原发性中枢神经系统EBV阳性弥漫大B细胞淋巴瘤4例临床病理分析

Primary EBV positive diffuse large B cell lymphoma of central nervous system: a clinicopathological analysis of four cases

目的探讨原发性中枢神经系统(CNS) EBV阳性弥漫大B细胞淋巴瘤(EBV+DLBCL)的临床病理特征和病理诊断。方法对4例原发性CNS EBV+DLBCL的临床病理特点进行回顾性分析,并结合相关文献进行复习。结果 4例患者均为男性,发病年龄30~66岁。3例患者行肿瘤切除术,1例行MRI立体定向活检。镜下肿瘤组织均弥漫片状生长,伴不同程度坏死。其中3例可见肿瘤细胞围绕血管形成套袖状结构,部分区域血管破坏。肿瘤细胞中等偏大,形态单一,主要由中心母样和/或免疫母样细胞构成。免疫组织化学肿瘤细胞CD20、Bcl-2(+),CD3、CD5(-),Ki-67阳性率70%~80%。值得注意的是,3例为non-GCB型,1例为GCB型。EBER原位杂交均(+),其中3例EBNA2(+),分子检测无MYD88突变及C-MYC重排;另一例因组织极小无法进行EBNA2和分子检测。4例患者随访1~26个月,2例死亡,1例复发,另外1例目前无复发或其他部位累及。结论原发性CNS EBV+DLBCL是罕见的恶性肿瘤,本组原发于CNS的病例除了符合常见EBV+DLBCL诊断标准外,还均有EBNA2(+),提示患者可能存在不同程度获得性免疫缺陷,其确切致病机制是否不同于颅外病变及更确切的分子遗传学特征有待扩大样本进一步研究。

Objective To investigate the clinicopathological characteristics of primary EBV positive diffuse large B cell lymphoma( EBV+ DLBCL) of central nervous system( CNS). Methods The clinicopathological features of 4 patients with primary CNS EBV + DLBCL were carefully analyzed,and related literatures were reviewed. Results All the 4 patients were male,with the onset age ranging from 30 to 66 years. Three patients underwent tumor resection and one had stereotactic biopsy. Microscopically,the tumors were hypercellular and diffusely distributed with different degrees of necrosis. The perivascular cuffs were seen in 3 cases and various degree of vascular destruction was identified. The tumor cells were monomorphic atypical lymphoid-like cells with size of medium to large and mainly showed centroblast or immunoblast morphology. The tumor cells were positive for CD20 and Bcl-2 but negative for CD3 and CD5;Ki-67 proliferation index was 70% ~ 80%. Interestingly,three cases were of non-GCB subtype and 1 was of GCB subtype. Tumor cells of all cases were positive for EBER in situ hybridization. EBNA2 was positive in three cases while no MYD88 mutation and C-MYC rearrangement were detected. There was too little tissue to perform EBNA2 and molecular tests for the other case. At a follow-up of 1 to 26 months,two patients died,one recurred and the other one had no recurrence or spread.Conclusions Primary CNS EBV+ DLBCL is a rare malignant tumor. Besides meeting the common diagnostic criteria for EBV+ DLBCL,cases in this group are also positive for EBNA2,suggesting that the patients may have different extent of acquired immune deficiency. Whether the exact pathogenic mechanism is different from extracranial lesions and more precise molecular genetic characteristics need further studies in larger cohorts.