甲状腺弥漫性大B细胞淋巴瘤临床病理特征、基因突变谱及预后分析  

Clinicopathologic characteristics,gene mutation profile and prognostic analysis of thyroid diffuse large B-cell lymphoma

作　　者：杜沚珊 王玥 石子旸 施晴 易红梅 董磊[1] 王黎[1] 程澍[1] 许彭鹏[1] 赵维莅[1] DU Zhishan;WANG Yue;SHI Ziyang;SHI Qing;YI Hongmei;DONG Lei;WANG Li;CHENG Shu;XU Pengpeng;ZHAO Weili(Department of Hematology,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,State Key Laboratory of Medical Genomics,Shanghai Institute of Hematology,Shanghai 200025,China)

机构地区：[1]上海交通大学医学院附属瑞金医院血液科,医学基因组学国家重点实验室,上海血液学研究所,上海200025

出　　处：《上海交通大学学报（医学版）》2024年第1期64-71,共8页Journal of Shanghai Jiao tong University:Medical Science

基　　金：国家自然科学基金(82130004,81830007,81670176,82070204);上海交通大学医学院“双百人”项目(20230013)。

摘　　要：目的·探究甲状腺弥漫性大B细胞淋巴瘤(diffuse large B-cell lymphoma,DLBCL)临床病理特征、基因突变谱及预后相关因素。方法·回顾性分析2003年11月—2021年12月上海交通大学医学院附属瑞金医院收治的66例初次诊断为甲状腺DLBCL患者[原发甲状腺DLBCL 23例(34.8%),继发甲状腺DLBCL 43例(65.2%)]的临床病理资料,并进行生存和预后因素分析。其中40例甲状腺DLBCL患者进行了靶向测序(55个淋巴瘤相关基因)以评估基因突变情况。结果·继发甲状腺DLBCL患者Ann Arbor分期Ⅲ~Ⅳ期(P=0.000)、乳酸脱氢酶(lactate dehydrogenase,LDH)升高(P=0.043)、结外器官受累数目≥2个(P=0.000)、非生发中心来源(non-GCB)(P=0.030)、MYC和BCL2蛋白双表达(double expression,DE)(P=0.026)、国际预后指数3~5分(P=0.000)的比例高于原发甲状腺DLBCL患者,其接受甲状腺手术切除的比例(P=0.012)低于原发甲状腺DLBCL患者。原发甲状腺DLBCL患者完全缓解(complete response,CR)率高于继发患者(P=0.039)。55例患者(83%)接受以利妥昔单克隆抗体联合环磷酰胺、阿霉素、长春新碱及泼尼松(R-CHOP)为基础的一线治疗方案,其中原发甲状腺DLBCL患者预期5年无进展生存(progress free survive,PFS)率95.0%,高于继发患者的49.7%(P=0.010)。单因素分析显示:Ann ArborⅢ~Ⅳ期(HR=4.411,95%CI 1.373~14.170)、LDH升高(HR=5.500,95%CI 1.519~19.911)、non-GCB(HR=5.291,95%CI 1.667~16.788)、DE(HR=6.178,95%CI 1.813~21.058)是甲状腺DLBCL患者PFS的不良预后因素;Ann ArborⅢ~Ⅳ期(HR=7.088,95%CI 0.827~60.717)、LDH升高(HR=6.982,95%CI 0.809~60.266)、DE(HR=18.079,95%CI 1.837~177.923)是总生存(overall survival,OS)时间的不良预后因素。多因素分析显示:Ann ArborⅢ~Ⅳ期(HR=4.693,95%CI 1.218~18.081)和LDH升高(HR=5.058,95%CI 1.166~21.941)是甲状腺DLBCL患者PFS的独立不良预后因素。靶向测序结果显示,TET2(n=14,35%)、KMT2D(n=13,32%)、TP53(n=11,28%)、GNA13(n=10,25%)、KMT2C(n=9,22%)突变频率>20%,�Objective·To analyze the clinicopathologic characteristics,gene mutation profile,and prognostic factors of thyroid diffuse large B-cell lymphoma(DLBCL).Methods·From November 2003 to December 2021,a total of 66 patients with thyroid DLBCL[23 cases(34.8%)with primary thyroid DLBCL,and 43 cases(65.2%)with secondary thyroid DLBCL]admitted to Ruijin Hospital,Shanghai Jiao Tong University School of Medicine were retrospectively analyzed for their clinicopathological data,survival and prognostic factors.Gene mutation profiles were evaluated by targeted sequencing(55 lymphoma-related genes)in 40 patients.Results·Compared to primary thyroid DLBCL,secondary thyroid DLBCL had advanced ratio of Ann Arbor stageⅢ‒Ⅳ(P=0.000),elevated serum lactate dehydrogenase(LDH)(P=0.043),number of affected extranodal involvement≥2(P=0.000),nongerminal center B cell(non-GCB)(P=0.030),BCL-2/MYC double expression(DE)(P=0.026),and international prognostic index(IPI)3‒5-scores(P=0.000).The proportion of patients who underwent thyroid surgery(P=0.012)was lower than that of patients with primary thyroid DLBCL.The complete remission(CR)rate in primary thyroid DLBCL patients was higher than that in secondary thyroid DLBCL patients(P=0.039).Fifty-five patients(83%)received rituximab combined with cyclophosphamide,doxorubicin,vincristine,and prednisone(R-CHOP)-based first-line regimen.The estimated 5-year progression free survival(PFS)rate of primary thyroid DLBCL patients was 95.0%,higher than the 49.7%of the secondary patients(P=0.010).Univariate analysis showed that Ann ArborⅢ‒Ⅳ(HR=4.411,95%CI 1.373‒14.170),elevated LDH(HR=5.500,95%CI 1.519‒19.911),non-GCB(HR=5.291,95%CI 1.667‒16.788),and DE(HR=6.178,95%CI 1.813‒21.058)were adverse prognostic factors of PFS in patients with thyroid DLBCL.Ann ArborⅢ‒Ⅳ(HR=7.088,95%CI 0.827‒60.717),elevated LDH(HR=6.982,95%CI 0.809‒60.266),and DE(HR=18.079,95%CI 1.837‒177.923)were adverse prognostic factors of overall survival(OS).Multivariate analysis showed that Ann ArborⅢ‒

关 键 词：甲状腺 弥漫性大B细胞淋巴瘤 临床病理特征 基因突变谱 预后分析 

分 类 号：R733.4[医药卫生—肿瘤]