EPSTEIN-BARR-VIRUS GENOME IN NON-HODGKINS-LYMPHOMAS OCCURRING IN IMMUNOCOMPETENT PATIENTS - HIGHEST PREVALENCE IN NONLYMPHOBLASTIC T-CELL LYMPHOMA AND CORRELATION WITH A POOR-PROGNOSIS

A series of 520 cases of non-Hodgkin's lymphoma (NHL: 374 of B-cell, 1 30 of T-cell, 5 of non-B/non-T-cell, and 11 of undetermined phenotype) was analyzed for the presence of Epstein-Barr virus (EBV) using RNA i n situ hybridization (RISH). The aims of the study were to assess the frequency of EBV-encoded small nuclear RNAs 1 and 2 (EBER), abundant i mmediate early RNAs (BHLF), and latent membrane protein-1 (LMP-1) in c ases covering the entire histologic spectrum of NHL, and to analyze wh ether EBV status had prognostic relevance with regard to patient survi val. EBER positivity was found in 25 of 374 (7%) B-NHL and 40 of 130 ( 31%) T-NHL (P < .00005) cases, but in only 1 of 16 cases with non-B/no n-T-cell or undetermined phenotype. Among T-NHL cases, EBER positivity was confined to angioimmunoblastic, lymphadenopathy-like lymphoma (11 of 13 cases, 85%), Lennert's lymphoma (five of seven cases, 71%), and pleomorphic T-NHL (24 of 67 cases, 36%). Mycosis fungoides, lymphobla stic, and CD30-positive anaplastic large T-cell NHL cases were consist ently EBV-negative. Double-labeling by RISH and immunophenotyping demo nstrated the presence of EBV in neoplastic T cells, but no CD21 expres sion was found in the EBER-positive T-NHL cases. LMP-1 was expressed i n 12 of 40 (30%) EBER-positive T-NHL and 5 of 25 (20%) EBER-positive B -NHL cases. For both T- and B-NHL, no correlation was found for EBER p ositivity and age, sex, clinical stage, or serum level of lactate dehy drogenase (LDH) at diagnosis. However, in T-NHL but not B-NHL, EBER po sitivity correlated with the presence of constitutional symptoms and a poor performance score (PS > 1; scale, 0 to 4). EBER status did not h ave any prognostic significance in B-NHL, but it had a negative progno stic impact in high-grade T-NHL (7-year survival of EBER-negative v EB ER-positive cases: 33% v 14%; P = .01). A multivariate analysis includ ing all B- and T-NHL of intermediate-/high-grade histology showed that EBER positivity in T-NHL was one of the three most significant factor s recognized by the final prognostic model, only surpassed by PS great er than 1 and age greater than 67 years, and more powerful than B symp toms, an elevated LDH, or disseminated disease (clinical stage greater than II). We conclude that patients with EBV-positive T-NHL have a ve ry poor clinical outcome, that EBV status should be considered as addi tional useful information in the classification of T-NHL, and that EBV -positive T-NHL should be treated as a separate entity in the future. (C) 1996 by The American Society of Hematology.