T-bet^(+)记忆B细胞来源边缘区淋巴瘤67例临床病理特征及预后分析  

Clinicopathological features and prognostic analysis of 67 cases of marginal zone lymphoma derived from T-bet positive memory B cell

作　　者：高传书 许周毅 梁家毅 张亮[1] 邵龙飞 王伟[1] 王哲[1,2] Gao Chuanshu;Xu Zhouyi;Liang Jiayi;Zhang Liang;Shao Longfei;Wang Wei;Wang Zhe(Department of Pathology,the First Affiliated Hospital of University of Science and Technology of China/Anhui Provincial Hospital,Hefei 230036,China;Department of Pathology,Xijing Hospital,Air Force Medical University,Xi’an 710032,China)

机构地区：[1]中国科学技术大学附属第一医院(安徽省立医院)病理科,合肥230036 [2]空军军医大学西京医院病理科,西安710032

出　　处：《临床与实验病理学杂志》2025年第2期179-185,190,共8页Chinese Journal of Clinical and Experimental Pathology

基　　金：安徽省高等学校科研项目(2023AH053402)。

摘　　要：目的探讨T-bet^(+)记忆B细胞来源边缘区淋巴瘤(marginal zone lymphoma,MZL)的临床病理学特征及潜在的临床价值。方法收集67例MZL的临床资料,采用HE染色、免疫组化SP法、多重免疫荧光染色和B细胞受体高通量测序技术,观察MZL的组织学、免疫表型和免疫球蛋白重链可变基因(immunoglobulin heavy chain variable gene,IGHV)谱系特征。结果67例MZL中T-bet阳性率为50.75%(34/67),其表达与患者性别、临床分期、Ki67增殖指数等临床病理特征相关(P<0.05),无进展生存较差(P=0.0122)。T-bet是影响MZL疾病进展的风险因素。T-bet^(+)MZL组织镜下常见被T-bet^(+)肿瘤B细胞围绕生长的淋巴滤泡生发中心、腺体滤泡上皮细胞包围T-bet^(+)肿瘤B细胞形成“MALT ball”型淋巴上皮病变及IgG+浆细胞分化的肿瘤细胞。这些组织学特征在T-bet-MZL组织中少见(P<0.05)。T-bet^(+)MZL和T-bet-MZL的VH基因取用存在重叠,常见VH家族为IGHV4和IGHV3,取用片段为IGHV4-34和IGHV3-30。T-bet表达对VH基因的取用未产生偏倚影响(P>0.05)。T-bet表达与MZL的体细胞超突变(somatic hypermutation,SHM)状态有关(P=0.0149),T-bet^(+)MZL的SHM率主要为2%~4.9%,T-bet-MZL的SHM率多数>5%。VH基因取用与患者临床病理特征无关(P>0.05)。T-bet^(+)MZL中IGHV4患者的无进展生存较差(P=0.0382)。结论T-bet在MZL中表达,与MZL的组织学特征、浆细胞免疫表型和IGHV基因SHM等临床病理特征密切相关,患者预后较差,其可能是影响MZL进展的潜在分子学标志物。Purpose To explore the clinicopathological features and potential clinical value of marginal zone lymphoma(MZL)derived from T-bet positive memory B cell.Methods Clinical data of 67 cases of MZL were collected.Hematoxylin-eosin,immunohistochemistry,and multiple immunofluorescence stains,B cell receptor high throughput sequencing technology were used to study the histology,immunophenotype,and immunoglobulin heavy chain variable gene(IGHV)repertoire.Results T-bet was expressed in some MZL patients(34/67,50.75%),which was correlated with clinicopathological characteristics such as gender,clinical stage,and Ki67 proliferation index(P<0.05),and also the progression-free survival was poor(P=0.0122).T-bet positivity was a risk factor affecting the progression of MZL.Microscopically,T-bet positive MZL frequently presented T-bet positive tumor B cells surrounded follicular germinal center,“MALT ball”-type lymphoepithelial lesions,and IgG positive neoplastic plasma cells(P<0.05).T-bet had no biased influence on the VH gene usage(P>0.05).The common VH families were IGHV4 and IGHV3,and the segments were IGHV4-34 and IGHV3-30.The positivity of T-bet was associated with somatic hypermutation(SHM)state(P=0.0149).The SHM was mainly in the range of 2%-4.9%in T-bet positive MZL,while in T-bet negative MZL the SHM was mostly greater than 5%.The VH gene usage was not correlated with the clinicopathological features of patients(P>0.05).IGHV4 was correlated with progression-free survival in T-bet positive MZL(P=0.0382).Conclusion The expression of T-bet in MZL is closely related to the clinicopathological features such as histology,plasma cell immunophenotype and IGHV gene repertoire,and the prognosis of patients is poor,which may be a potential molecular marker affecting the progression of MZL.

关 键 词：淋巴瘤 T-bet^(+)记忆B细胞 边缘区 浆细胞分化 免疫球蛋白重链可变基因 体细胞超突变 

分 类 号：R733.4[医药卫生—肿瘤]