Y. Harabuchi et al., NASAL T-CELL LYMPHOMA CAUSALLY ASSOCIATED WITH EPSTEIN-BARR-VIRUS - CLINICOPATHOLOGICAL, PHENOTYPIC, AND GENOTYPIC STUDIES, Cancer, 77(10), 1996, pp. 2137-2149
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.