Cyclin D1 protein expression in mantle cell lymphoma
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CD5
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Immunostaining for cyclin D1 is essential for reliable diagnosis of mantle cell lymphoma (MCL). However, a small number of cyclin D1-positive lymphomas other than MCL have been encountered. Our goal was to investigate the morphological spectrum of MCL as a disease entity, based on cyclin D1 overexpression. We reviewed 181 biopsy specimens obtained from 168 cases of cyclin D1-positive MCL. Typical findings were the presence of nodular (53.9% of cases) or diffuse (46.1%) histological patterns, containing mantle zone patterns (16.8%), naked germinal centers (33.5%) and perivascular hyaline deposition (83.2%). Unusual findings of residual germinal centers with a mantle cuff (four cases) and follicular colonization (two cases) were seen. High magnification showed a monotonous proliferation of tumor cells with cytological diversity including small (3.0%), intermediate (43.1%), medium (34.1%), medium-large (13.2%) and large (6.6%) cells. Pleomorphic and blastic/blastoid variants were encountered in 9.6 and 7.2% of cases, respectively. Three cases had foci of cells of considerable size, with a moderately abundant pale cytoplasm resembling marginal zone B cells. Two cases showed an admixture of cells which appeared transformed and mimicked the histology of chronic lymphocytic leukemia/small lymphocytic leukemia. In one, neoplastic mantle zones were surrounded by sheets of mature plasma cells, resembling the plasma cell type of Castleman's disease. An admixture of areas characteristic of MCL and of other larger cells, indicating histological progression or a composite lymphoma, were observed in seven cases. In high-grade lesions of five cases, nuclear staining of cyclin D1 was rarely detected. In our experience, cyclin D1 expression was also found in nine lymphomas other than MCL (five plasma cell myelomas, three Hodgkin's disease and one anaplastic large cell lymphoma). The application of cyclin D1 staining prompted us to recognize the broad morphological spectrum of MCL. MCL can be diagnosed with the application of cyclin D1 immunostaining, if careful attention is given to architectural and cytological features.
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Leukemic B-cell chronic lymphoproliferative disorders (B-CLPD) are a relatively heterogeneous group of diseases, all of which exhibit a clonal expansion of mature-appearing B-lymphoid cells in the peripheral blood (PB). Both primary leukemias and the leukemic phase of primary lymphomas are included in this category (1). Among the primary B-cell leukemias, chronic lymphocytic leukemia (CLL), prolymphocytic leukemia (PLL), and hairy cell leukemia (HCL) are usually considered; within the primary lymphomas, follicular lymphoma (FL), mantle cell lymphoma (MCL), marginal zone splenic lymphoma (MZSL), lymphoplasmacytic lymphoma (LPL), and the large B-cell lymphomas (LCLs) exhibit PB involvement more frequently (1).
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The existence of primary nodal marginal zone lymphomas (MZL) is controversial, as is their relationship to putative extranodal counterparts. Most nodal lymphomas with monocytoid B cell/marginal zone differentiation exhibit the morphologic and immunophenotypical characteristics of extranodal MALT-lymphomas. Splenic marginal zone lymphoma (SMZL) is also of putative marginal zone derivation, but it differs immunophenotypically from MALT lymphoma. To clarify the relationship between nodal and extranodal MZLs and to investigate the possible existence of a nodal variant of SMZL, 36 MZL initially considered to be primary nodal neoplasms were examined. Other low-grade lymphomas with marginal zone differentiation were excluded (small lymphocytic lymphoma/chronic lymphocytic leukemia [SLL/CLL], follicular lymphoma, and mantle cell lymphoma). Six nodal MZLs showed morphologic and phenotypic characteristics similar to those of SMZL, whereas 30 tumors were more similar to MALT-type lymphomas. The six tumors with SMZL features showed a polymorphic infiltrate surrounding residual germinal centers with absent or very attenuated mantle cuffs. These lymphomas were IgD positive (6/6) but cyclin D1 (0/5), CD5 (0/6), and CD23 (0/6) negative. Five of these patients came for treatment in stage I or II. No patient manifested splenomegaly, peripheral blood, and/or bone marrow infiltration either at diagnosis or during follow-up. Lymph nodes from 30 patients with MALT-type features showed a perisinusoidal and perivascular infiltration of monocytoid/centrocytoid cells and residual germinal centers with a relatively well-preserved mantle cuff. The neoplastic cells were negative for IgD (0/17), cyclin D1 (0/8), and CD5 (0/12). Seven of 16 (44%) patients with a detailed history and clinical follow-up had evidence of extranodal lymphoma. These observations suggest that most nodal B cell lymphomas with marginal zone differentiation are of the MALT type and that they are frequently associated with an extranodal component. In addition, a primary nodal counterpart of splenic MZL also exists, and may occur in the absence of splenomegaly.
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Lymphoplasmacytic Lymphoma
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This issue of the journal includes an important study by Sandes et al. (1), which explores whether inclusion of analysis of CD200 expression can contribute to improved classification of mature B cell neoplasms (MBN). Currently, the most frequent subgroupings used for classification purposes are (2,3): CD5+CD10− [(chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL)]; CD5−CD10+ [Follicular lymphoma (FL), diffuse large B cell lymphoma (DLBCL), and Burkitt’s lymphoma]; and CD5−CD10− [marginal zone lymphoma (MZL), lymphoplasmacytic lymphoma, and lymphomas with hairy/villous cells including splenic marginal zone lymphoma (SMZL), and hairy cell leukemia (HCL)].
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The distinction between mantle cell lymphoma (MCL) and other low-grade B-cell neoplasms is important because MCL has a more aggressive clinical course. In bone marrow biopsy specimens, this distinction can be especially difficult. We examined 70 bone marrow biopsy specimens involved by various B-cell lymphoid neoplasms to assess the utility of cyclin D1 immunostaining in distinguishing MCL from other B-cell lymphoproliferative disorders. We used a cocktail of two monoclonal anti–cyclin D1 antibodies and a heat- and sonication- induced epitope retrieval procedure. The neoplasms assessed included MCL (32 cases), small lymphocytic lymphoma/chronic lymphocytic leukemia (18 cases), follicular lymphoma (11 cases), hairy cell leukemia (5 cases), splenic marginal zone lymphoma (2 cases), and small lymphocytic lymphoma with plasmacytoid differentiation (2 cases). The diagnosis of MCL in bone marrow was confirmed by review of the original diagnostic biopsy specimens along with additional data, such as immunophenotypic or molecular studies. Most MCL (23/32; 72%) cases expressed cyclin D1 protein. In contrast, one case of small lymphocytic lymphoma/chronic lymphocytic leukemia (1/18; 6%) and one case of hairy cell leukemia (1/5; 20%) expressed cyclin D1 protein. These findings demonstrate that immunostaining for cyclin D1 protein expression is useful in distinguishing MCL from other B-cell lymphoid neoplasms in the bone marrow.
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PURPOSE: CD5 is a T cell marker, aberrantly express in B cell chronic lymphocytic leukemia (B-CLL) and mantle cell lymphoma (MCL). Other chronic B cell malignancies including hairy cell leukemia (HCL) and B cell prolymphocytic leukemia (B-PLL) are CD5 negative or express this antigen in a weak way. In this study, CD5 expression was investigated in leukemic cells from 42 patients with chronic B cell lymphoproliferative disease. METHODS: We studied the CD5 expression in leukemic cells from 42 patients with chronic B-cell malignancies by flow cytometry. Demographic features such as age, sex and clinical date were also analyzed. RESULTS: There were 22 males and 20 females. The immunophenotyping showed that 35 cases were B-CLL, 3 B-PLL and HCL and one patient was MCL. CD5 expression was present in all B-CLL and MCL. Low expression of CD5 was observed in one patient with B-PLL and negative in all cases of HCL. CONCLUSION: Our date demonstrated that CD5 expression can help distinguish among B-CLL from HCL and B-PLL, but is similar expressed in MCL.
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Prolymphocytic leukemia
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