中枢神经系统弥漫性大B细胞淋巴瘤患者临床病理学特征及髓样分化因子88 L265P基因突变分析  

Clinicopathological features and myeloid differentiation factor 88 L265P gene mutation in patients with diffuse large B-cell lymphoma of central nervous system

作　　者：王丹丹[1] 王苗 王雷明[1] 高敏 程磊[3] 谢丽梦 魏宇魁[3] 邹东梅 赵莉红[1] 王伟民 熊艳蕾 滕梁红[1] Wang Dandan;Wang Miao;Wang Leiming;Gao Min;Cheng Lei;Xie Limeng;Wei Yukui;Zou Dongmei;Zhao Lihong;Wang Weimin;Xiong Yanlei;Teng Lianghong(Department of Pathology,Xuanwu Hospital,Capital Medical University,Beijing 100053,China;Department of Pathology,Beijing Friendship Hospital,Capital Medical University,Beijing 100050,China;Department of Neurosurgery,Xuanwu Hospital,Capital Medical University,Beijing 100053,China;Department of Pathology,the First Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou 310003,China;Department of Hematology,Xuanwu Hospital,Capital Medical University,Beijing 100053,China)

机构地区：[1]首都医科大学宣武医院病理科,北京100053 [2]首都医科大学附属北京友谊医院病理科,北京100050 [3]首都医科大学宣武医院神经外科,北京100053 [4]浙江大学医学院附属第一医院病理科,杭州310003 [5]首都医科大学宣武医院血液科,北京100053

出　　处：《中华神经科杂志》2022年第7期682-689,共8页Chinese Journal of Neurology

基　　金：北京市医院管理中心临床医学发展专项(ZYLX202113);首都卫生发展科研专项(首发2020-2-2016)。

摘　　要：目的探讨中枢神经系统弥漫性大B细胞淋巴瘤(DLBCL)患者的临床病理学特征及其髓样分化因子88(MYD88)L265P基因突变情况。方法收集首都医科大学宣武医院于2014年9月至2017年2月诊断的45例中枢神经系统DLBCL患者的病理学标本,分析其临床病理资料,并结合免疫组织化学染色结果、EB病毒原位杂交结果、影像及病史进行回顾性分析,检测MYD88 L265P突变并分析其临床意义。结果 45例患者中男性24例,女性21例,年龄42~82(57.6±8.8)岁。93.3%(42/45)的患者肿瘤累及幕上,呈单发或多发,大脑半球(31/45,68.9%)是最常见的受累部位,21例(21/45,46.7%)病变为多发性病灶。组织学上,中枢神经系统DLBCL表现为肿瘤组织弥漫浸润,部分围绕血管生长,呈"袖套状"排列。免疫表型:所有标本CD20、CD79a均弥漫强阳性,其中39例(39/45,86.7%)为非生发中心B细胞(非GCB)型,6例(6/45,13.3%)为生发中心B细胞(GCB)型。64.4%(29/45)的病例存在MYD88 L265P突变。MYD88 L265P突变的病例在非GCB型(71.8%,28/39)与GCB型(1/6)中所占比例差异有统计学意义(P=0.017)。治疗方式是预后的独立相关因素,与手术/活组织检查(活检)未化学治疗组相比,手术+化学治疗(HR=0.05,95%CI 0.01~0.33,P=0.002)、活检+化学治疗(HR=0.04,95%CI 0.01~0.36,P=0.004)、手术/活检+化学治疗+干细胞移植(HR=0.01,95%CI 0.00~0.17,P=0.001)均能改善生存预后。结论中枢神经系统DLBCL临床表现复杂多样,诊断具有挑战性,预后差。MYD88 L265P是中枢神经系统淋巴瘤常见的基因突变,在非GCB型中的检出率高于GCB型。原发性中枢神经系统淋巴瘤患者化学治疗可明显提高患者生存率,化学治疗达到完全缓解后,行自体造血干细胞移植治疗,可能有机会获得长期生存。Objective To analyze the clinical features and mutation of myeloid differentiation factor 88(MYD88)L265P in patients with diffuse large B-cell lymphoma(DLBCL)of central nervous system(CNS).Methods The clinicopathological materials of 45 cases of DLBCL of CNS were retrospectively collected in Xuanwu Hospital,Capital Medical University from September 2014 to February 2017.The clinicopathological data were retrospectively analyzed,combined with immunohistochemistry,EB virus in situ hybridization,imaging and medical history.The mutation of MYD88 L265P gene was detected by pyrosequencing and its clinical significance was analyzed.Results The age of the patients ranged from 42 to 82 years[(57.6±8.8)years],including 24 males and 21 females.Totally 93.3%(42/45)of the patients had supratentorial tumours,which were single or multiple.The cerebral hemisphere(31/45,68.9%)was the most common involved site,and 21 cases(21/45,46.7%)had multiple lesions.Histologically,DLBCL in the CNS showed diffuse infiltration of tumor tissue,some of which grew around blood vessels in a"sleeve"arrangement.CD20 and CD79a were diffusely and strongly positive.Thirty-nine cases(39/45,86.7%)were non-germinal center B cell(non-GCB)subtype and 6 cases(6/45,13.3%)were germinal center B cell(GCB)subtype.MYD88 L265P mutation was found in 64.4%(29/45)patients.There was statistically significant difference between non-GCB type(71.8%,28/39)and GCB type DLBCL(1/6,P=0.017).Compared with the operation/biopsy group without chemotherapy,operation+chemotherapy,biopsy+chemotherapy,operation/biopsy+chemotherapy+stem cell transplantation can improve the survival and prognosis(HR=0.05,95%CI 0.01-0.33,P=0.002;HR=0.04,95%CI 0.01-0.36,P=0.004;HR=0.01,95%CI 0.00-0.17,P=0.001;respectively).Conclusions DLBCL of the CNS is aggressive tumor with poor prognosis,the clinical manifestations are complex and diverse,and the diagnosis is challenging.MYD88 L265P is a common and specific gene mutation in primary CNS lymphoma(PCNSL),which is of great significance in the diagnosis a

关 键 词：中枢神经系统肿瘤 淋巴瘤 大B细胞 弥漫性 病理学 临床 突变 MYD88基因 

分 类 号：R739.4[医药卫生—肿瘤]