Primary mammary lymphoma is rare, and little is known about the immunophenotype of such cases. The authors studied both primary and secondary breast lymphomas with a broad panel of T‐ and B‐cell markers using paraffinembedded tissue and the avidin–biotin immunoperoxidase method. Cases of primary B‐cell lymphoma were further tested to determine light and heavy chain type. Thirty‐five cases were analyzed, including 16 primary lymphomas. Diffuse large cell lymphoma was present in ten of 16 primary and 14 of 18 secondary cases. Lymphoepithelial lesions in ducts and lobules and frequent vascular involvement were found in both primary and secondary cases. Immunohistochemistry studies on 13 tumors revealed all of the primary tumors to be B‐cell in origin, except for one case of primary T‐cell lymphoma; to the authors' knowledge, this represents the first description of this entity. Fifteen of 17 secondary tumors exhibited B‐cell markers and one of 17 exhibited T‐cell markers; in only one case could lineage not be determined. Among primary B‐cell cases, IgM was found to be the most frequent heavy chain type; IgA reactivity was found in only one case. Survival was related to stage and histologic characteristics; patients with Stage II disease and higher grade histologic lesions had a worse prognosis. Half of the patients with primary lymphoma have had recurrent disease. Although local recurrences were observed, the authors also saw a tendency for recurrence in other extranodal sites. The authors conclude that, although primary lymphoma of the breast is compatible with long‐term survival, a significant number of patients eventually die of their disease. As with other extranodal lymphomas, survival rate appears most related to stage of disease. Also, the vast majority of primary tumors are B‐cell in origin, express IgM heavy chain, and can be considered tumors of mucosa‐associated lymphoid tissue.
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.
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.
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.
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