Henry Y. Dong

CD5- mantle cell lymphoma.

Mantle cell lymphoma (MCL) typically expresses B-cell antigens and CD5 and overexpresses bcl-1 protein. However, unusual cases of bcl-1+ and CD5-MCL have been observed, posing a practical challenge for correct diagnosis and management. We identified 25 cases (48 samples) of bcl-1+ and CD5- lymphoma. CD5 expression was assessed by flow cytometric analysis alone (1 case), immunohistochemical analysis alone (17 cases), or dual flow cytometric/immunohistochemical methods (7 cases). The morphologic features were consistent with MCL with centrocytic cytomorphology in 20 cases and blastic variant in 5 cases. The t(11;14) was confirmed in 8 of 11 cases by fluorescence in situ hybridization of paraffin-embedded tissue. Cytogenetic analysis revealed the t(11;14) within a complex karyotype in 2 additional cases. These data show that MCL may lack CD5 expression. Evaluation of bcl-1 expression by immunohistochemical analysis or molecular genetics may be indicated if MCL is suspected clinically or morphologically despite a lack of CD5 expression.

B-Cell Lymphomas With Coexpression of CD5 and CD10

Coexpression of CD5 and CD10 is highly unusual in B-cell lymphomas and may pose a diagnostic challenge. We report 42 cases of B-cell lymphoma with simultaneous expression of CD5 and CD10. They made up approximately 0.4% of all B-cell lymphomas seen during the study period and included the following cases: large B-cell lymphoma (LBCL), 14 (33%); follicular lymphoma (FL), 10 (24%); mantle cell lymphoma (MCL), 9 (21%); chronic lymphocytic leukemia, 4 (10%); acute precursor B-cell lymphoblastic leukemia/lymphoma, 2 (5%); and other low-grade B-cell lymphomas, 3 (7%). All MCLs had overexpression of bcl-1 or the t(11;14) and were CD43+. All FLs had typical histomorphologic features and were bcl-2+ and bcl-6+ but CD43-. Of 14 LBCLs, 5 were histologically high-grade. Six (43%) of 14 patients with LBCL died within 10 months of diagnosis of CD5+CD10+ lymphoma (median survival, 4 months), including all 3 patients with stage IV disease and 2 of 5 with histologically high-grade lymphoma. Our findings indicate that coexpression of CD5 and CD10 is rare but occurs in diverse subtypes of B-cell lymphoma. Investigation of bcl-1, bcl-6, and CD43 and morphologic evaluation may resolve the potential confusion in diagnosis and lead to the recognition of the correct lymphoma subtype.

B-cell specific activation protein encoded by the PAX-5 gene is commonly expressed in merkel cell carcinoma and small cell carcinomas

PAX-5 is a B cell specific transcription factor crucial for B cell ontogeny and has been detected in most of human B-cell lymphomas. In mouse, PAX-5 is also highly expressed in the central nervous system under tight temporal and spatial controls during embryogenesis. In humans, however, detection of PAX-5 in cells other than B lymphocytes has rarely been reported. We have encountered cases of Merkel cell carcinoma expressing PAX-5 during our routine evaluation of lymphoma. Because Merkel cell carcinoma is a small blue round cell tumor constantly in the differential diagnosis of lymphoma, we expanded our study in an effort to determine if PAX-5 is significantly expressed in neuroendocrine tumors. Based on our immunohistochemistry results using a monoclonal anti-PAX5 antibody with paraffin-embedded tissue sections, we report herein that PAX-5 was detected in 29 of 31 (93.5%) of Merkel cell carcinoma and 22 of 30 (73.3%) of small cell carcinoma, but in none of 17 cases of carcinoid tumor. Furthermore, the staining intensity of PAX-5 in Merkel cell carcinoma was frequently comparable with that in most B-cell lymphomas. We conclude that expression of PAX-5 is not confined to the B cell lineage and is frequently associated with neuroendocrine carcinomas.

PAX-5 is invariably expressed in B-cell lymphomas without plasma cell differentiation.

Aims:  The B‐cell‐specific transcription factor PAX‐5 is physiologically expressed in normal B cells and silenced in plasma cells. The aim of this study was to determine whether PAX‐5 expression is universal among B‐cell malignancies.

Human herpesvirus 8- and Epstein–Barr virus-associated solitary B cell lymphoma with a T cell immunophenotype

Two subtypes of human herpesvirus 8 (HHV8)-associated lymphomas are described in the 2008 World Health Organization (WHO) classifi cation of hematopoietic malignancies [1]. Primary eff usion lymphoma (PEL) is a B cell malignancy primarily presenting with malignant serous eff usions in body cavities, without a solid mass. It is characteristically associated with both HHV8 and Epstein – Barr virus (EBV). Th e lymphoma cells exhibit variable plasmacytoid features and express plasma cell antigens MUM1 and CD138, but lack pan B- and T-cell antigens in general. Apart from extracavitary involvement occurring in a typical PEL, PEL-like lymphomas presenting with a tumor mass without eff usion have been termed extracavitary PEL, which is nearly always a disseminated disease. HHV8-associated large B cell lymphoma arising from multicentric Castleman disease (MCD) typically presents as a nodal lymphoma exclusively associated with HHV8, without EBV co-infection. Th e tumor cells express weak CD20 and/or CD79a, lack CD138 expression despite being consistently MUM1 positive, and always express strong cytoplasmic immunoglobulin M (IgM) and are nearly always lambda-restricted. Rare variants of HHV8and EBV-associated B cell lymphoma beyond these two subtypes were reported to only partially or focally involve lymph nodes, such as germinotropic lymphoproliferative disorder [2], Hodgkin-like large B cell lymphoma and intravascular large cell lymphoma [3]. We report an unusual lymphoma originally presenting as a left axillary mass with no eff usions typical of PEL or evidence of disease dissemination. It was characterized by tumor cells uniformly expressing EBV-encoded RNA (EBER) and multiple pan-T cell antigens, including CD3, resembling a rare primary lymph node-based, EBV-associated T/natural killer (NK) cell lymphoma. However, they were also homogeneously HHV8 positive, and its B cell origin was established by detection of a clonal immunoglobulin heavy chain ( IGH ) gene rearrangement in the absence of detectable T cell monoclonality. Th e patient was a 54-year-old man who was diagnosed with human immunodefi ciency virus (HIV) infection 14 years prior to lymphoma work-up and had been on highly active antiretroviral therapy (HAART; lamivudine, zidovudine, efavirenz) for 5 years. He presented with fevers and a new left axillary mass that developed over a 1-month period. His lactate dehydrogenase (LDH) was 485 U/L and the HIV viral load was undetectable. Th e CD4 count was documented to be 114/ μ L two and a half months earlier. A small incisional biopsy of the mass revealed a focal involvement by an EBV T/NK-cell lymphoma based on the immunophenotypic profi le. Th e patient was fi rst treated with antibiotics for a potential infectious process while undergoing additional studies. Th ere was no evidence of MCD, monoclonal gammopathy or bone marrow involvement by lymphoma. A positron emission tomography (PET) scan did not reveal clear evidence of additional lesions. Two months after the initial biopsy, he was admitted for recurrent fevers and enlargement of the left axillary mass. Given the clinical question to the original diagnosis, an excisional biopsy was performed to better diagnose lymphoma and exclude infection. Th e results of all cultures for microorganisms from the biopsy were negative. Th e morphology and immunophenotype of the second biopsy were similar to those of the fi rst, except for total displacement of the normal tissue by tumor cells. Th erefore, the same diagnosis was again considered. During the hospital stay, the patient had fevers, hypotension, hypoalbuminemia and pancytopenia requiring supportive care. He received two cycles of cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) with initial improvement, followed by deterioration. Meanwhile, additional studies for HHV8 and gene rearrangements on the second biopsy led to a diff erent fi nal diagnosis, the patient was transferred to the National Cancer Institute. At the time of his re-evaluation, he was found to have residual lymphoma in the axillary mass, a newly developed large lymphomatous eff usion in the left pleural cavity and advanced Kaposi sarcoma (KS) with tumor-associated edema. KS was diagnosed 5 years earlier, and had never been treated with chemotherapy, although this information was not