唾液腺干燥综合征继发黏膜相关淋巴组织淋巴瘤的临床病理分析  

Clinicopathological analysis of mucosa associated lymphoid tissue lymphoma secondary to Sjögren’s syndrome in salivary gland

作　　者：池彦廷 张延平[3] 张秋露 刘翠苓[5,6] 李斌斌[1,2] CHI Yan-ting;ZHANG Yan-ping;ZHANG Qiu-lu;LIU Cui-ling;LI bin-bin(Department of Oral Pathology,Peking University School and Hospital of Stomatology&National Clinical Research Center for Oral Diseases&National Engineering Laboratory for Digital and Material Technology of Stomatology&Beijing Key Laboratory of Digital Stomatology,Beijing 100081,China;Research Unit of Precision Pathologic Diagnosis in Tumors of the Oral and Maxillofacial Regions,Chinese Academy of Medical Sciences(2019RU034),Beijing 100081,China;Department of Pathology,First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,China;West China School of Medicine,Sichuan University,Chengdu 610041,China;Department of Pathology,Peking University School of Basic Medical Science,Beijing 100191,China;Department of Pathology,Peking University Third Hospital,Beijing 100191,China)

机构地区：[1]北京大学口腔医学院·口腔医院,病理科国家口腔疾病临床医学研究中心口腔数字化医疗技术和材料国家工程实验室口腔数字医学北京市重点实验室,北京100081 [2]中国医学科学院口腔颌面部肿瘤精准病理诊断创新单元(2019RU034),北京100081 [3]郑州大学第一附属医院病理科,郑州450052 [4]四川大学华西临床医学院,成都610041 [5]北京大学基础医学院病理学系,北京100191 [6]北京大学第三医院病理科,北京100191

出　　处：《北京大学学报（医学版）》2021年第1期40-45,共6页Journal of Peking University:Health Sciences

基　　金：中国医学科学院医学与健康科技创新工程项目(2019-I2M-5-038);北京市自然科学基金(7102101)。

摘　　要：目的:分析唾液腺干燥综合征(Sjögren’s syndrome,SS)继发黏膜相关淋巴组织(mucosa associated lym-phoid tissue,MALT)淋巴瘤(SS-MALT淋巴瘤)的临床病理特点,并探索联合应用组织病理形态、蛋白表达和分子表型检测在唾液腺SS-MALT淋巴瘤病理诊断和预后评估中的应用价值。方法:在1997年1月至2016年12月就诊于北京大学口腔医院并经病理确诊为唾液腺SS的260例患者中收集到16例SS-MALT淋巴瘤患者,另选取12例无唾液腺SS病史的MALT淋巴瘤(非SS-MALT淋巴瘤)患者作为对照,回顾性分析患者临床资料并随访。同时,应用苏木精-伊红染色、免疫组织化学、聚合酶链式反应(polymerase chain reaction,PCR)和荧光原位杂交技术(fluorescence in situ hybridization,FISH)观察组织病理变化,检测轻链限制性表达、免疫球蛋白(immunoglobulin,Ig)基因重排、染色体易位及基因异常,评价其在病理诊断和预后判断中的作用。结果:SS进展为MALT淋巴瘤的恶变率约为6.15%,恶变时间为3~240个月不等,其中有2例因发生高级别转化而死亡。SS-MALT淋巴瘤镜下表现为腺泡不同程度的萎缩破坏,以中心细胞样细胞为主的淋巴细胞弥漫浸润并破坏上皮岛。SS-MALT淋巴瘤组CD20和Pax5均为阳性(阳性率100%);Ki-67指数≤10%者占50%,>10%者占50%;AE1/AE3染色显示有残存腺上皮(93.75%)。全部病例肿瘤细胞CD3ε均为阴性,CD138染色显示有数量不等的浆细胞。37.5%的SS-MALT淋巴瘤患者检测到κ和λ轻链限制性表达。SS-MALT淋巴瘤组中免疫球蛋白重链(immunoglobulin heavy chain,IgH)-FR1、IgH-FR2、IgH-FR3、免疫球蛋白κ链(immunoglobulin kappa chain,IgK)-A、IgK-B的阳性检出率分别为33.3%、53.3%、33.3%、20.0%、26.7%,联合应用IgH和IgK的阳性检出率达93.3%。MALT1双色分离探针阳性率36.4%,IGH双色分离探针阳性率27.3%,BCL6双色分离探针阳性率27.3%;三种探针共同使用的基因异常检出率为72.7%。结论:唾液腺SS-MObjective:To analyze the clinicopathological characteristics of mucosa associated lymphoid tissue(MALT)lymphoma secondary to Sjögren’s syndrome(SS)(SS-MALT lymphoma)in salivary gland and to explore the value of the combined application of histopathological morphology,protein expression and molecular phenotype in pathological diagnosis and prognostic evaluation of SS-MALT lymphoma.Methods:Sixteen patients with SS-MALT lymphoma were collected from 260 patients who were diagnosed with SS in Peking University School and Hospital of Stomatology from January 1997 to December 2016.Twelve patients with non-MALT lymphoma secondary to SS(non-SS-MALT lymphoma)in salivary gland were selected as controls.The clinical data of the patients were retrospectively reviewed and analyzed.All the patients were followed up until December 20,2019.Hematoxylin-eosin staining,immunohistochemistry,polymerase chain reaction(PCR)and fluorescence in situ hybridization(FISH)techniques were used to observe the histologic characteristics and to detect the manifestations of light chain restrictive expression,immunoglobulin(Ig)gene clonal rearrangement,chromosome translocation and gene abnormality,so as to evaluate their values in pathological diagnosis and prognostic evaluation.Results:The malignant transformation rate of SS to MALT lymphoma was about 6.15%,ranged from 3 to 240 months,during which 2 patients died due to high-level deterioration.Microscopically,the acini of the glandular tissue were atrophied and destroyed.The tumor cells dominated by central cell-like lymphocytes grew diffusely,destroying the epithelial islands.All SS-MALT lymphoma cases were positive in CD20 and Pax5.Half of them had the Ki-67 proliferation index of 10%or less,and half greater than 10%.93.75%cases expressed AE1/AE3 protein,which showed the residual glandular epithelium.All the tumor cells were negative in CD3ε,and the plasma cells were detected by CD138 antigen.The light chain restrictive expression ofκandλwas 37.5%in SS-MALT lymphoma group.The positive det

关 键 词：干燥综合征 黏膜相关淋巴组织淋巴瘤 免疫组织化学 聚合酶链反应 原位杂交 荧光 

分 类 号：R733.41[医药卫生—肿瘤]