subhendhu Chakraborty, MS1; Quiqui (Jim) Zhai, MD1; Philip T. Cagle, MD.1 1Department of Pathology, The Methodist Hospital, Houston, Tex; 2Department of Pathology, University of Texas, Tyler.

Context: Resistance to apoptosis is a hallmark of many tumors and may be the underlying basis for suboptimal response to chemoradiation therapies. We determined the immunohistochemical expression of X-linked inhibitor of apoptosis protein (XIAP) in large series of lung cancers and evaluated the relationship between XIAP expression and 5-year patient survival.

Design: Tissue microarrays containing triplicate punch samples of 287 cases of non-small cell cancers, including 50 cases of carcinoids, 33 cases of small cell carcinoma, and 11 cases of large cell neuroendocrine cancer, were immunostained for XIAP (1:100 dilution, anti-hILP/XIAP; BD Biosciences, San Jose, Calif) using standard avidin-biotin techniques. Immunopositivity in tumor cells was graded on a scale from 0 to 3 and was averaged for the 3 punches from each tumor. Average score of 0 or 1 was classified as negative/weak expression, whereas average score of 2 or 3 was classified as strong positive expression. The relationship of XIAP expression to 5-year survival was studied using Kaplan-Meir curve and logrank test.

Results: XIAP expression (granular cytoplasmic staining) was observed in all cell types of lung cancer. Positive XIAP expression showed a statistically significant association with poorer 5-year survival in non-small cell lung cancer when all the lung cancer stages were considered (P = .39) between group 1 (negative/weak expression) and group 2 (strong positive expression).

Conclusions: XIAP is expressed in all cell types of lung cancer where it is potentially involved in resistance to traditional therapies. Positive XIAP expression is statistically associated with poor 5-year survival in non-small cell lung cancer.

Evolution of Histopathologic Findings in Postpartum Hemorrhage

(Poster No. 47)

Elizabeth G. Demicco, MD, PhD1 (egdemicco@partners.org); Drucilla J. Roberts, MD1; Jeffrey L. Ecker, MD2; Miriam D. Post, MD.1 Departments of 1Pathology and 2Obstetrics and Gynecology, Massachusetts General Hospital, Boston.

Context: Postpartum hemorrhage (PPH) is a major cause of maternal morbidity worldwide. Primary PPH occurs within 24 hours of delivery, whereas delayed PPH occurs 1 day to 6 weeks postpartum. Although often associated with placenta accreta or uterine rupture, the etiology of PPH frequently remains unknown and the timing of histopathologic changes in the uterus uncertain. This study aims to correlate histopathologic findings in PPH with the interval since delivery to ascertain potential causes of "idiopathic" PPH.

Design: Our institutional database was searched for cases of PPH during a 3-year period, excluding stillbirths and cases in which only the placenta was received or placenta accreta was histologically confirmed. Glass slides from available cases were examined for the presence of retained placenta, uterine vessel thrombi, maximum vessel diameter, and chronic endomyometritis.

Results: We identified 27 cases that met search criteria. Maternal age ranged from 24 to 46 years, and gestational age at delivery was 36 to 42 weeks. The postpartum interval since delivery ranged from minutes to 57 days, with 8 cases of immediate PPH (<24 hours), 13 cases of delayed PPH (2-21 days), and 4 cases of remote PPH ( 3 weeks). We reviewed the 25 available cases (6 gravid hysterectomies and 19 endometrial curetting) and scored them for histologic findings (Table).

Conclusions: We present new descriptions of histologic findings in PPH correlated to interval since delivery. These data suggest that delayed PPH is more strongly correlated with subinvolution, whereas remote PPH occurs more often in the setting of retained placenta and chronic endomyometritis.

POSTER SESSION 600: SATURDAY, SEPTEMBER 27, 2008, 1:30 PM-4:00 PM

Head, Neck, and Oral Pathology; Informatics; Neuropathology; Ophthalmic Pathology; Pathology Education; Practice Management; Quality Assurance; Transfusion Medicine and Coagulation

A Limited Immunohistochemical Panel Helps Differentiate Morphologically Similar Small Cell Malignancies of the Sinonasal Cavity and Nasopharynx

(Poster No. 1)

Jennifer R. Chapman-Fredricks, MD; Merce Jorda, MD, PhD; Carmen Gomez-Fernandez, MD (cgomez3@med.miami.edu). Department of Pathology, University of Miami/Jackson Memorial Hospital and The University of Miami Sylvester Comprehensive Cancer Center, Miami, Fla.

Context: Distinguishing small cell malignancies of the sinonasal tract and nasopharynx is difficult due to overlapping morphologic characteristics, particularly in small biopsies. However, distinguishing these entities is critical because of inherent differences in biology, natural history, prognosis, and treatment. We attempted to identify a limited immunohistochemical panel that may help differentiate these small cell malignancies.

Design: We reviewed 30 cases of histologically similar small cell malignancies of the sinonasal cavity and nasopharynx as follows: esthesioneuroblastoma (11); undifferentiated carcinoma (UC; 9), including 3 cases of tumors morphologically consistent with sinonasal undifferentiated carcinoma and 6 cases of nasopharyngeal undifferentiated carcinoma; basaloid squamous cell carcinoma (8); and small cell neuroendocrine carcinoma (2). Immunohistochemistry for pancytokeratin (CK), p63, synaptophysin, HLA-DR, and CK5/6 was performed using the labeled streptavidin-biotin method.

Results: All cases of basaloid squamous cell carcinoma, UC, and small cell neuroendocrine carcinoma were positive for CK and p63. Basaloid squamous cell carcinoma and UC were negative for synaptophysin, whereas cases of small cell neuroendocrine carcinoma were positive for synaptophysin. All cases of esthesioneuroblastoma were negative for both CK and p63, but were diffusely positive for synaptophysin. HLA-DR was positive in all cases of UC, whereas small cell neuroendocrine carcinoma, basaloid squamous cell carcinoma, and esthesioneuroblastoma were uniformly negative (Table). In the group of UC, immunohistochemistry for CK5/6 was in all cases positive in nasopharyngeal undifferentiated carcinoma and negative in sinonasal undifferentiated carcinoma.

Conclusions: A limited immunohistochemical panel of CK, p63, synaptophysin, and HLA-DR is useful in discriminating small cell malignancies of the sinonasal tract and nasopharynx. Further classification of UC into categories of sinonasal undifferentiated carcinoma or nasopharyngeal undifferentiated carcinoma may be facilitated by the use of CK5/6.

Large Cell Neuroendocrine Carcinoma of the Larynx: A Rare Neoplasm Distinct From Moderately Differentiated Neuroendocrine Carcinoma

(Poster No. 2)

David C. Spence, MD; James Lewis, MD (JLewis@path.wustl.edu). Department of Pathology and Immunology, Washington University, St Louis, Mo.

Context: Multiple series of atypical carcinoid (AC) have demonstrated a subset of patients with more aggressive tumors. A recent case report applied the World Health Organization classification of pulmonary neuroendocrine tumors to the larynx and diagnosed large cell neuroendocrine carcinoma (LCNEC). Based on this classification, a subset of the previously reported AC would be classified as LCNEC of the larynx. The 5- and 10-year survival rates for AC of the lung are currently 48% and 33%, respectively, whereas those for LCNEC are far worse. The historically inconsistent classification of laryngeal AC prevents a clear estimation of the number of cases of LCNEC and their prognosis.

Design: The archives at Washington University were searched for the term neuroendocrine and anatomic subsites. Cases of neuroendocrine carcinoma were evaluated with the World Health Organization criteria for pulmonary LCNEC. A literature search was performed for cases of laryngeal neuroendocrine carcinoma, and cases which could be clearly classified according to this scheme were included.

Results: Five cases meeting the World Health Organization criteria for LCNEC were identified (Table). Three were in house, and 2 were from the literature. There were 4 men and 1 woman. All were stage IVA at presentation. Eighty percent of the patients died of disease, and 75% of those patients died within 1 year of presentation.

Conclusions: LCNEC is a rare and distinct entity which appears to have a much worse prognosis than AC. Use of these well-defined criteria for classification will identify these patients for larger series to confirm this impression.

Ophthalmic Granulomatous Inflammation: Morphologic Findings and Clinical Correlation

(Poster No. 3)

John C. McCallum, BA1 (jmccallum@northwestern.edu); Julius W. Few, MD2; Debra L. Zynger, MD.1 Departments of 1Pathology and 2Plastic Surgery, Northwestern University, Chicago, Ill.

Context: Granulomatous inflammation is an occasional finding in ophthalmic pathology specimens. Diagnoses of nonspecific granulomatous inflammation or ruptured cyst are often given, but a more precise diagnosis is important for etiology-based therapy, which may consist of excision, antibiotics, topical or systemic steroids, or no treatment. In order to evaluate possible causes and facilitate directed therapy, this study defines the clinicopathologic characteristics of ocular granulomatous inflammation.

Design: We reviewed 292 surgical pathology reports of ophthalmic surgical pathology specimens accessioned from 2004 to 2007 and identified 30 cases with granulomatous inflammation. For these cases, patient charts and slides were reviewed.

Results: Thirty cases of granulomatous inflammation of the orbit, eyelid, and ocular adnexa were identified (20 women, 10 men; ages 26-80 years; mean age, 50). Special stains did not reveal infectious etiologies. One case of sarcoidosis was identified. Fifteen patients had prior procedures or trauma in the area, although this history was not given in most reports. In 4 cases diagnosed as nonspecific granulomatous inflammation or ruptured cysts, foreign material was retrospectively demonstrated, allowing for more accurate diagnoses. All 4 cases had unstated histories of blepharoplasty or orbital trauma.

Conclusions: Nonspecific ophthalmic granulomatous inflammation can often be more precisely diagnosed. We found that granulomatous inflammation in this region correlated to prior ocular procedures or trauma, often due to the presence of foreign material. Rare causes of granulomas, such as sarcoidosis, are seen and warrant further systemic investigation. Pathologists should be aware of these findings, as clinical history is often lacking and treatment varies by diagnosis.

Sporangia in Invasive Mucormycosis in a Patient With Promyelocytic Leukemia

(Poster No. 4)

Douglas W. Warden, MD (Douglas-Warden@ouhsc.edu); Kar-Ming Fung, MD. Department of Pathology, The University of Oklahoma Health Sciences Center, Oklahoma City.

Rhinocerebral mucormycosis is a potentially life-threatening complication in patients with hematologic malignancies. We present a rare case of mucormycosis identified histologically by the presence of sporangia. A 42-year-old woman with a history of acute promyelocytic leukemia presented with a maxillary sinus mass. A computerized tomography scan revealed destructive changes of the hard palate and maxilla, and surgical intervention was required. Intraoperative findings included bilateral diffuse necrosis of the nasal cavities, with significant destruction of the nasal septum, left nasal turbinate, and bony nasal floor. Specimens were sent for frozen section, permanent section, and fungal cultures. Frozen section of "left nasal contents" revealed fungal organisms with hyphae and nonviable collagenous tissue, suspicious for invasive fungal infection. On permanent section, the nasal contents were extensively necrotic (99% of submitted tissue) with fungal overgrowth, predominantly of angioinvasive growth pattern. Many hyphae were present that were irregular, ribbonlike, and pauciseptate with acute and right angle branching. Associated with the hyphae were sporangia and columella; these morphologic findings are characteristic of the class Zygomycetes, order Mucorales, which includes Rhizopus and Mucor. Fungal cultures grew Aspergillus flavus and Rhizopus sp. The patient has been receiving antifungal therapy and has required repeated sinonasal debridement. There has been no further extension of fungal infection. Diagnosis and management of fungal infection in immunocompromised patients often require a multidisciplinary approach. Histologic evaluation may provide early identification of mucormycosis and save valuable time in directing focused therapy (Figure 49).

Neuroendocrine Differentiation in Mucoepidermoid Carcinoma: An Immunohistochemical Study

(Poster No. 5)

Liza Escuadro, MD1 (lescuadro@gmail.com); Matthew L. Hearp, MD1; Elliot Weisenberg, MD.2 1Department of Pathology, University of Illinois at Chicago; 2Department of Pathology, Advocate Illinois Masonic Medical Center, Chicago.

Context: Mucoepidermoid carcinoma is a common malignant salivary gland tumor. Many immunohistochemical studies have documented its epithelial staining characteristics. Very few studies have examined expression of neuroendocrine markers. This study was prompted by a case of pulmonary mucoepidermoid carcinoma where carcinoid tumor was in the initial differential diagnosis and exhibited immunohistochemical expression of neuroendocrine markers, specifically neuron-specific enolase (NSE) and synaptophysin.

Design: Six cases of mucoepidermoid carcinoma identified from a search of the surgical pathology files of Advocate IllinoisMasonicMedical Center from January 2000 to June 2007 underwent immunohistochemical staining for NSE, synaptophysin, and chromogranin. The intensity of staining and the percentage of tumor cells staining were determined.

Results: The index case showed moderate staining intensity for NSE with minimal cells stained and strong staining intensity for synaptophysin with many cells staining. All of the nonindex cases stained with NSE and synaptophysin. The staining intensity for NSE varied from weak (1 case) to strong (1 case), with the 3 remaining nonindex cases showing moderate staining. The proportion of cells staining for NSE ranged from minimal (3 cases) to moderate (2 cases). The staining intensity for synaptophysin was weak for all of the nonindex cases. The proportion of cells staining for synaptophysin ranged from rare (1 case) to many (1 case), with the remaining 3 cases having a moderate number of cells staining positive. None of the cases exhibited staining for chromogranin.

Conclusions: Further evaluation is warranted; however, this study indicates mucoepidermoid carcinoma exhibits evidence of neuroendocrine differentiation by immunohistochemical methods.

Laryngeal Squamous Cell Carcinoma in a 13-Year-Old Adolescent and Association of Human Papillomavirus Types 16 and 18: A Case Report and Review of the Literature

(Poster No. 6)

Beth Joos,MD1 (hanan≥farghaly@yahoo.com); Nathan Joos,MD2; Jeffrey Bumpous, MD2; Carolyn Burns, MD1; Hanan Farghaly, MD.1 Departments of 1Pathology and 2Surgery, University of Louisville, Ky.

Squamous cell carcinoma (SCC) of the larynx is extremely rare in adolescents and children and has an aggressive nature and poor outcome. The mechanism of larynx oncogenesis is complex and controlled by various factors. Recently, it has been suggested that human papillomavirus (HPV)-positive laryngeal lesions have a better prognosis than HPV-negative lesions. There is very little knowledge of the role that HPV plays in these lesions. We report a case of a laryngeal SCC in a 13-year-old adolescent boy who presented with prolonged hoarseness. He reported no history of laryngeal intubation, radiation, alcohol use, or smoking. Laryngoscopic examination revealed a bulky lesion involving the right true vocal cord. Given these findings, the patient was scheduled for a biopsy of the lesion with a presumed diagnosis of laryngeal papilloma. Multiple biopsies were obtained from the right vocal cord for histologic diagnosis. The diagnosis of in situ and invasive SCC was established (Figure 50). The biopsy was assayed for infection with HPV types 6, 11, 16, 18, 31, 33, and 51 by in situ hybridization and staining with p16. There was diffuse and strong positivity staining for p16 in the tumor cells. In situ hybridization showed positivity for HPV DNA 16 and 18. Polymerase chain reaction was used to confirm the in situ hybridization HPV DNA results. In this case report of laryngeal SCC in a 13-year-old adolescent boy, we demonstrated coinfection by HPV types 16 and 18, which suggests HPV is a risk factor for developing laryngeal SCC in adolescents and children.

Nuclear Factor-<Bp65 Is Activated in Papillary Thyroid Carcinoma

(Poster No. 7)

Jing Liu, MD, PhD (Jing.Liu.1@uth.tmc.edu); Robert E. Brown, MD. Department of Pathology and Laboratory Medicine, University of Texas at Houston Medical School, Houston.

Context: Papillary thyroid carcinoma is the most common malignant neoplasm of the thyroid gland. Tumorigenesis of this neoplasm is not quite understood. The role of nuclear factor (NF)-κBp65 in the pathogenesis of papillary thyroid carcinoma has not been fully investigated. Expression of phosphorylated (p)-NF-κB by immunohistochemical staining has not been reported.

Design: We retrieved 20 cases of conventional-type papillary thyroid carcinoma from our files. Formalin-fixed, paraffin-embedded tissue sections were evaluated immunohistochemically for the expression of p-NF-κBp65 using a phosphospecific probe directed against Serine536, a putative site of activation (Cell Signaling Technology Inc, Danvers, Mass). We examined expression and localization of p-NF-κBp65 (Ser536). Both staining intensity (0-3+) and extensiveness (0%-100%) were evaluated for the expression of this marker. The positive staining intensity was graded as weak (1+), moderate (2+), and strong (3+).

Results: Expression of p-NF-κBp65 (Ser 536) was observed in all 20 cases with nuclear and cytoplasmic staining (1+ to 3+) in 20% to 100% of tumor cells, including moderate to strong nuclear staining intensity in 12 (60%) of 20 cases and moderate to strong cytoplasmic staining intensity in 17 (85%) of 20 cases.

Conclusions: The results indicate that there is constitutive activation of NF-κB in papillary thyroid carcinoma. The moderate to strong expression by immunohistochemical staining, especially the nuclear staining, suggests that NF-κB activation is involved in the tumorigenesis of papillary thyroid carcinoma and may represent a therapeutic target. The upstream pathways remain to be studied.

An Unusually Large Granular Cell Tumor at a New Location, the Pharynx: A Case Report and Literature Review

(Poster No. 8)

Xiaoxian Li, MD, PhD1 (xli@tmhs.org); Robert B. Parke, MD2; Anna Sienko, MD1; Qihui "Jim" Zhai, MD, PhD.1 Departments of 1Pathology and 2Surgery, The Methodist Hospital, Houston, Tex.

Granular cell tumor is a relatively uncommon benign neoplasm occurring in all ages. Incidence peaks in the third decade, and the tumor occurs more frequently in women (2:1) and African Americans (5:1). Granular cell tumor occurs often in the skin and subcutaneous tissue. Approximately half of the cases occur in the head and neck region, with one third of these occurring in the tongue. Less common sites include the lip, buccal mucosa, maxilla, palate, trachea, bronchi, gastrointestinal tract, breast, urogenital tract, neurohypophysis, and orbit. Granular cell tumor of the larynx is a well-recognized but uncommon lesion, accounting for approximately 3% to 10% of cases. Granular cell tumor of the pharynx, however, has not been reported. We report a case of granular cell tumor in the pharynx of a 53-year-old woman presenting with a retropharyngeal mass. Surgical excision revealed a 5.5-cm tan rubbery unencapsulated but circumscribed nodule. The tumor was composed of diffusely arranged oval and spindle cells with abundant eosinophilic granular cytoplasm and mildly pleomorphic nuclei. No necrosis or mitoses were seen. Immunostains showed the tumor cells were positive for S100 and vimentin and negative for smooth muscle actin, cytokeratin, desmin, and CD34. In addition to its unusual location, this tumor is extremely large, whereas most granular cell tumors are small (<2 cm). After extensive literature research, this case represents a unique example of a large granular cell tumor at a previously unreported location: the pharynx.

Hyalinizing Clear Cell Carcinoma of the Salivary Gland: Clinicopathologic Characteristics and Diagnostic Challenges

(Poster No. 9)

Emerald D. O'Sullivan-Mejia, MD1 (eo'sullivan-mejia@mcvh-vcu.edu); William C. Faquin, MD, PhD2; Celeste N. Powers, MD, PhD.1 1Department of Pathology, Virginia Commonwealth University Health Systems, Richmond; 2Department of Pathology, Massachusetts General Hospital, Boston.

Hyalinizing clear cell carcinoma (HCCC) of the salivary gland is a rare neoplasm with a female predominance. Treatment for this indolent tumor includes wide surgical excision with/without adjuvant radiotherapy. It is important to differentiate HCCC from other more aggressive clear cell tumors, such as the following: mucoepidermoid carcinoma, epithelial myoepithelial carcinoma, acinic cell carcinoma, odontogenic neoplasms, and metastatic renal cell carcinoma. We report a case of HCCC to highlight the important clinicopathologic features and the diagnostic challenges of this rare entity. A 59-year-old woman presented with progressive dysphagia and a 4 2-cm mass at the base of the left tongue. Histologically, the tumor consisted of cords, trabeculae, and nests of monomorphic clear epithelial cells, as well as cells with eosinophilic granular cytoplasm, traversing a hyalinized stroma (Figure 51). There was minimal atypia and rare mitoses. The tumor cells were periodic acid-Schiff, p63, cytokeratin AE1/AE3, polyclonal carcinoembryonic antigen, and epithelialmembrane antigen positive with a low proliferation index (Ki-67). The tumor cells were negative for S100, desmin, actin, and mucin. Although the histologic characteristics of HCCC have been reported in rare case reports and small series, the diagnosis of this carcinoma is still challenging. Immunohistochemical stains may help differentiate HCCC from other tumors composed of clear cells. Clear cell mucoepidermoid carcinoma is mucin positive; epithelial myoepithelial carcinoma is smooth muscle actin and S100 positive; acinic cell carcinoma is periodic acid-Schiff positive and diastase resistant; odontogenic tumors are S100 positive; and renal cell carcinoma is renal cell marker, CD10, and cytokeratin positive.

Human Papillomavirus in Head and Neck Squamous Cell Carcinomas: An Equal Opportunity Infection in Both Males and Females

(Poster No. 10)

P. C. Desai, MD1 (hanan≥farghaly@yahoo.com); M. V. Jaglal, MD1; G. Schaefer, BSc3; P. Gopal, MD2; S. J. Ghim, PhD3; D. M. Miller, MD, PhD3; H. Farghaly, MD2; A. B. Jenson, MD.1 Departments of 1Internal Medicine and 2Pathology and 3The James Graham Brown Cancer Center, University of Louisville, Louisville, Ky.

Context: Human papillomavirus (HPV) is found in up to 25% to 30% of head and neck squamous cell cancers and has been shown to yield a better prognosis. Currently, there is no routine testing in these samples for HPV.

Design: Records (2000-2007) were searched for cases diagnosed as neck lymph nodes with metastatic squamous cell carcinoma. The search yielded 41 patients. Samples were examined using polymerase chain reaction (PCR) sequencing and staining for p16.

Results: Forty-one patients (34 male, 7 female) were evaluated. The HPV incident rate was 29% by PCR, and 10% of samples were positive by diffuse and strong p16. Seven samples were positive by PCR and diffusely and strongly positive by p16. Four additional samples that were PCR positive were either focally positive or positive but not as strongly for p16. One sample that was PCR positive was p16 negative. Four additional samples were positive by p16 only. HPV subtypes were determined by sequencing the positive PCR product, yielding HPV 16 (10/12), HPV 33 (1/12), and HPV 45 (1/12). Thirty-nine of 41 patients had at least occasional documented alcohol use. The 2 that denied alcohol use were both HPV positive. Twenty-eight percent of females and 26% of males were HPV positive.

Conclusions: Twenty-nine percent of PCR samples and 45% of samples overall were positive for HPV, an alarming rate. More important, there was no significant predilection for sex or age in this study. Since HPV has been documented to be a positive prognostic indicator, HPV staining is recommended on all head and neck squamous cell cancers.

Expression of G-Protein Receptor 30 in Squamous Cell Carcinomas of the Head and Neck by Immunohistochemistry

(Poster No. 11)

David M. Rogers, MD1 (drogers@salud.unm.edu); Nicole Bryan, MD2; Hugo Arias-Pulido, PhD3; Eric R. Prossnitz, PhD1; Therese J. Bocklage, MD.1 Departments of 1Pathology, 2Ear, Nose, and Throat Surgery, and 3Obstetrics and Gynecology, University of NewMexico School ofMedicine, Albuquerque.

Context: G-protein receptor 30 (GPR30) is an estrogen-binding G-protein receptor that activates epidermal growth factor receptor. GPR30 overexpression in ovarian cancers is associated with more aggressive disease. Epidermal growth factor receptor is a prognostic indicator and therapeutic target in head and neck squamous cell carcinoma (HNSCC), but potential action of GPR30, a mediator of epidermal growth factor receptor activation and therefore possible promoter of HNSCC tumor proliferation, has not been examined.

Design: Fifty-one cases of HNSCC from the tonsil, oropharynx, larynx, and tongue were drawn from the files of the University of New Mexico Hospital from 2001 through 2005 (35 men and 16 women; overall average age of 55 years). Paraffin tissue blocks of representative tumor were cored and assembled into microarrays. Immunohistochemical staining was performed on the microarrays using standard techniques with antibody specific to GPR30. Two pathologists independently graded the cores using a 4-point scale. Clinical data, including stage, were collected with an average of 3.6 years of follow-up.

Results: There was excellent interobserver agreement in grading. Strong positive staining was present in 19 cases (37%). Tumor grade did not correlate with GPR30 expression. Tumor location, primary size, and stage did not correlate with GPR30 expression.

Conclusions: This study is the first to examine expression of GPR30 protein in HNSCC. Although known as an activating protein in estrogenmediated cell proliferation, its expression in more than one third of HNSCC cases may indicate a novel significant route to activation of epidermal growth factor receptor in these tumors.

Funding/Support: This work was supported in part by grant CA127731 from the National Institutes of Health (Dr Prossnitz) and by grants from the Strahen Foundation and the Foucar Fund.

The Healthcare Continuum: Connecting Research and Patient Care Information

(Poster No. 12)

Charles Jaffe, MD, PhD (cjaffe@hl7.org). Office of the CEO, Health Level 7, Del Mar, Calif.

Context: Information from clinical research remains siloed from the context of patient care. Research findings currently require more than 15 years before they become integrated into clinical practice. One of the critical barriers to this process has been the inability to share data derived from clinical research with the health care community. At the same time, patient care data have not effectively informed bench research. Health Level 7 has been the global standard for data interoperability in patient care, but has also embraced the domain of clinical research in an effort to lower this barrier.

Design: Health Level 7 has had a global presence in patient care for more than 2 decades. Health Level 7 has provided interoperability requirements for patient care, including administrative content, electronic health records, laboratory data, and images. The Reference Information Model serves as the framework for model-driven standards development embodied in version 3. In collaboration with the Clinical Data Interchange Standards Consortium, the international standards organization for regulated clinical research, the clinical research domain has been mapped into the Reference Information Model.

Results: The Biomedical Research Integrated Domain Group has evolved this model with additional support from the National Cancer Institute, the Food and Drug Administration, and Health Level 7. It integrates into the Reference Information Model both business and functional requirements for research, and supports a wide range of vocabulary and data standards without compromising flexibility for new technologies (genomics) and evolving clinical requirements (decision support).

Conclusions: The Biomedical Research Integrated Domain Groupmodel seamlessly enables the interoperable exchange of patient and research information within the framework of existing standards.

The Important Technical Aspects in Whole Slide Imaging for Multiple Purposes

(Poster No. 13)

Yukako Yagi, PhD (yyagi@partners.org); John R. Gilbertson, MD. Department of Pathology, Harvard Medical School, Boston, Mass.

Context: Whole slide imaging (WSI) has made impressive progress during the past 10 years, not only in technology (faster scanning and better image quality), but also in the number of applications in pathology, such as image analysis and enhancement. Furthermore, developers are also looking at WSI as a front end for computer-aided diagnosis tools and for anatomic pathology laboratory information systems in conjunction with other relatively new technologies. In this circumstance, the quality and accuracy of image data (how accurate), relationship between other devices, and relationship between each aspect are becoming increasingly important.

Design: This study examined the importance of optical optimization in WSI and the effect of slide quality (tissue section thickness and consistency), parameters outside the direct control of the imaging devices themselves, on WSI capture speed and image quality.

Results: Preliminary data indicate that thinner, more consistent tissue sectioning, such as those produced by automated tissue sectioning robots, results in significantly faster WSI capture times and better image quality. The results indicate that the appropriate use of optical filters and thinner and more consistent tissue sectioning (such as those produced by automated tissue sectioning robots) could measurably improve the appearance and resolution of WSI.

Conclusions: There are many aspects that influence the quality of WSI. Also, there are many aspects we have to consider for clinical implementation. We will keep conducting a series of experiments to improve WSI and to use WSI most effectively.

Improved Workflow Through an Online Relational Call Log for Clinical Pathology

(Poster No. 14)

Eric Duncavage, MD1 (eduncavage@path.wustl.edu); Benjamin Ryan, BS1; Mitchell Scott, PhD2; Charles Eby, MD.2 Departments of 1Anatomic and Molecular Pathology and 2Laboratory and Genomic Medicine, Washington University, St Louis, Mo.

Context: Laboratory medicine residents evaluate the appropriateness for many laboratory test requests. Providing effective consultations requires specific knowledge about the underlying disease process, laboratory logistics, and test methodology. A method to reliably follow up on test results with long turnaround times is essential for resident education.

Design: A relational database was written using standard query language to track requests for tests requiring approval, provide follow-up for results, and facilitate resident education. This database was shared online using the PHP scripting language. To protect patient information, the database was password protected and hosted behind a firewall. Pertinent information was entered via the Web by the on-call resident. To facilitate education, deidentified records were made searchable by other residents and faculty. Additionally, a "presentation mode" was created that allows calls to be easily presented.

Results: The call log consists of 21 fields, including requesting physician, patient history, call question, and resolution. A flag for calls requiring follow-up was also included to facilitate the addition of test results. In the first months of use, an average of 70 calls per month was logged. The majority of these calls pertained to consultations for clinical chemistry and molecular genetic tests.

Conclusions: A Web-enabled database was developed that provides a method for tracking laboratory tests requiring resident consultation, facilitates hand-off of cases, and serves as a searchable resource. The addition of a presentation mode further streamlines call discussion. The logged calls have also served to set a precedent for similar situations, resulting in improved consistency and better-defined approval criteria.

Petri Net Modeling of a Surgical Pathology Operation

(Poster No. 15)

Frank Schneider, MD (frank.schneider@duke.edu). Department of Pathology, Duke University Medical Center, Durham, NC.

Context: Petri Nets (PNs) are graph-based tools that show the flow of abstract objects through complex systems. They have been used successfully for safety and reliability modeling in various industries.

Design: A PN representing a simplified surgical pathology operation is designed. The flow of specimens through different locations of the operation is represented. Specimen flow transitions are delayed by specimen processing, such as grossing or interpretive efforts by a pathologist. The delay of flow is modeled by individual transition parameters for each location.

Results: A PN can describe and visualize the structure of a surgical pathology operation to any desired degree of complexity. The PN allows assessment of specimen flow through the system. The model can identify and localize delays in the specimen flow that might affect the outcome of the surgical pathology operation.

Conclusions: PN modeling offers a systematic tool to describe a surgical pathology operation and its dynamic behavior. It is useful for visualizing the workflow through the system. Identification of timeliness or reliability problems in surgical pathology using PNs may be a useful adjunct to the series of quality assurance monitors employed by most laboratories. Implementation and use of PNs can be facilitated by software tools.

Real-Time Telepathology for Intraoperative Neuropathology Consultation

(Poster No. 16)

Nikolaj P. Lagwinski, MD (lagwinn@ccf.org); Richard Prayson, MD. Department of Pathology and Laboratory Medicine, Cleveland Clinic, Cleveland, Ohio.

Context: Dynamic telepathology has been studied extensively for routine practice, but few studies have reported on its use for subspecialty intraoperative consultation. We present an evaluation of a real-time, robotic telepathology system specifically focusing on neuropathology frozen sections.

Design: Forty-eight cases were analyzed retrospectively using the Trestle Corporation (Newport Beach, Calif) MedMicro system. The neuropathologist (R.P.) had no knowledge of prior frozen section or final diagnoses and was given only the age and sex of the patient as well as any pertinent clinical information that was available on the surgical pathology requisition form at the time of the original intraoperative consult. Slides were then randomized and later reviewed by light microscopy by the same neuropathologist to assess concordance between telepathology and light microscopy diagnoses. Discrepancies were subclassified as diagnostic discordances or grading discordances. The time needed for each consultation was also recorded.

Results: Forty-three (89.6%) of 48 cases showed concordance. Of the remaining cases, 2 (4.2%) of 48 showed diagnostic discordance, whereas 3 (6.2%) of 48 showed grading discordance. The mean time of a telepathology consultation was 5 minutes (range, 1-16 minutes), with 37 cases (77.1%) requiring 3 minutes. Light microscopy consultation times ranged from 1 to 5 minutes, with 37 cases (77.1%) requiring 1 minute or less.

Conclusions: We observed high rates of concordance between telepathology and light microscopy diagnoses. Real-time telepathology is a feasible option for intraoperative neuropathology consultations, although the time required is greater than for traditional light microscopy.

Familial Creutzfeldt-Jakob Disease Associated With the E200K-129V Mutation and Type 2 Prion Protein Expression: A Rare Haplotype

(Poster No. 17)

Saud S. Rahman, MD (saudsrahman@yahoo.com); Mary Jo N. Martin, MD; Nitya Ghatak, MD. Department of Pathology, Virginia Commonwealth University Health System, Richmond.

Familial Creutzfeldt-Jakob disease (fCJD) is an inheritable type of prion disease that accounts for 15% of all reported cases of CJD. Unlike themore common sporadic form of CJD (sCJD), fCJD is associated with pathogenic mutations in the human PrP gene (PRNP). The most common PRNP haplotypes identified in fCJD are E200K-129M and D178N-129V, both of which are associated with the type 1 prion protein (PrPSc). We present a case of fCJD associated with the E200K-129V mutation and expression of type 2 PrPSc, an exceedingly rare haplotype first described in 1999 in an elderly woman with dementia. Our patient was a 66-year-old white woman who presented for management of ataxia, gait disturbance, and memory decline. Electroencephalographic studies revealed abnormal dysrhythmic activity, and cerebrospinal fluid analysis was positive for the 14-3-3 protein. The patient died 2 months after onset of symptoms. Autopsy findings revealed spongiform changes in the neuropil and neuronal cytoplasm in the cerebrum and cerebellum (Figure 52).Western blot analysis of frozen autopsy brain tissue demonstrated the presence of type 2 PrPSc. Genetic sequencing analysis detected the E200K mutation in the PRNP coupled with the valine codon at position 129, establishing a diagnosis of fCJD. In comparison to individuals with other fCJD haplotypes, those affected with the E200K-129V mutation demonstrate dissimilar clinical features and histologic findings, which include abnormal accumulation of type 2 PrPSc plaques, primarily within the cerebellum. Our case is notable for its rapid clinical course, and it highlights the diagnostic importance of genetic analysis in suspected CJD cases.

Hereditary Hemorrhagic Telangiectasia Is a Rare Cause of Seizures in Children

(Poster No. 18)

Jennifer G. Pryor, MD1 (Jennifer≥Pryor@urmc.rochester.edu); Caroline R. Dignan, MD2; James M. Powers, MD.1 1Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY; 2Monroe County, Office of the Medical Examiner, Rochester, NY.

Hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu syndrome) is a systemic vascular dysplasia with an autosomal dominant mode of inheritance. Features include visceral arteriovenous malformations in the pulmonary, hepatic, and cerebral vasculature and mucocutaneous telangiectases that frequently lead to epistaxis or gastrointestinal bleeding. Although recurrent epistaxis is a classic presentation of the disease in adults, presentation in children may be atypical, since the disease is still developing. We present a 13-year-old adolescent girl with a family history of Osler-Weber-Rendu syndrome and recent, sudden onset of severe headaches and seizurelike activity. Radiographic studies, including magnetic resonance imaging and computed tomography, were negative. Five days after initial presentation, the patient developed severe epistaxis with loss of consciousness; she then became asystolic and could not be rescuscitated. Complete postmortem examination revealed capillary telangiectases involving the right frontal cortex and right superior cerebellar hemisphere without evidence of recent hemorrhage. Abnormal vessels in the right frontal cortex had thickened walls and endothelial proliferation with gliotic intervening brain, neuronal loss, and chronic astrogliosis. There was no evidence of pulmonary or hepatic vascular malformation. Toxicology screen was negative. Cause of death was listed as hereditary hemorrhagic telangiectasia with probable terminal convulsive disorder with capillary telangiectases of the brain. Manner of death was natural. In conclusion, hereditary hemorrhagic telangiectasia is an uncommon cause of seizures in children and may lead to terminal convulsive disorder.Hereditary hemorrhagic telangiectasia should be strongly suspected in a symptomatic child with a positive family history, even when clinical presentation is atypical and initial work-up is negative.

Atypical Multiple Sclerosis Variant Associated With Cerebral Amyloid Angiopathy

(Poster No. 19)

Aditya Raghunathan,MD1 (araghun1@hfhs.org); Rajan Jain,MD2; Norman L. Lehman, MD, PhD.1 Departments of 1Pathology & Laboratory Medicine and 2Radiology, Henry Ford Hospital, Detroit, Mich.

In cerebral amyloid angiopathy, amyloid deposition occurs in themedia and adventitia of small- to medium-sized meningeal and cerebral blood vessels. We present an unusual case of a patient with clinical symptoms of multiple sclerosis but with a biopsy demonstrating cerebral amyloid angiopathy. A 40-year-old woman presented with progressive right facial anesthesia and paralysis. She later developed right limb weakness and seizures. Magnetic resonance imaging of the brain demonstratedmultiple white matter lesions that were predominantly periventricular. The majority showed open/incomplete ring enhancement. A few subcortical lesions appeared somewhat more confluent. The radiologic differential diagnosis included multiple sclerosis, Lyme disease, intravascular lymphoma, and vasculitis, but not cerebral amyloid angiopathy. The latter usually presents as confluent white matter lesions with edema and mass effect or as acute hemorrhage. Her cerebrospinal fluid, however, lacked oligoclonal bands. Because of these discordant findings, a stereotactic cerebral biopsy was performed. The biopsy showed mild perivascular lymphocytic infiltrates, predominantly CD3 immunopositive, within the cortex and white matter. Several small blood vessels were thickened and appeared hyalinized. Amorphous amyloid-like deposits were present in the cortex, which showed apple-green birefringence with Congo red. A β-amyloid immunohistochemical stain was positive in the vessel walls and the parenchymal deposits. Subsequently, the patient's symptoms worsened and her cerebrospinal fluid then showed oligoclonal bands. The clinical history and histopathologic findings in this case are consistent with an uncommon variant of multiple sclerosis that is associated with cerebral amyloid angiopathy and perivascular lymphocytic infiltrates. It is important to consider this variant of multiple sclerosis in cases with atypical clinical, radiographic, and biopsy findings.

Acute Balamuthia mandrillaris Encephalitis: A Case Report From Hawaii

(Poster No. 20)

Stella Marie M. Wenceslao, MD1 (swencesl@hawaii.edu); Steven T. Komura, MD2,3; Jane H. Uyehara-Lock, MD.2 1Department of Pathology, University of Hawaii Residency Program, Honolulu; 2Department of Pathology, University of Hawaii, John A. Burns School of Medicine, Honolulu; and 3Hawaii Medical Center, Honolulu.

Balamuthia mandrillaris, a free-living soil amoeba, has emerged as a causative agent of chronic granulomatous amoebic encephalitis in both immunocompromised and immunocompetent hosts. Balamuthia infections follow a clinical course similar to that of Acanthamoeba spp, with chronic neurologic complaints with or without history of cutaneous lesions and with onset from 2 weeks to 2 years. Because of the nonspecific neurologic signs and symptoms, amebic encephalitis is rarely diagnosed prior to death. We report the first case in Hawaii of B mandrillaris encephalitis in a 42-year-old man. This patient had a history of hepatitis C and intravenous drug use with deteriorating mental status and lethargy for 10 days following a fall. Imaging studies of the brain revealed abnormalities compatible with laminar necrosis, hemorrhage, and calcifications. Brain biopsies revealed acute encephalitis with organisms consistent with amoebae. Analysis with polymerase chain reaction done at the Centers for Disease Control and Prevention identified the amoeba as B mandrillaris. The patient died 6 days after the biopsy. Because the histologic appearance of Balamuthia is morphologically indistinguishable from Acanthamoeba spp, it is essential to distinguish between these entities, as treatment protocols are different.

A Clinically and Histologically Aggressive Desmoplastic Infantile Ganglioglioma in an 8-Month-Old Boy

(Poster No. 21)

Douglas Larsen, MD (dalarsen@swmail.sw.org); Vickie Willoughby, DO; V. O. Speights, DO. Department of Pathology, Scott & White Hospital and Texas A&M Health Science Center, Temple.

Desmoplastic infantile ganglioglioma (DIG) is a rare intracranial tumor of early childhood with a generally good prognosis following surgical resection, corresponding to World Health Organization grade I. We present a case of DIG with anaplastic features and aggressive clinical course. An 8-month-old infant boy without significant medical history was admitted for poor feeding tolerance and multiple episodes of vomiting during 5 to 6 days. A computerized tomography scan of the head revealed an enhancing hemorrhagic 7.2 × 6.3-cm left temporoparietal mass. The patient underwent immediate neurosurgical intervention, and a left anterior temporal lobectomy was performed. Histologic studies demonstrated a heterogenous neoplasm consisting of a small cell component that resembled a primitive neuroectodermal tumor with an additional astrocytic component containing gemistocytic astrocytes and ganglioid cells in a desmoplastic stroma. Immunohistochemically, the astrocytic areas were positive for glial fibrillary acidic protein, synaptophysin, CD99, and S100. The small cell component showed negative staining for muscle, epithelial, pan-leukocyte, glial, and neuronal markers with variable FLi-1 positivity. MIB-1 labeling index was low in the astrocytic element and moderate to high in the small cell component. Magnetic resonance imaging of the brain performed at 3 and 6 months after surgery demonstrated tumor recurrence and leptomeningeal spread. Few reports of DIG with histologic anaplasia and metastases are present in the literature, some with poor clinical outcomes. These rare cases, including our own, indicate a wider spectrum among DIGs than previously considered. These anaplastic features are important to identify and may signal the necessity for additional treatment.

Cytologic Diagnosis of Paraesophageal Ganglioneuroma

(Poster No. 22)

Summer L. Nugent, MD (summerlindsay@gmail.com); Daniel C. Dim, MD; Hong Q. Peng, MD. Department of Pathology, University of Maryland, Baltimore.

Endoscopic ultrasound-guided fine-needle aspiration is a well-established modality in the detection and diagnosis of mediastinal lesions. Ganglioneuroma is a benign, rare, soft tissue neoplasm arising from sympathetic ganglion cells, and complete surgical resection is considered to be curative. Ganglioneuroma in a surgical specimen is a straightforward diagnosis; however, due to the rarity of this entity, diagnosis by fineneedle aspiration is more challenging. We describe a case of a paraesophageal ganglioneuroma diagnosed by endoscopic ultrasound-guided fineneedle aspiration. A 75-year-old man with a history of non-small cell lung cancer was noted to have a mediastinal mass on chest computed tomography. Upper endosonography identified a 40 17-mm mass extrinsic to the thoracic esophagus. An endoscopic ultrasound-guided fine-needle aspiration of the mass was performed. Smears of the aspirate revealed rare fragments of bland spindle cells intermingled with ganglion cells. Immunohistochemistry was performed on a cell block preparation using an autostainer (Benchmark XT, Ventana Medical Systems Inc, Tucson, Ariz). Both the spindle and ganglion cell components were positive for S100 protein (Ventana Medical Systems Inc) and negative for pancytokeratin, CD117, and actin (Cell Marque Corp, Hotsprings, Ariz). The cytomorphology and immunohistochemical profile were consistent with ganglioneuroma. We discuss the diagnostic pitfalls and differential diagnoses of ganglioneuroma, emphasizing the importance of thorough clinical history, attention to cytologic detail, and corroborating immunohistochemistry in arriving at the correct diagnosis. Our case represents one of the few reported cases of ganglioneuroma diagnosed by endoscopic ultrasoundguided fine-needle aspiration cytology.

Anaplastic Meningioma with Osteosarcomatous and Lipomatous Differentiation

(Poster No. 23)

Krista L. Pekarski, MD (pekarsk@ccf.org); Richard Prayson, MD. Department of Pathology and Laboratory Medicine, Cleveland Clinic Foundation, Cleveland, Ohio.

Meningiomas account for 13% to 26% of primary intracranial tumors with anaplastic or malignant (World Health Organization grade III/III) meningiomas constituting only 1% to 2.8% of meningiomas. Anaplastic meningiomas exhibit a high mitotic index and malignant cytology. Metaplastic elements have been documented, including osseous, cartilaginous, and lipomatous changes. Anaplastic meningioma with osteosarcomatous differentiation is distinctly uncommon in the absence of prior radiation. We report a case of a 63-year-old man without a radiation history who presented with an anaplastic meningioma with osteosarcomatous and lipomatous components. The patient presented with a 6-week history of left-sided weakness, dizziness, headaches, and incoordination.Neurologic examination demonstrated multiple deficits, including abnormal gait, decreased sensation of the extremities, limited visual field, nonreactive pupil, facial droop, and absent gag reflex. Magnetic resonance imaging revealed a 5.8-cm, right parietal enhancing lesion containing central necrosis with mass effect and midline shift consistent with a high-grade glioma or lymphoma. He underwent surgical resection. Calcification and necrosis were identified grossly. Histologic examination revealed a predominantly spindled cell, anaplastic meningioma marked by perivascular whirling, hypercellularity, psammoma bodies, up to 29 mitoses per 10 high-power fields, focal palisading necrosis, and brain invasion. Prominent nucleoli and small cell change were not appreciated. Malignant bone formation and benign adipose tissue were also present. The tumor was not immunoreactive with antibodies to glial fibrillary acidic protein and epithelial membrane antigen. The Ki-67 labeling index was 37%. Metaplasia is a well-documented finding in a rare meningioma. Osteosarcomatous differentiation in the absence of prior radiation has not been reported in anaplastic meningiomas.

Sclerosing Paraganglioma of the Filum Terminale

(Poster No. 24)

Marie Rivera-Zengotita, MD1 (riveraze@bcm.edu); Jianyi Li, MD, PhD2; Hidehiro Takei, MD, PhD2; Gregory N. Fuller, MD, PhD3; Suzanne Z. Powell, MD.2 1Department of Pathology, Baylor College of Medicine, Houston, Tex; 2Department of Pathology, The Methodist Hospital, Houston, Tex; 3Department of Pathology, M. D. Anderson Cancer Center, Houston, Tex.

A distinctive variant of paraganglioma, sclerosing paraganglioma, has been previously described in the carotid body region, parapharyngeal region, and mediastinum. We report a single case of sclerosing paraganglioma of the filum terminale. The resection specimen consisted of an encapsulated/well-circumscribed oval nodule. Histologically, the tumor was composed of large round to polygonal cells with moderate nuclear pleomorphism, prominent nucleoli, and abundant granular eosinophilic cytoplasm arranged in nests and cords separated by extensive stromal collagenization or hyalinized fibrous tissue. In some areas, the tumor cells were spindle with elongated nuclei and scant cytoplasm and formed irregular islands surrounded by hyalinized fibrous bands. Binucleated and multinucleated tumor cells were occasionally seen. Both central and peripheral sclerosis was present, with the latter one giving the tumor a pseudoinfiltrative growth pattern. Mitotic activity was inconspicuous.Necrosis was not identified. Immunohistochemical stains showed strong diffuse positivity for chromogranin, synaptophysin, and neuron-specific enolase in the paragangliomatous component. Scattered sustentacular cells surrounding the tumor nests were positive for S100 protein. Cytokeratin expression was also observed. Simple local excision was curative. Sclerosing paraganglioma may represent a diagnostic challenge due to its histologic resemblance to invasive carcinoma or a malignant spindle cell lesion. Careful inspection to search for areas of classic paraganglioma along with the appropriate immunohistochemical stains should help in distinguishing this lesion. To our knowledge, this is the first report of a sclerosing paraganglioma of the filum terminale.

Morphologic Spectrum of Progression in High-Grade Meningioma: A Report of 2 Uncommon Cases

(Poster No. 25)

Roni J. Bollag, MD, PhD1 (rbollag@mcg.edu); John R. Vender, MD2; Suash Sharma, MD.1 Departments of 1Pathology and 2Neurosurgery,Medical College of Georgia, Augusta.

A recent trend in the literature evokes 2 pathways for malignant progression in meningiomas: de novo anaplastic meningioma (ostensibly with better prognosis) and transformed meningioma from lower grade (presumed worse prognosis). This pattern is akin to that for gliomas but with dissimilar prognostic connotations.We present 2 cases of transformedmeningiomas that display a spectrum of tumor morphologies (Table). Case 1 at presentation showed a random admixture of grade I meningothelial, atypical, and anaplastic meningioma morphologies. The tumor recurred as anaplastic meningioma. Case 2 presented initially as an atypical chordoid meningioma. However, the tumor recurred as an anaplastic meningioma predominantly at the invasive front, with portions showing a papillary configuration (typically seen in childhood meningiomas). Foci of residual chordoid pattern could also be discerned. These 2 cases illustrate morphologic progression from grade II to anaplasia, including a novel occurrence of grade III transformed from chordoid meningioma. In view of the recent suggestion of prognostic differences between de novo and transformed high-grade meningiomas, genetic characterization akin to that used for gliomas may be warranted to establish genotypic evolution and to help stratify prognostic subcategories for higher-grade meningiomas.

Neuropathology of Ornithine Transcarbamylase Deficiency

(Poster No. 26)

Yvonne S. Noronha, MD (lynoronha@gmail.com); Craig Zuppan, MD; Ravi Raghavan, MBBS, MD, MRCPath. Department of Pathology, Loma Linda University Medical Center, Loma Linda, Calif.

Ornithine transcarbamylase (OTC) deficiency is a rare urea cycle disorder typically presenting at birth. This X-linked syndrome results from a genetic deficiency of mitochondrial OTC, which catalyzes the conversion of ornithine and carbamoyl phosphate to citrulline. Detailed neuropathologic descriptions of this condition are scarce. We report on a 3-year-old boy with known OTC deficiency, mental retardation, and developmental delay, who died of complications following surgery for cecal perforation. At autopsy, the brain demonstrated massive bilateral hydrocephalus, with white matter atrophy, and extensive resolving infarcts of the frontal and occipital lobes and basal ganglia. This was associated with marked reactive astrocytosis, including prominent gemistocytes in a focally pallisading pattern, to an extent that it invited confusion with glioma. Mineralization of glial cells was noted in the basal ganglia and thalamus. The cerebellum showed ischemic neurons in the dentate nucleus, along with "grumose change," a recently described feature of this condition. Our patient did not show cavitating multicystic encephalopathy or demyelinating lesions, which have been described in other cases. The pathogenesis of the multifocal cerebral infarcts is uncertain in our case, as the severity of the lesions could not be explained by multiorgan failure alone. However, studies in experimental mice with congenital OTC deficiency implicate an energy deficit caused by an adverse effect on pyruvate oxidation and brain adenosine triphosphate production as a cause of neuronal death. Alternatively, excitotoxic cell death secondary to toxic metabolites generated in OTC deficiency may also play a role.

Sacrococcygeal Medulloepithelioma: Report of a Rare Case

(Poster No. 27)

Yvonne S. Noronha, MD1 (lynoronha@gmail.com); Ravi Raghavan, MBBS, MD, MRCPath1; Fae Majlessipour, MD2; Craig Zuppan, MD.1 Departments of 1Pathology and 2Pediatrics, Loma Linda University Medical Center, Loma Linda, Calif.

Medulloepithelioma is a rare, highly aggressive neoplasm typically occurring in the brain or eye of children that only rarely presents at other extraneural sites. We report on a 3-year-old girl with multiple congenital malformations, including Dandy-Walker variant with seizure disorder, who presented with an 8-cm predominantly cystic tumor adjacent to the coccyx. Microscopically, it showed features of malignancy, with distinct pseudostratified glandular profiles and limited mucin production (Figure 53). Diffuse staining for neuron-specific enolase and dotlike perinuclear staining for cytokeratin were present, with sparse reactivity for synaptophysin, neurofilaments, and glial fibrillary acid protein, but with no staining for -fetoprotein or S100 protein. Electron microscopy showed epithelial differentiation with a distinct basal lamina and discrete cell junctions. A diagnosis of medulloepithelioma was made. Inguinal and subcutaneous metastases developed 3 months later, and the patient was started on chemotherapy. She became disease free but died at home of unknown causes 11 months following diagnosis. Peripheral medulloepitheliomas are extremely rare neoplasms and may sometimes be misclassified as other tumors of neuroectodermal derivation, such as primitive neuroectodermal tumors. Some peripheral medulloepitheliomas may be sensitive to chemotherapy with relatively favorable prognosis. Recognition and proper classification of these rare tumors is essential for better understanding of their biology and clinical behavior and for determination of optimal therapy.

Unilateral Orbital and Uveal Metastasis as an Initial Presentation of Adenocarcinoma of Lung

(Poster No. 28)

Payam Arya, MD1 (payamarya@gmail.com); Behrouz Shamloo, MD2; Wanghai Zhang, MD1; Lekidelu Taddesse-Heath, MD1; Eslam Ali, MD.1 Departments of 1Pathology and 2Internal Medicine, Howard University Hospital, Washington, DC.

We present a case of a 41-year-old woman with a history of smoking who presented with left eye pain and redness. Eye examination showed chronic retinal detachment and a mass in the infratemporal area of the left retina. Radiologic workup revealed a hyperdense mass of left globe and a large heterogenous mass in lower lobe of left lung. Left lung biopsy revealed invasive moderate to poorly differentiated adenocarcinoma. Palliative left eye enucleation was performed. In gross pathologic examination, there was a tan, nonhomogenous, brittle, tumoral mass occupying posterior aspect of the globe and extending anteriorly to involve two thirds of the globe. Microscopically, the lesion was a moderately differentiated mucin-producing adenocarcinoma that involved the optic nerve, retina, choroid plexus, sclera, extraocular muscles, and adipose tissue. Neoplastic cells were positive for cytokeratin 7 and thyroid transcription factor 1 and were negative for cytokeratin 20, which is consistent with metastatic adenocarcinoma from lung primary. Lung cancer is the most frequent primary origin of ocular metastasis. The most common site of metastasis in eye is uveal tract (91%). Metastatic cancer affects nearly every ocular tissue, including retina, choroid, cilliary body, and optic nerve. Metastasis to the orbit is less common; metastasis to the optic nerve is relatively rare. Our patient had simultaneous orbital and ocular metastasis, which is extremely rare. This case illustrates that in any patient who is a smoker presenting with retinal detachment and intraocular mass, lung cancer should be strongly considered, even if the patient has no systemic evidence of metastatic disease.

An Image-Sharing Web Site for Pathologists With Integrated "Social Computing" Features

(Poster No. 29)

Kenneth E. Youens, MD (kenneth.youens@duke.edu); John A. Papalas, MD; Michael B. Datto, MD, PhD. Department of Pathology, Duke University Medical Center, Durham, NC.

Context: A recent trend in Web design is to facilitate collaboration and content sharing among users. This trend de-emphasizes the role of the Web as a simple information source, and instead promotes the idea of the Web as a collaborative workspace in which user participation adds value to a site's content. Because collaborative discussion of slides is a primary method of pathology consultation and education, these virtual workspaces are a natural fit as a pathology teaching and discussion tool.

Design: Using ASP.net and Microsoft SQL, our group created www.pathologypics.com (viewable online), an intuitive image-sharing application with collaborative features like image "tagging," commenting, and ratings. Users upload their own images and retain the freedom to share and reuse images uploaded by other users. Rather than categorizing images in a traditional top-down hierarchical catalog based on organ system or disease, users "tag" images with keywords, creating "folksonomies" that result in an organic, easily searchable, bottom-up categorization of the site's content. Users can then comment on and rate the shared images.

Results: Pathology residents at our institution have been using this application for 1 year. Hundreds of images have been uploaded, including images of surgical pathology "unknown" cases, and many images have been extensively discussed online. The commenting feature allows the consultation and education that typically occurs at the microscope to take place online, where the discussions are also available to future users.

Conclusions: Use of image sharing and "social computing" Web tools can be a useful and engaging supplemental resource for pathology education and consultation.

Legal Aspects of Laboratory Medicine for Residents and Fellows: A Curriculum for Pathology Program Directors

(Poster No. 30)

Angela J. Wood, MD1 (wood.angela@mayo.edu); Kimberly K. Otte, JD2; Sharon C. Zehe, JD2; Brad S. Karon, MD, PhD1; James S. Hernandez, MD.1 Department of 1Laboratory Medicine and Pathology and 2Mayo Clinic Legal Department, Mayo Clinic, Rochester, Minn.

Context: Preparing residents and fellows to manage laboratories and pathology practices requires an increasing awareness of the law. Trainees in laboratory medicine and pathology need a framework within which to identify and manage legal risks in dealing with compliance, malpractice, and human resources problems. We describe a curriculum for residents and fellows that highlights activities most likely to result in adverse legal outcomes and helps trainees understand when the services of an attorney may be required.

Design: This 2-hour course was part of a comprehensive Leadership and Management Curriculum designed to help meet the system-based practice and professionalism requirements of the American College of Graduate Medical Education. Didactic lectures and interactive case scenarios were presented, and participants evaluated the course content and speakers. Short-term knowledge accumulation was assessed by comparison of performance between junior and senior residents on the laboratory administration section of the residency in-service examination.

Results: The course was evaluated on a 5-point scale by 53 trainees during a 4-year period (2004-2007), with a mean overall rating of 4.4 (range, 3.5-4.7). Senior residents had a mean (±SD) score on the laboratory administration section of the residency in-service examination of 526 ± 37 over the same time period, compared with their junior resident peers, who scored 459± 46 (P = .02).

Conclusions: This 2-hour module has improved the skills and knowledge of potential laboratory medical directors to prepare them to lead complex medical laboratories. This course can be modified to meet the local needs of other pathology and laboratory medicine training programs.

Critical Results (Diagnoses) in Anatomic Pathology: A College of American Pathologists Survey of 1130 Laboratories

(Poster No. 31)

Raouf E. Nakhleh, MD1 (Nakhleh.Raouf@mayo.edu); Rhona Souers, PhD2; Richard W. Brown, MD.3 1Department of Pathology, Mayo Clinic, Jacksonville, Fla; 2Department of Biostatistics, College of American Pathologists, Northfield, Ill; 3Department of Pathology, Memorial Hermann SW Hospital, Houston, Tex.

Context: The Joint Commission on Accreditation of Healthcare Organizations and the College of American Pathologists have emphasized improved communication as a strategy to improve patient safety and reduce errors. Conveying critical results is a key component of these efforts. A survey was performed to understand the current state of laboratory policies and practices concerning critical results in anatomic pathology.

Design: A survey was distributed with the 2007 D mailing of the Performance Improvement Program slides. The survey included questions that determined laboratory size, practice setting, and anatomic pathology critical result policies and practices.

Results: We received 1868 surveys from 1130 laboratories. Duplicate surveys were eliminated. The median laboratory accessioned 10 000 cases per year. Seventy-five percent had a written policy regarding anatomic pathology critical results; 25% did not. Thirty percent of laboratories stated that their policies included guidelines, but did not include specific examples of critical results. Thirty-three percent listed <5 specific examples, 18% listed 5 examples, and 19% stated that they had a specifically defined list of critical diagnoses. The conditions that were listed as critical results included malignancies (48%), findings not expected by the clinical history (45%), life-threatening infections (45%), no chorionic villi in products of conception (37%), inflammatory or immunologic processes (19%), and organ rejection (14%). Laboratories with higher numbers of specific examples had a higher median number of accessioned surgical cases (P < .001).

Conclusions: This survey illustrates current anatomic pathology critical results policies and practices. While 75% of all laboratories had policies, less than 50% had specifically defined critical results.

Clinical Utility of Immature Neutrophil 1 Flag Generated by the Coulter LH750 Hematology Analyzer at a University Hospital

(Poster No. 32)

Bethany J. Tierno, MD (bethany.tierno@bmc.org); Shveta Arya, MD; Melissa Gallinaro, MT(ASCP); Lija Joseph, MD. Department of Pathology and Laboratory Medicine, Boston Medical Center, Boston, Mass.

Context: The immature neutrophil 1 (immNE1) flag on the Coulter LH750 (Beckman Coulter Inc, Fullerton, Calif) indicates a possible bandemia. Several studies have established the low reproducibility and limited usefulness of band counts in clinical practice. In our laboratory, this flag requires a medical technologist to perform a manual review of the smear and correction of the instrument-generated differential count, if indicated. Approximately 20% of the smears reviewed at the bench are a result of this flag. In this study, we evaluate the clinical utility of this flag in our patient population.

Design: Data from the chart review of 112 sequential immNE1 flags from 99 patients were collected. The peripheral smears were evaluated by the pathologist for significant abnormalities that would have generated an alert to the clinician per established protocols. The patients were categorized based on the clinical diagnosis.

Results: All of the 99 patients (45 males and 54 females; mean age, 53.5 years; range, 0-95 years) fit into 7 categories. Forty patients had an infection, 13 had physical stress (pain or respiratory distress), 14 had inflammatory disease, 13 had a solid tumor, 9 had recent surgery, 6 had recent hemorrhage, and 4 had psychological stress. None of the patients had evidence of acute leukemia, nor was a new diagnosis triggered based on the smear review.

Conclusions: A manual differential and band count following immNE1 from the Coulter LH750 has minimal clinical utility at our institution. Based on these findings, the laboratory will establish process improvement measures to better utilize technologist time.

Challenges and Pitfalls of Morphologic Identification of Fungal Infections in Tissue Sections: A 10-Year Retrospective Review at a Single Institution

(Poster No. 33)

Ankur R. Sangoi, MD1 (asangoi@stanford.edu); William M. Rogers, MD1; Jose G. Montoya, MD2; Teri A. Longacre, MD1; Ellen Jo Baron, PhD1; Niaz Banaei, MD.1 Departments of 1Pathology and 2Medicine (Division of Infectious Diseases), Stanford University Medical Center, Stanford, Calif.

Context: While definitive identification of fungal infections is by culture, surgical pathology is frequently called upon to make intraoperative and permanent section diagnoses, despite the fact that correct histologic classification can be fraught with difficulty.

Design: To assess the accuracy of histologic diagnosis of fungal infections versus culture (gold standard), we performed a 10-year retrospective review (1997 to 2007) at our institution. Of 338 positive mold and/or yeast cultures from tissue, aspirate, abscess, and biopsy samples, 47 cases were identified that had concurrent surgical pathology evaluation and no known history of fungal infection.

Results: Of the 47 study cases, 37 (79%) were correctly identified. The 10 cases (21%) with discrepant diagnoses included the misidentification of Rhizopus (n = 3), Aspergillus spp (n = 2), Scedosporium apiospermum (n= 2), Fusarium (n = 1), Coccidioides immitis (n = 1), and Histoplasma capsulatum (n = 1). Eight (80%) of the 10 discrepancies included errors in division identification, whereas 2 (20%) of 10 involved errors at the genus level. Among these 10 discrepancies, 2 negative clinical consequences resulted: one unnecessary pharmacologic exposure and one delayed treatment without negative effects. The accuracy of histopathology was not related to antifungal therapy (P = .71), not associated with use of special stains (P = .33), not dependent on a provision to correlate and/or defer with culture (P = .99), and not operator dependent.

Conclusions: An accuracy rate of 79% for histopathologic identification of fungal organisms in tissue sections from our institution elucidates potential therapeutic and surgical adverse consequences. As such, challenges and pitfalls are discussed with recommendations for reporting offered.

Referrals for Immunohistochemical Analysis: A Review of 518 Cases

(Poster No. 34)

Augusto Paulino, MD (yorkavenueny@yahoo.com). Department of Pathology, Genzyme Genetics, New York, NY.

Context: The impact of immunohistochemistry in the final interpretation of a case is examined in material received in a reference laboratory.

Design: Cases submitted for immunohistochemical analysis and interpretation were reviewed by a single pathologist. Demographic data (age and sex) as well as body site were compiled. The provisional diagnosis (if provided) and the final interpretation of the cases were compared, and the major and minor discordance rates were calculated. Breast carcinomas submitted for only receptor status staining were not included in this study.

Results: A total of 518 cases were reviewed. There were 224 males and 294 females, with a mean age of 63 years. The most common body sites were as follows: 64 lung cases (12%), 64 lymph node cases (12%), 49 liver cases (9%), and 26 breast cases (5%). In 61 cases, only the results of specific antibodies were requested. Eighteen additional cases did not have a provisional diagnosis. Of the remaining 439 cases, there was a major discrepancy between the provisional and final diagnosis in 22 cases (5%) and a minor discrepancy in 35 cases (8%). The most common cause for referral was determination of the type and/or primary site of carcinoma, and this was answered in 185 (87%) of 212 such cases. Other reasons for referral included the evaluation of lymph nodes for micrometastasis (37 cases) and prostate needle biopsies for carcinoma (20 cases).

Conclusions: Even with the increasing number of technologies available as adjuncts to histopathologic diagnosis, immunohistochemical analysis remains a highly useful tool to pathologists.

Interpretation of Estrogen and Progesterone Receptor Immunohistochemistry May Be Biased by Laboratory Technique and Observer Expertise

(Poster No. 35)

Michael Linden, MD (mlinden1@hfhs.org). Department of Pathology, Henry Ford Hospital, Detroit, Mich.

Context: Estrogen receptor (ER) and progesterone receptor (PR) status plays an important role in the treatment of breast carcinoma. The subjective nature of ER and PR interpretation may lead to inaccurate receptor status and possibly inappropriate treatment.

Design: We studied 100 consecutive cases. Immunohistochemistry interpretation was compared between one pathologist with expertise in immunohistochemistry (EP) and 10 general pathologists (GP). Immunohistochemistry was graded positive, negative, or focal positive (focal staining or weak staining intensity). Immunohistochemistry slides were reviewed independently and recorded.

Results: There was 91% agreement for ER and PR. Both observers found 21 ER and 27 PR cases to be negative. There were 18 discrepancies for ER: 4 cases were negative by GP but positive by EP. Three focal positive cases by GP were positive by EP. Thus, there were 6 cases with discordance between positive and negative by GP and EP. For PR, there was 96% concordance between positive and negative. Three cases were negative by GP but positive by EP, and 1 case was negative by GP and positive by EP. Five focal positive cases by GP were positive by EP.

Conclusions: Concordance between GP and EP was 94% ER and 96% PR. Similar rates of discordance between negative by GP (4%) and positive by EP (3%) were observed and focal positive by GP (3%) and positive by EP (5%). Subjective interpretation and technical variations may limit accurate quantitation in an inherently qualitative test. Discrepant rates of 4% to 6% may have a clinically significant impact on patient treatment and therefore survival.

Accuracy of Reporting Immediate Frozen Section Diagnosis: A 14-Month Retrospective Review and Recommendations for Quality Improvement

(Poster No. 36)

John J. Nelson, MD, MPH (jjnelson@usouthal.edu); Kimberley V. Patterson, MD. Department of Pathology, University of South Alabama, Mobile.

Context: Quality management standards in pathology aim to reduce error in frozen section practice, and numerous studies detail frozen section diagnostic accuracy. However, no known study examines accuracy concerning intraoperative reporting of frozen diagnoses to surgeons, and no standards specifically address methods of immediate frozen diagnosis reporting. We aim to determine whether errors occurred in reporting frozen section diagnoses, as indicated by degree of correlation between pathologic and operative reports.

Design: Frozen sections performed during a 14-month period were retrospectively reviewed. The wording of frozen section diagnosis in pathology reports was compared with frozen result as stated in operative report; events were classified by degree of correlation. Discrepant cases were assessed for type of change in meaning, contributing factors, and impact on operative management.

Results: Of 303 frozen sections, 60.4% (183) had positive correlation (exact match) or positive with minor difference (no change in meaning), 8.9% (27) had negative correlation (change in meaning), and 30.7% (93) had no mention of frozen diagnosis in operative report. Of negative correlations, none resulted in change from benign to malignant or vice versa. Six consisted of change from suspicious to benign or malignant (Table), and 3 likely resulted in change in operative management.

Conclusions: At our institution, correlation between pathologic frozen section diagnosis and surgical interpretation was not perfect. Rare but potentially significant errors in communication occurred. Possible sources of error and improvement in techniques are discussed. Health care organizations and institutions should institute measures to assess and improve methods of immediate reporting of frozen section diagnoses.

Hemolytic Blood Samples: Influence of Obesity and Comorbidity

(Poster No. 37)

Aditya Raghunathan, MD (araghun1@hfhs.org); Bruce A. Jones, MD; Azadeh Stark, PhD. Department of Pathology & Laboratory Medicine, Henry Ford Hospital, Detroit, Mich.

Context: Blood hemolysis constitutes a principal cause of errors in the preanalytic phase of laboratory medicine. In a previous study, we reported a higher prevalence of hemolyzed blood specimens among African Americans as compared with other racial/ethnic groups. We implemented a pilot project to investigate the patients' anthropometric characteristics and comorbidities as potential factors contributing to the rejection of blood specimens due to hemolysis.

Design: Demographic and clinical data were retrieved for 204 consecutive cases that were identified from the laboratory information system databases. Obesity was assessed in body mass index (weight in kg/height in m2), and coexisting illnesses and their level of severities were scored using the Charlson comorbidity index. Statistical analyseswere performed using SAS software (SAS Institute Inc, Cary, NC).

Results: Of 204 patients with hemolyzed blood specimens, complete data were available in 193 cases. Weight and height data were available for 87 African American patients, of whom 32 (37%) had a body mass index of ≥30 (obese or morbidly obese), and 56 non-African American patients, of whom 24 (42%) had a body mass index of ≥30. The different prevalence of obesity and extreme obesity between the 2 groups approached statistical significance (P = .09). Hypertension, malignant neoplasia, and diabetes mellitus were the most prevalent comorbidities, with no significant difference between the groups.

Conclusions: In seeking alternatives other than race for our previously demonstrated higher incidence of hemolyzed blood specimens in African American patients, these preliminary data do not support obesity or comorbidities as an alternative explanation.

Vancomycin-Dependent Immune Thrombocytopenia as a Serologically Demonstrated Anamnestic Response

(Poster No. 38)

Barton Kenney, MD (barton.kenney@yale.edu). Department of Laboratory Medicine, Yale University School of Medicine, New Haven, Conn.

Drug-dependent immune thrombocytopenia is a rare complication of vancomycin therapy. Generally, significant exposure (8 days on average) is required for immune sensitization. However, exceptional cases of precipitous thrombocytopenia have been noted within 24 hours of starting treatment. This is usually explained by prior drug exposure and sensitization. A second hypothesis invokes naturally occurring autoantibodies with weak affinity for platelet surface antigens that develop increased antigenic affinity in the presence of vancomycin. We report the case of a 61-year-old man receiving vancomycin and ceftazidime for lower extremity gangrene who experienced a profound drop in platelet count from 635 000/µL to 3000/µL within 14 hours of antibiotic exposure (Figure 54, Platelet Count vs Time; arrows indicate platelet transfusion; triangles, immunoglobulin infusion). Other cell counts were stable, and the platelet count was repeatedly confirmed. Laboratory studies for disseminated intravascular coagulation were negative, and heparin-induced platelet antibodies were absent. There was no evidence of splenomegally. Preantibiotic and postantibiotic serum samples were preserved and subjected to flow cytometric drug-dependent platelet antibody analysis. The preexposure specimen revealed IgG vancomycin-dependent platelet antibodies, whereas the postexposure specimen demonstrated both IgG and IgM antibodies. Ceftazidime-dependent platelet antibodies were not identified. Vancomycin was discontinued, and the condition rapidly resolved. This is the first report of vancomycin-dependent immune thrombocytopenia with preexposure and postexposure serology findings. This also represents the most rapidly progressive case described thus far in the literature. The presence of preformed IgG and the emergence of IgM support an alloimmune pathophysiology secondary to undocumented prior exposure rather than an autoimmune process.

Monitoring for Undertransfusion of Red Blood Cells

(Poster No. 39)

James V. Hartel, MD1 (jhartel@hsc.wvu.edu); Paul H. Hartel, MD2; Patricia Canfield, MD1; Peter L. Perrotta, MD.1 1Department of Pathology, West Virginia University, Morgantown; 2Department of Pathology, Davis Memorial Hospital, Elkins, WVa.

Context: The purpose of blood utilization review is to monitor transfusion practices. Utilization activities typically focus on ensuring that patients receive the correct type and amount of a blood product. However, transfusion committees are also concerned about overly restrictive blood transfusion policies. The major objective of this study was to determine the incidence and consequences of, as well as the reasons for, withholding red cell transfusions.

Design: A computer algorithm designed in a laboratory information system was utilized to identify patients with hemoglobin less than 7 g/dL who were not transfused with red blood cells (RBCs). Patient charts were examined to categorize reasons for restricting RBC transfusion and to detect any related adverse events.

Results: During a 12-month period, 594 patients with hemoglobin levels less than 7 g/dL (mean, 6.1 g/dL) received 4476 individual RBC transfusions. Ninety-three patients (16%; 40 males and 53 females; mean age, 44 years) did not receive an RBC transfusion. Eighty-six patients (92%) had documented reasons why transfusion was restricted. These included pregnancy, stable anemia, supplementation, laboratory errors (falsely decreased hemoglogin), and patient refusal. The reason for nontransfusion could not be determined in only 7 (8%) of the nontransfused patients. Adverse consequences of nontransfusion were not identified.

Conclusions: This study shows that although RBC transfusion restriction is not rare, there are usually valid reasons for withholding transfusion, and a restrictive policy is safe. For these reasons, and because of the inherent difficulties in identifying nontransfused patients, the rationale for auditing undertransfused patients should be reconsidered.

Unique Case of Cold Agglutinin Autoimmune Hemolytic Anemia

(Poster No. 40)

Phillip E. Starshak, MD (phillip.starshak@ucdmc.ucdavis.edu); Michelle McNamara, MD; Kim Janatpour, MD; Paul Holland, MD; Denis Dwyre, MD. Department of Pathology, University of California Davis Medical Center, Sacramento.

Cold agglutinin autoimmune hemolytic anemia secondary to infection is an uncommon cause of severe hemolytic anemia in children. Florid erythrophagocytosis by neutrophils in the peripheral blood is also a rare documented finding in severe hemolytic anemia. We report a case of a 2½-year-old boy presenting with severe jaundice, dark urine, and hemoglobin of 3.4 g/dL with a history of a recent upper respiratory illness. The blood smear showed clumping of red blood cells and erythrophagocytosis by neutrophils. Red blood cell antibody screen and panel were nonreactive, and the autocontrol showed very weak agglutination. A direct antiglobulin test was negative for IgG and positive for complement. Testing the serum with cord cells showed 1+ agglutination, which is consistent with an anti-i antibody. Serologic testing also showed evidence of acute Epstein-Barr virus infection. Cold agglutinin autoimmune hemolytic anemia caused by anti-i antibody is a rare disease that can be caused by Epstein-Barr virus infection, but the former only rarely causes severe hemolytic anemia. The observance of erythrophagocytosis by neutrophils in the peripheral blood has not been documented with this form of cold agglutinin autoimmune hemolytic anemia. Additionally, routine blood bank testing may easily miss an anti-i antibody if it does not include cord cells on the panel. However, with the patient's clinical history, peripheral blood findings, and positive direct antiglobulin test with complement, cold agglutinin hemolytic anemia should be strongly entertained and should lead to additional testing of patient's serum with cord cells.

Evaluation of Acticlot dPT Assay in Detecting Lupus Anticoagulant

(Poster No. 41)

Tarek Hammour, MD1 (thammou1@hfhs.org); Sundara B. K. Raman, MD1; Philip Kuriakose, MD.2 Departments of 1Pathology and Laboratory Medicine and 2Hematology/Oncology, Henry Ford Hospital, Detroit, Mich.

Context: Lupus anticoagulant (LA) is an antiphospholipid antibody (APA) commonly found in patients with systemic lupus erythematosus and primary antiphospholipid antibody syndrome. APAs are characterized by their ability to prolong clotting times of coagulation-based in vitro tests. Due to the heterogenous nature of the pathologic APA, it is recommended to use at least 2 different LA assays plus a mixing study with pooled normal plasma to determine their presence. Acticlot dPT assay (ACTICLOT, American Diagnostica Inc, Stamford, Conn) has recently been proposed to increase the efficiency of detecting LA.

Design: During the study period (May 2006-October 2007), our existing LA panel, which includes aPTT, dilute Russell viper venom test, and hexagonal phospholipid neutralization, was performed on plasma samples from patients clinically suspected of having an LA. ACTICLOT was perfomed according to the manufacturer's protocol on the same samples. Plasma samples from patients with known LA were used as positive controls. For the negative controls, plasma samples with negative LA panel were used.

Results: A total of 520 patient samples were tested. The existing LA panel detected the presence of LA in 47 samples (9%). ACTICLOT detected LA in 22 (46.8%) of those samples, rendering a false-negative rate of 53.2%. ACTICLOT was also positive in 15 samples in which the LA panel was negative, resulting in a false-positive rate of 3.1% (15/473).

Conclusions: Our results suggest that ACTICLOT does not improve the ability of the current testing methodology in detecting LA in clinically suspected patients.

Fatal Granulomatous Amebic Encephalitis Caused by Group II Acanthamoeba Species in a Human Immunodeficiency Virus-Infected Child

(Poster No. 42)

Sreelakshmi Ravula, MD1 (sravula@usouthal.edu); Mary Mancao, MD2; Elliot Carter, MD.1 Departments of 1Pathology and 2Pediatrics, University of South Alabama, Mobile.

Amebic encephalitis is a rare opportunistic infection in immunocompromised individuals. We report a case of fatal granulomatous amebic encephalitis in a human immunodeficiency virus (HIV)-infected child. An 8-year-old African American girl who was diagnosed with HIV infection at 1 year of age (mother refused HIV testing) was admitted to our institution with fever and complaints of generalized headache. Upon hospital admission, her HIV ribonucleic acid level was 666 380 copies per mL, and absolute CD4^sup +^ cell count was 0 cells per µL; she had been noncompliant with her antiretroviral medication regimen. A computed tomographic scan of the brain on admission revealed a 7-mm enhancing lesion with surrounding edema in the right temporal area. She was started on intravenous vancomycin, ceftazidime, amphotericin, and oral sulfadiazine and pyrimethamine. Subsequent laboratory workup was negative for antigens to Toxoplasma, cytomegalovirus, Histoplasma, and Cryptococcus spp. Blood cultures were negative for aerobic, anaerobic, fungal, and mycobacterial pathogens. During the second week of hospitalization, the patient developed focal seizures and altered mental status. She experienced further neurologic deterioration and died. The postmortem diagnosis was group II Acanthamoeba-induced granulomatous amebic encephalitis. This is the third reported case of Acanthamoeba-related granulomatous amebic encephalitis in an HIV-infected child. The Table summarizes the clinical aspects of the 3 cases. The current case represents a rare but extremely clinically important opportunistic infection in the setting of pediatric immunosuppression.

Evaluation of a Physician Notification Program Using Abnormal Estimated Glomerular Filtration Rates as Part of a Payor-Designed Disease Management Program

(Poster No. 43)

Gary Assarian, DO, FCAP1 (pathman98@yahoo.com); Azadeh Stark, PhD2; Aprille Karlavage, BBA.3 1Department of Pathology/Informatics Administration, Henry Ford Hospital/PLM Inc, Southfield, Mich; 2Department of Pathology and Biostatistics, Henry Ford Hospital, Detroit, Mich; 3Department of Informatic Administration, Professional Laboratory Management, Southfield, Mich.

Context: Studies have shown that the identification of patients with chronic kidney disease is enhanced by reporting estimated glomerular filtration rate. A statewide laboratory network, the Joint Venture Hospital Laboratory group, initiated a novel program to assist in the identification and management of patients with chronic kidney disease. Our study evaluated the impact on and the acceptance of this notification program by clinicians.

Design: Physicians for whom patients had an estimated glomerular filtration rate less than 60 mL/min/1.73 m2 were notified by a separate letter. The notification form also included information regarding the National Kidney Foundation and the plan's guidelines. A questionnaire was designed to evaluate the value of the notification program to clinicians.

Results: A total of 107 (7%) of 1570 surveys were returned. Sixty-four respondents (60%) indicated that they had received the notification letters. The clinicians were asked not to discuss the questionnaire with their clinical staff (Table).

Conclusions: The data strongly indicate that a notification program that reminds physicians of abnormal estimated glomerular filtration rate results and National Kidney Foundation practice management guidelines is extremely valuable to physicians. Ninty-three percent of respondents felt that there was value in our physician education and patient notification program. Our study indicates that this information is an opportunity to provide desired disease management assistance to clinicians. Our evaluation and interest in this area will continue with further study.

Atypical Squamous Cells of Undetermined Significance and Sign-Out Time: One More Determining Factor?

(Poster No. 44)

Kausar J. Jabbar, MD (kausar.jabbar@stjohn.org); Chady Meroueh, MD; Basim Al Khafaji, MD. Department of Pathology & Laboratory Medicine, St John Hospital and Medical Center, Detroit, Mich.

Context: Variability in the rate of atypical squamous cells of undetermined significance (ASC-US) among different cytopathologists and cytotechnologists remains a frustrating dilemma. The perception has been that variations in the day of week and time of day and seasonal time changes and their relation to fatigue may adversely affect the ASC-US rate.

Design: Our study consisted of 2 groups of consecutive Papanicolaou tests: 2081 tests were performed between June 2 and 10, 2005, and 1395 tests were performed between January 4 and 12, 2006. Review of the computer records included signing cytopathologists, reviewing cytotechnolgists, screening diagnosis, final diagnosis, and screening/final diagnosis time and day. The screening/final diagnosis time included 3 time frames: morning (7:00 AM-11:00 AM), afternoon (11:01 AM-4:00 PM), and evening (4:01 PM-6:59 AM).

Results: While there was a fluctuation in the ASC-US rate for both the cytopathologists and cytotechnologists among the different time frames, it was not statistically significant. This included the ASC-US rate in June versus January (P = .48), day of the week (P = .66), and time frame (P = .68) (Table).

Conclusions: While the study does confirm the variability of the ASC-US rate among reporting cytotechnologists and cytopathologists, it refutes the effects of variations in the day of the week, time of day, or season on the ASC-US rate by the absence of a statistically significant difference. Furthermore, this study indicates that flexibility in scheduling review and sign-out times for Papanicolaou tests should not have a negative impact on the ASC-US rate.

Accepted for publication May 19, 2008.

Reprints not available.

© 2008 College of American Pathologists Provided by ProQuest LLC. All Rights Reserved.

Source: Archives of Pathology & Laboratory Medicine

 

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