Case of Epstein-Barr virus-associated transformation of mantle cell lymphoma.

We report here a case of mantle cell lymphoma (MCL) in a patient who, following Epstein-Barr virus (EBV) infection, developed diffuse large B-cell lymphoma (DLBCL). A 47-year-old woman was diagnosed as having MCL with clinical stage IIIA in July 1990. After treatment with a third-generation chemotherapy without response, she was kept under observation for 8 years. In January 1999, fever and night sweats appeared with laboratory evidence for EBV infection, and acute swelling of lymph nodes and hepatosplenomegaly developed in May 1999. Histopathological examination confirmed the diagnosis of DLBCL. Sequence analysis of the complementarity-determining region (CDR)-III of the immunoglobulin heavy chain gene demonstrated clonal identity between the initial MCL and the subsequent DLBCL. Immunohistochemistry revealed that cyclin D1, CD5, and CD20 were expressed in the MCL but lost in the DLBCL cells, and EBER-ISH confirmed that EBV infection was absent in the former but present in the latter. Southern hybridization with the EBV terminal repeat probe showed a clear monoclonal pattern in the DLBCL specimen. All these results suggest that EBV infection may have been the molecular event that caused transformation of MCL cell(s) to DLBCL in this case. This is, to the best of our knowledge, the first well-documented case of EBV-associated transformation of MCL.