IMMUNOLOGICAL AND EPSTEIN-BARR VIROLOGICAL STUDIES OF LETHAL MIDLINE GRANULOMA

本文对18例致死性中线肉芽肿型鼻t细胞淋巴瘤（NTL-LMG）的临床表型和基因型特征及其与eb病毒（EBV）的关系进行了研究。临床特征为持续发热（16例），广泛传播至远处（13例），预后差，中位生存期仅6个月。18例患者中有16例发现ebv编码的小核早期区（EBER）转录本。在所有eber阳性病例中均检测到EBV单克隆基因组、EBV编码核抗原1型（EBNA1）和潜伏膜蛋白1型（LMP1）。所有18例患者均表达泛t抗原，如MT1、CD45RO和/或CD2。t细胞受体(TCR)- β， - γ和/或- δ基因的重排在所有11个测试的肿瘤中均显示。自然杀伤（NK）细胞表型CD56在所有ebv阳性病例中表达，而在ebv阴性病例中未检测到。7例ebv阳性表达tcr - δ链，tcr - γ或- δ基因重排。2例ebv阴性均为字母细胞淋巴瘤，为tcr - β链，tcr - β基因重排。这些数据提示EBV阳性NTL-LMG可能来源于nk样t细胞或γ - δ细胞谱系，并且EBV可能在淋巴瘤发生中起作用。因此，我们认为具有特殊临床和组织学特征的NTL-LMG可归类为一种新的淋巴瘤实体。

Clinicalphenotypicand genotypic features and the association with Epstein-Barr virus (EBV) of 18 patients with nasal T-cell lymphoma of lethal midline granuloma type (NTL-LMG) were investigated. The clinical features were characterized as prolonged fever (16 patients), widespread dissemination into distant sites (13 patients), and poor prognosis with median survival of only 6 months. EBV-encoded small nuclear early region (EBER) transcripts were identified in 16 of 18 patients. Monoclonal EBV genome, EBV-encoded nuclear antigen type 1 (EBNA1), and latent membrane protein type 1 (LMP1), were detected also 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 tumors 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 TCR-delta chain with rearranged TCR-gamma or -delta gene. While, all 2 EBV-negative cases corresponded to alphabetaT-cell lymphoma, which represented TCR-beta chain with rearranged TCR-beta gene. These data suggest that EBV-positive NTL-LMG may be derived from the lineage of NK-like T-cell or gammadeltaT-cells, and that EBV may play a role in the lymphomagenesis. Therefore, we propose that NTL-LMG which have peculiar clinical and histological features could be classified into a new lymphoma entity.