A Small Subset of CD5-Negative Diffuse Large B-Cell Lymphomas Express Nuclear Cyclin D1 with Evidence of Amplified Cyclin D1 Signals or the t(11;14) Translocation.

Abstract

The expression of cyclin D1 in malignant lymphomas is largely restricted to mantle cell lymphoma, plasma cell myeloma and hairy cell leukemia. In virtually all cases of mantle cell lymphoma and some cases of plasma cell myeloma, the t(11;14) translocation between the immunoglobulin heavy chain and the CYCLIN D1 genes can be demonstrated using fluoroscence in situ hybridization. There are also anecdotal reports of the expression of cyclin D1 in other lymphoma subtypes including small lymphocytic lymphoma, Hodgkin lymphoma and anaplastic large cell lymphoma. In our routine practice, we have encountered a few cases of diffuse large B-cell lymphomas with immunohistochemical evidence of cyclin D1-expression. Therefore, an unselected large number of diffuse large B-cell lymphomas (n=231) from archived material collected at three university hospitals in Sweden were stained for cyclin D1 and microscopically evaluated with regard to cyclin D1-expression. The lymphomas studied included 11 of anaplastic subtype, 4 of immunoblastic subtype, 6 of T-cell/histiocyte rich subtype and the remainder of centroblastic subtype. 10 (4%) of the 231 cases showed nuclear positivity for cyclin D1. 9 of these were of centroblastic subtype and 1 of anaplastic subtype. All of the cyclin D1 positive cases were negative for CD5. The cyclin D1-positive cases were further subjected to fluoroscence in situ hybridization to determine the presence of the t(11;14) translocation. One of these cases (of centroblastic subtype) showed a hybridization pattern consistent with the t(11;14) rearrangement. Two other cases (one of centroblastic subtype and one of anaplastic subtype) displayed a fluoroscence pattern with amplified cyclin D1 signals in the absence of evidence of the t(11;14) translocation, possibly related to CYCLIN D1 gene amplification. Thus, contrary to the current view, there appears to exist a certain number of cyclin D1-positive and CD5-negative diffuse large B-cell lymphomas some of which display amplified cyclin D1 signals or the t(11;14) translocation. The results emphasize the importance of CD5 and cyclin D1 immunostaining in routine diagnostics of diffuse large B-cell lymphomas. Whether CD5-negative cyclin D1-positive lymphomas with the t(11;14) translocation and classic centroblastic morphology should be classified as mantle cell lymphomas or diffuse large B-cell lymphomas remains debatable.

Cyclin D1‐positive diffuse large B‐cell lymphoma

“…More recently, Ehinger et al. have reported in abstract form the immunohistochemical detection of cyclin D1 in 10 (4%) of 231 DLBCLs examined, of which only one carried t(11;14) and might be considered an MCL 10 . Using the sensitive SP4 rabbit monoclonal antibody, we failed to identify any additional cyclin D1+ cases amongst 146 DLBCLs and Burkitt lymphomas chosen to reflect the characteristics of our index case.…”

“…2 Third, the degree of IGHV somatic hypermutation detected was much greater than that seen in all but the most exceptional MCLs, 6 (11;14) and might be considered an MCL. 10 Using the sensitive SP4 rabbit monoclonal antibody, we failed to identify any additional cyclin D1+ cases amongst 146 DLBCLs and Burkitt lymphomas chosen to reflect the characteristics of our index case. Together, our data and those of Ehinger show that rare cases of DLBCL may express cyclin D1 in the absence of a CCND1 translocation, and suggest that detection of a t(11;14)(q13;q32) ⁄ IGH-CCND1 or variant translocation is preferable to immunohistochemical detection of cyclin D1 alone for discrimination between pleomorphic blastoid MCL and DLBCL.…”