淋巴结滤泡辅助T细胞淋巴瘤伴霍奇金/Reed-Sternberg样细胞临床病理学特征、鉴别诊断及基因遗传学特征  

Nodal T-follicular helper cell lymphomas with Hodgkin/Reed-Sternberg-like cells:clinicopathological and genetic features and differential diagnosis

作　　者：杨利群 徐钢[2] 王夏 刘莉 唐萍 严莉 罗丹 YANG Li-qun;XU Gang;WANG Xia;LIU Li;TANG Ping;YAN Li;LUO Dan(Huayin Health Hematopathology Comprehensive Diagnostic Southwest Center and Chengdu Huayin Medical Laboratory,Chengdu 611700,China;Department of Pathology,Sichuan Academy of Medical Sciences and Sichuan Provincial People’s Hospital,Chengdu 610072,China;Huayin Health Hematopathology Comprehensive Diagnostic Center/Huayin Pathological Diagnosis Center,Southern Medical University,Guangzhou 510530,China)

机构地区：[1]华银康血液病理综合诊断西南中心·成都华银医学检验所,成都611700 [2]四川省医学科学院·四川省人民医院病理科,成都610072 [3]华银康血液病理综合诊断中心/南方医科大学·华银病理诊断中心,广州510530

出　　处：《诊断病理学杂志》2023年第7期673-677,共5页Chinese Journal of Diagnostic Pathology

摘　　要：目的探讨淋巴结滤泡辅助T细胞淋巴瘤伴霍奇金/Reed-Sternberg(HRS)样细胞的临床病理学特征、鉴别诊断及基因遗传学特征。方法对5例淋巴结滤泡辅助T细胞淋巴瘤(nTFHL)伴HRS样细胞的临床资料、淋巴结活检组织形态学、免疫组化(IHC)、T/B细胞克隆性评估及NGS(二代测序)特征进行分析。结果5例患者,男性4例,年龄分别为65、40、69、75岁;女性1例,年龄57岁。IHC结果示:异型淋巴细胞表达CD3、CD5、PD-1、BCL-6、CD4、CD10,Ki-67阳性率40~70%;HRS样细胞表达CD30、CD20、PAX-5、C-MYC、MUM-1阳性,Ki-67阳性率90%;1例HRS样细胞表达BOB-1,不表达OCT-2;3例HRS样细胞表达CD15、1例HRS样细胞不表达CD15、1例未行CD15染色;EBV原位杂交示:5例HRS样细胞均为阳性。T/B细胞克隆性评估结果:5例TCRG基因检测到单克隆重排,伴或不伴有IGH基因重排。NGS检测结果示:5例均检测到RHOA基因G17V及TET2基因突变。综合淋巴结形态学、IHC、基因重排及NGS结果诊断为nTFHL伴HRS样细胞。结论nTFHL罕见病例可出现HRS样细胞,这些细胞呈现B细胞免疫表型。肿瘤性T细胞经TCR重排研究证实为克隆性。此外,在肿瘤性T细胞中还发现了RHOA和TET2突变。根据文献报道,TET2突变为导致nTFHL发展的第二次打击RHOA突变奠定了基础。若要深入探讨HRS细胞对于nTFHL细胞遗传学的影响,显微切割HRS样细胞进行单细胞测序及基因检测可能更能说明问题。Objective To investigate the clinicopathological features,differential diagnosis and genetic characteristics of nodal T-follicular helper cell lymphomas with Hodgkin/Reed-Sternberg(HRS)-like cells.Methods The clinical data,lymph node biopsy histology,immunohistochemistry,T/B cell receptor clonality assessment and next-generation sequencing(NGS)result of 5 cases of nodal T-follicular helper cell lymphomas(nTFHL)with HRS-like cells were analyzed.Results The 5 patients with nTFHL,including 4 males at 65,40,69,and 75 years of age,and 1 female at 57 years of age.The immunohistochemical staining showed that the heterotypic lymphocytes expressed CD3,CD5,PD-1,BCL-6,CD4,CD10,as well as Ki-67 in the range 40-70%;HRS-like cells were positive for CD30,CD20,PAX-5,CMYC,MUM-1;1 case of HRS-like cells expressed BOB-1,but not OCT-2;3 cases of HRS-like cells expressed CD15;EBV in situ hybridization(EBER)was positive in HRS-like cells in all 5 cases.T/B cell receptor clonality assessment showed that a monoclonal TCRG gene rearrangement in all 5 cases with or without clonal IgH gene rearrangement.NGS result revealed RHOA gene with G17V mutation and TET2 gene mutation in all 5 cases.Conclusion HRS-like cells can be found in cases of nTFHL.These cells typically show a B-cell immunophenotype.The neoplastic T-cells are clonal confirmed by TCR rearrangement study.In addition,RHOA and TET2 mutations are found in the neoplastic T-cells.According to the literature,TET2 mutation set the stage for second hit of RHOA mutation leading to the development of nTFHL.To further explore the impact of HRS cells on nTFHL pathogenesis single-cell sequencing and genetic testing of microdissected HRS-like cells may be more telling.

关 键 词：结内滤泡辅助T细胞淋巴瘤 经典霍奇金淋巴瘤 HRS样细胞 RHOA TET2 IDH2 DNMT3A 

分 类 号：R733.4[医药卫生—肿瘤]