EPSTEIN-BARR-VIRUS AND AIDS-RELATED PRIMARY CENTRAL-NERVOUS-SYSTEM LYMPHOMA - VIRAL DETECTION BY IMMUNOHISTOCHEMISTRY, RNA IN-SITU HYBRIDIZATION AND POLYMERASE CHAIN-REACTION

Epstein-Barr virus (EBV) has been implicated in the pathogenesis of ac quired immunodeficiency syndrome- (AIDS) related primary central nervo us system (CNS) lymphoma. Tumors from 16 patients with AIDS-related pr imary CNS lymphoma, and 1 with concurrent CNS and systemic lymphoma, w ere evaluated histologically and for the presence of EBV by immunohist ochemistry for latent membrane protein, in situ hybridization for EBER 1 RNA transcripts, polymerase chain reaction (PCR) for the single cop y EBNA1 gene, and PCR for the multiple copy EBV internal repeat region . Histologically, 11 tumors displayed extremely large, bizarre, anapla stic immunoblasts, with prominent nucleoli and multilobated nuclei, re sembling Reed-Stemberg (RS) cells and variants. The lymphomas displaye d B cell phenotypes by immunohistochemistry. Latent membrane protein w as detected in 88% (15/117) of tumors, EBNA1 sequences in 54% (6/1 1), EBV-internal repeat sequences in 100% (11/11), and EBER1 transcripts in 100% (17/17). All EBNA1-negative tumors lacked RS-like cells. Laten t membrane protein immunohistochemical staining was limited to a minor ity of tumor cells, and was most often positive in RS-like, immunoblas tic large cells. In situ hybridization for EBER1 message demonstrated EBV in the majority of tumor cells, which displayed a wide range of si zes and variable nuclear morphology. We conclude that EBV can be detec ted in all AIDS-related primary CNS lymphomas, and that EBER1 in situ hybridization is currently the best technique for detecting virus. The presence of atypical immunoblasts (RS-like cells) with high levels of latent membrane protein in many of these tumors may suggest the emerg ence of a common, virally-determined phenotype in AIDS-related Lymphom as of brain.