DEVELOPMENT OF EPSTEIN-BARR VIRUS-ASSOCIATED B-CELL LYMPHOMA AFTER INTENSIVE TREATMENT OF PATIENTS WITH ANGIOIMMUNOBLASTIC LYMPHADENOPATHY WITH DYSPROTEINEMIA

Evolution of angioimmunoblastic lymphadenopathy with dysproteinemia (A ILD) into aggressive B cell lymphoma is thought to be a rare event and the cause of this transformation has not been fully elucidated. We de scribe two patients with AILD that progressed to aggressive large-cell lymphoma with a B cell phenotype. At presentation, the lymph nodes of both patients showed the typical features of AILD by hematoxylin-eosi n staining. Immunohistochemical staining with monoclonal antibodies re vealed positive staining of atypical cells with UCHL-1 and negative st aining with L-26. In situ hybridization of EBV RNA showed rare positiv e cells in one patient and was negative in the other patient. At relap se, both patients showed systemic lymph nodes swelling, which is chara cteristic of diffuse large immunoblastic lymphoma. Single-cell analysi s with monoclonal antibodies and immunohistochemical staining showed t he monoclonal proliferation of B cells. Southern blot analysis of the lymph nodes showed a rearrangement in both patients of the Ig heavy ch ain gene and germ line configuration of the T cell receptor beta chain gene. Southern blot analysis using the EBV terminal repeat region pro be detected clonal proliferation of EBV in the lymph nodes of both pat ients. In situ hybridization studies identified considerable EBV mRNA in both patients. These observations suggest that EBV proliferation pl ays an important role in the development of B cell lymphoma that arise s from AILD. We suggest that infection or reactivation of EBV may occu r in some patients with AILD, probably due to their immunodeficient st ate, and that this infection or reactivation is directly involved in t he development of B cell lymphoma. (C) 1998 Elsevier Science Ireland L td. All rights reserved.