NASAL T-CELL LYMPHOMA CAUSALLY ASSOCIATED WITH EPSTEIN-BARR-VIRUS - CLINICOPATHOLOGICAL, PHENOTYPIC, AND GENOTYPIC STUDIES

BACKGROUND. The authors have previously demonstrated nasal T-cell lymp homa (NTL) associated with Epstein-Barr virus (EBV). The detailed clin ical, phenotypic, and genotypic features and the role of EBV in lympho magenesis remain to be clarified. METHODS. The study group consisted o f 18 patients with NTL. The phenotype was determined by immunoperoxida se staining with various monoclonal antibodies. Genotypic study was do ne using Southern blot hybridization. The presence of EBV-encoded smal l nuclear early region (EBER) RNA and EBV DNA were determined by in si tu hybridization. The expression of EBV-encoded nuclear antigen (EBNA) and latent membrane protein (LMP1) were identified by immunohistologi c methods. Clonotypic analysis of EBV genomes was performed by Souther n blot hybridization with EBV termini fragment probe. RESULTS. The cli nical features of NTL were characterized as prolonged fever (16 patien ts), widespread dissemination into distant sites (13 patients), and po or prognosis with a median survival of only 6 months. EBER transcripts were identified in 16 of 18 patients. Monoclonal EBV genomes EBNA1 an d LMP1 were also detected in all EBER-positive cases tested. All 18 pa tients expressed pan-T antigens such as MT1, CD45RO, and/or CD2. The r earrangements of T-cell receptor (TCR)-beta, -gamma, and/or -delta gen es were shown in all 11 patients tested. The natural killer (NK) cell phenotype CD56 was expressed in all EBV-positive cases tested, and was not detected in EBV-negative cases. Seven EBV-positive cases expresse d a TCR-delta chain with rearranged TCR-gamma or -delta genes whereas both EBV-negative cases corresponded to alpha beta T-cell lymphoma, wh ich expressed a TCR-beta chain with a rearranged TCR-beta gene. CONCLU SIONS. These data suggest that EBV-positive NTL may be derived from th e lineage of NK-like T-cells or gamma delta T-cells, and that EBV may play a role in lymphomagenesis. Therefore, we propose that NTL which h as peculiar clinical and histologic features, could be classified as a new lymphoma entity. (C) 1996 American Cancer Society.