单形性亲上皮性肠道T细胞淋巴瘤临床病理特征分析

Monomorphic epithelial intestinal T-cell lymphoma:a clinicopathological characteristic analysis

目的探讨单形性亲上皮性肠道T细胞淋巴瘤(MEITL)的组织病理学形态、免疫表型、分子病理特征、临床预后及治疗等。方法回顾性分析四川金域医学检验中心有限公司2019年3月至2021年2月5例MEITL患者的临床病理资料,并复习相关文献。5例均进行组织病理、免疫组织化学、EB病毒原位杂交及T细胞克隆性评估检测,1例进行了二代测序(NGS)检测。临床随访2例。结果5例MEITL均为中老年男性,组织病理学表现为肠壁弥漫肿瘤细胞浸润,细胞明显亲上皮性。所有患者肿瘤细胞CD3、CD8、CD56、GrB均阳性,其他T细胞标志表达情况不一,其中1例CD30阳性,1例CD20阳性。5例EB病毒原位杂交均阴性。5例均检测到T细胞受体基因单克隆性重排。1例NGS检测到BCOR、JAK3、STAT5B、ATM基因突变。2例获得随访的患者中,1例首次发病行手术后7个月复发,再次手术,13个月后因肺、肝、腹腔广泛转移并腹腔积液死亡;1例穿孔急诊手术后1个月死亡。结论MEITL是一种罕见的消化道原发性T细胞淋巴瘤,发病机制主要涉及肿瘤抑制基因SETD2突变和JAK-STAT通路的1个或多个基因突变。MEITL目前无标准的治疗方法,主要采取手术切除和蒽环类药物为主的化疗。

Objective To investigate the histopathological morphology,immunophenotype,molecular pathological features,clinical prognosis and treatment of monomorphic epithelial intestinal T-cell lymphoma(MEITL).Methods The clinicopathological data of 5 patients with MEITL in Sichuan Jinyu Medical Laboratory Center Co.,Ltd from March 2019 to February 2021 were retrospectively analyzed,and literatures were reviewed.All cases were tested by using histopathology,immunohistochemistry,in situ hybridization of Epstein-Barr virus(EBV)and T-cell clonability assessment,and 1 case had second-generation sequencing(NGS)test.Clinical follow-up was performed in 2 patients.Results All 5 MEITL cases were middle-aged and old men.The histopathology showed that intestinal wall was diffuse with tumor cells infiltrating,and the cells were obviously epitheliophilic.All the tumor cells CD3,CD8,CD56,GrB were positively expressed,and expressions of other T-cell markers were different,among which 1 case had CD30 positive and 1 case had CD20 positive.All 5 cases were negative for EBV by in situ hybridization.Monoclonal rearrangement of T-cell receptor gene was detected in all 5 cases.Mutations of BCOR,JAK3,STAT5B and ATM were detected in 1 case by using NGS.Among 2 cases followed-up,1 patient relapsed 7 months after he had the initial onset and underwent the first operation,and then he had another operation.This patient finally died of extensive metastasis in the lung,liver and abdominal cavity as well as ascites 13 months later;another patient died 1 month after emergency surgery for perforation.Conclusions MEITL is a rare primary T-cell lymphoma of the digestive tract.The oncogenic event in the pathogenesis of MEITL mainly involves mutations in the tumor suppressor gene SETD2 and mutations in one or more genes of the JAK/STAT pathway.Currently,there is no standard treatment for MEITL.Most treatment options include surgical resection and anthracycline-based chemotherapy.