September 12, 2008

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

By Anonymous

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 Cafe 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


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

(Poster No. 1)

Rebecca M. Wilcoxon, MD ([email protected]); 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-lambda 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 lambda 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 ([email protected]); 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 ([email protected]); 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 ([email protected]); 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 ([email protected]); 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 ([email protected]). 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 kappa 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 ([email protected]); 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/[mu]L). 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 ([email protected]); 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 ([email protected]); 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 ([email protected]); 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 ([email protected]); 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 beta 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 ([email protected]); 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 ([email protected]); 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 ([email protected]); 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 ([email protected]); 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 ([email protected]); 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 kappa 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 kappa light chain (

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

(Poster No. 17)

Summer L. Bohman, MD ([email protected]); 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 ([email protected]). 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 kappa 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 x 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/[mu]L 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 ([email protected]); 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 kappa 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 ([email protected]); 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 Waldenstrom Macroglobulinemia After Long-Term Treatment With Chlorambucil

(Poster No. 21)

Mikako Warren, MD1; Stacey A. Honda, MD, PhD2; Jane H. Uyehara- Lock, MD2 ([email protected]). 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.

Waldenstrom macroglobulinemia is a rare malignant lymphoproliferative disorder with immunoglobulin M monoclonal gammopathy. Chlorambucil, an alkylating agent, is commonly used to treat Waldenstrom 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 4 1/2 years of treatment with chlorambucil for Waldenstrom macroglobulinemia. After 4 1/2 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/[mu]L, 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 Waldenstrom macroglobulinemia.

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

(Poster No. 22)

Syed T. Hoda, MD ([email protected]). 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 ([email protected]); 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 ([email protected]); 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 x 7.0 x 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 ([email protected]); 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 ([email protected]); 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 ([email protected]); 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 ([email protected]); 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 ([email protected]); 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 ([email protected]); 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 ([email protected]); 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 ([email protected]); 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 kappa-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 ([email protected]); 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/[mu]L, a platelet count of 79 103/ [mu]L, 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 bi