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Cancer. 1996 May 15;77(10):2137-49.

Nasal T-cell lymphoma causally associated with Epstein-Barr virus: clinicopathologic, phenotypic, and genotypic studies.

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Department of Otolaryngology, School of Medicine, Sapporo Medical University, Japan.



The authors have previously demonstrated nasal T-cell lymphoma (NTL) associated with Epstein-Barr virus (EBV). The detailed clinical, phenotypic, and genotypic features and the role of EBV in lymphomagenesis remain to be clarified.


The study group consisted of 18 patients with NTL. The phenotype was determined by immunoperoxidase staining with various monoclonal antibodies. Genotypic study was done using Southern blot hybridization. The presence of EBV-encoded small nuclear early region (EBER) RNA and EBV DNA were determined by in situ hybridization. The expression of EBV-encoded nuclear antigen (EBNA) and latent membrane protein (LMP1) were identified by immunohistologic methods. Clonotypic analysis of EBV genomes was performed by Southern blot hybridization with EBV termini fragment probe.


The clinical features of NTL were characterized as prolonged fever (16 patients), widespread dissemination into distant sites (13 patients), and poor prognosis with a median survival of only 6 months. EBER transcripts were identified in 16 of 18 patients. Monoclonal EBV genomes EBNA1 and LMP1 were also detected in all EBER-positive cases tested. All 18 patients expressed pan-T antigens such as MT1, CD45RO, and/or CD2. The rearrangements of T-cell receptor (TCR)-beta, -gamma, and/or -delta genes 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 expressed a TCR-delta chain with rearranged TCR-gamma or -delta genes whereas both EBV-negative cases corresponded to alpha beta T-cell lymphoma, which expressed a TCR-beta chain with a rearranged TCR-beta gene.


These data suggest that EBV-positive NTL may be derived from the 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 has peculiar clinical and histologic features could be classified as a new lymphoma entity.

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