血管免疫母细胞性T细胞淋巴瘤临床与分子病理学特征分析  

Analysis of clinicopathological and molecular abnormalities of angioimmunoblastic T-cell lymphoma

作　　者：时云飞[1] 王豪杰 刘卫平[3] 米岚[3] 龙孟平 刘雁飞 赖玉梅[1] 周立新[1] 刁新婷 李向红[1] SHI Yun-fei;WANG Hao-jie;LIU Wei-ping;MI Lan;LONG Meng-ping;LIU Yan-fei;LAI Yu-mei;ZHOU Li-xin;DIAO Xin-ting;LI Xiang-hong(Department of Pathology,Peking University Cancer Hospital&Institute,Beijing 100142,China;Central Laboratory,Peking University Cancer Hospital&Institute,Beijing 100142,China;Department of Lymphoma,Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education),Peking University Cancer Hospital&Institute,Beijing 100142,China)

机构地区：[1]北京大学肿瘤医院暨北京市肿瘤防治研究所病理科,北京100142 [2]北京大学肿瘤医院暨北京市肿瘤防治研究所中心实验室,北京100142 [3]北京大学肿瘤医院暨北京市肿瘤防治研究所淋巴瘤科,恶性肿瘤发病机制及转化研究教育部重点实验室,北京100142

出　　处：《北京大学学报（医学版）》2023年第3期521-529,共9页Journal of Peking University:Health Sciences

摘　　要：目的:分析血管免疫母细胞性T细胞淋巴瘤(angioimmunoblastic T-cell lymphoma,AITL)病理学特征、基因改变及预后的影响因素。方法:选择北京大学肿瘤医院病理科2007年6月至2021年11月明确诊断且有完整随访信息的AITL患者病例资料进行回顾性分析,对病例进行形态学分型[Ⅰ型:淋巴结反应性增生(lymphoid tissue reactive hyperplasia,LRH)样;Ⅱ型:边缘区淋巴瘤(marginal zone lymphoma,MZL)样;Ⅲ型:外周T细胞淋巴瘤非特指型(peripheral T-cell lymphoma,not specified,PTCL-NOS)样]。结合免疫组化染色评估肿瘤有无滤泡辅助T细胞(follicular helper T cell,TFH)表型,生发中心(germinal center,GC)外滤泡树突细胞(follicular dendritic cells,FDC)增生,Hodgkin和Reed-Sternberg(HRS)样细胞及大B(细胞淋巴瘤)转化;计数每个高倍视野(high power field,HPF)Epstein-Barr病毒(Epstein-Barr virus,EBV)阳性细胞含量;按需要完善T细胞受体(T-cell receptor,TCR)/免疫球蛋白(immunoglobulin,IG)基因重排检测和靶向外显子二代测序(targeted exome sequencing,TES)检测。结果:共收集患者61例,形态分型Ⅰ型7例(11.4%)、Ⅱ型31例(50.8%)、Ⅲ型23例(37.8%),51例(83.6%)具有明确TFH表型,有不同程度GC外FDC网架增生(中位20.0%),14例(23.0%)有HRS样细胞,7例(11.5%)有大B转化。42.6%(26/61)的病例属于EBV高含量(>10个/HPF)。TCR/IG重排分析57.9%TCR^(+)/IG^(-)(11/19),26.3%TCR^(+)/IG^(+)(5/19),10.5%TCR^(-)/IG^(-)(2/19),5.3%TCR^(-)/IG^(+)(1/19)。TES检测RHOA突变66.7%(20/30),IDH2突变23.3%(7/30),TET2突变80.0%(24/30),DNMT3A突变33.3%(10/30)。TES检测30例患者分为(1)IDH2和RHOA共突变组(7例):Ⅱ型6例,Ⅲ型1例,具典型TFH表型,未见HRS细胞和大B转化;(2)单RHOA突变组(13例):Ⅰ型1例,Ⅱ型6例,Ⅲ型6例,不具典型TFH表型5例,伴HRS细胞6例,伴大B转化2例,TCR^(-)/IG^(-)1例,TCR^(-)/IG^(+)1例,TCR^(+)/IG^(+)1例;(3)仅TET2和/或DNMT3A突变组(7例):Ⅱ型3例,Ⅲ型4例,均具典型TFH表型,伴HRS细胞2例,伴大B转化Objective:To analyze the clinicopathological features,molecular changes and prognostic factors in angioimmunoblastic T-cell lymphoma(AITL).Methods:Sixty-one cases AITL diagnosed by Department of Pathology of Peking University Cancer Hospital were collected with their clinical data.Morphologically,they were classified as typeⅠ[lymphoid tissue reactive hyperplasia(LRH)like];typeⅡ[marginal zone lymphoma(MZL)like]and typeⅢ[peripheral T-cell lymphoma,not specified(PTCL-NOS)like].Immunohistochemical staining was used to evaluate the presence of follicular helper T-cell(TFH)phenotype,proliferation of extra germinal center(GC)follicular dendritic cells(FDCs),presence of Hodgkin and Reed-Sternberg(HRS)-like cells and large B transformation.The density of Epstein-Barr virus(EBV)+cells was counted with slides stained by Epstein-Barr virus encoded RNA(EBER)in situ hybridization on high power field(HPF).T-cell receptor/immunoglobulin gene(TCR/IG)clonality and targeted exome sequencing(TES)test were performed when necessary.SPSS 22.0 software was used for statistical analysis.Results:Morphological subtype(%):11.4%(7/61)cases were classified as typeⅠ;50.8%(31/61)as typeⅡ;37.8%(23/61)as typeⅢ.83.6%(51/61)cases showed classical TFH immunophenotype.With variable extra-GC FDC meshwork proliferation(median 20.0%);23.0%(14/61)had HRS-like cells;11.5%(7/61)with large B transformation.42.6%(26/61)of cases with high counts of EBV.57.9%(11/19)TCR^(+)/IG^(-),26.3%(5/19)TCR^(+)/IG^(+),10.5%(2/19)were TCR^(-)/IG^(-),and 5.3%(1/19)TCR^(-)/IG^(+).Mutation frequencies by TES were 66.7%(20/30)for RHOA,23.3%(7/30)for IDH2 mutation,80.0%(24/30)for TET2 mutation,and 33.3%(10/30)DNMT3A mutation.Integrated analysis divided into four groups:(1)IDH2 and RHOA co-mutation group(7 cases):6 cases were typeⅡ,1 case was typeⅢ;all with typical TFH phenotype;HRS-like cells and large B transformation were not found;(2)RHOA single mutation group(13 cases):1 case was typeⅠ,6 cases were typeⅡ,6 cases were typeⅢ;5 cases without typical TFH ph

关 键 词：T细胞 淋巴瘤 病理学 基因突变 预后 

分 类 号：R732.2[医药卫生—肿瘤]