伴IRF4重排的大B细胞淋巴瘤6例报告并文献复习  

Large B-cell lymphoma with IRF4 rearrangement:six case reports and a literature review

作　　者：于颖 孙琦 李承文 贾玉娇 刘薇 王婷玉 吕瑞 阎禹廷 安刚 邱录贵 邹德慧 易树华 Yu Ying;Sun Qi;Li Chengwen;Jia Yujiao;Liu Wei;Wang Tingyu;Lyu Rui;Yan Yuting;An Gang;Qiu Lugui;Zou Dehui;Yi Shuhua(State Key Laboratory of Experimental Hematology,National Clinical Research Center for Blood Diseases,Haihe Laboratory of Cell Ecosystem,Institute of Hematology&Blood Diseases Hospital,Chinese Academy of Medical Sciences&Peking Union Medical College,Tianjin 300020,China)

机构地区：[1]中国医学科学院血液病医院(中国医学科学院血液学研究所),北京协和医学院,实验血液学国家重点实验室,国家血液系统疾病临床医学研究中心,细胞生态海河实验室,天津300020

出　　处：《中华血液学杂志》2022年第6期475-480,共6页Chinese Journal of Hematology

基　　金：国家自然科学基金(81970187、82170193、81920108006、81900203);中国医学科学院医学与健康科技创新工程(CAMS-2017-I2M-3-018、CAMS-2019-I2M-2-009)。

摘　　要：目的探讨伴1RF4重排的大B细胞淋巴瘤的临床、病理学、遗传学特征.方法收集中国医学科学院血液病医院淋巴瘤诊疗中心2017年12月至2021年10月收治的6例伴1RF4重排的大B细胞淋巴瘤患者的临床资料,包括病理学、荧光原位杂交、二代基因测序检测,并复习相关文献.结果①6例患者中男3例,女3例,中位发病年龄33岁.6例患者中3例起病部位为扁桃体,2例为淋巴结,1例为背部肿物.6例患者均采取了RCDOP(利妥昔单抗、环磷酰胺、脂质体阿霉素、长春新碱、泼尼松)方案治疗,随访至2021年11月,6例患者全部存活.②形态学:5例为弥漫性生长,1例为滤泡性生长,瘤细胞体积均为中等至大,病灶多呈膨胀性生长,5例核分裂象易见,6例均未见"星空现象".③免疫组化:4例为生发中心B细胞(GCB)型,2例为non-GCB型;6例均为CD20、PAX5、MUM1、BCL6阳性,CD5阴性;4例CD10阴性;3例BCL2阳性,2例c-MYC阳性.④荧光原位杂交:6例患者IRF4分离探针检测均呈阳性;5例进行BCL6基因重排检测,2例重排阳性;各有5例进行了BCL2、MYC基因重排检测,均为阴性.⑤二代测序:3例患者应用石蜡组织标本进行了二代测序,可见IRF4、TP53、IGLL5、MYD88等淋巴瘤相关基因突变.结论伴IRF4重排的大B细胞淋巴瘤是一种具有独特临床、病理学、遗传学特征的罕见的大B细胞淋巴瘤.对该类型淋巴瘤的发病机制、治疗选择、长期预后仍需进一步探索.Objective To study the clinical,histopathological,and genetic features of large B-cell lymphoma(LBCL)with IRF4 rearrangement.Methods Six patients presenting at our center between December 2017 and October 2021 were evaluated by pathological examination,fluorescence in situ hybridization,and next-generation sequencing.The relevant literature was reviewed.Results①The study sample included three males and three females with a median age of 33 years.Three tumors were in the tonsils,two in the lymphoid nodes,and one in the dorsal lump.All patients were treated using the RCDOP(rituximab,cyclophosphamide,liposomal doxorubicin,vincristine,prednisone)regimen.All of them were alive at the time of follow-up in November 2021.②Microscopic examination showed an entirely follicular pattern in one case and an entirely diffused pattern in 5 cases.The tumor cells were medium to large,and most of the lesions were dilatative with brisk mitotic activity(n=five cases)and no starry sky pattern(n=6 cases).③Four cases exhibited a GCB phenotype,and the other two exhibited a non-GCB phenotype.All of the cases were positive for CD20,PAX-5,MUM,and BCL6,and negative for CD5.Moreover,CD10,BCL2,and c-MYC were positive in 4,3,and 2 cases,respectively.④IRF4 gene rearrangement was identified in all cases,BCL6 gene rearrangement was detected in 5 cases,and 2 cases were positive.BCL2 and MYC gene rearrangement were performed in 5 cases,all negative.⑤Three paraffin tissue samples were used for next-generation sequencing,and lymphoma-related gene mutations such as IRF4,TP53,IGLL5,and MYD88 were detected in 3 cases.Conclusions LBCL with IRF4 rearrangement is a rare entity with unique clinical,pathological,and genetic characteristics.This entity’s pathogenesis,treatment options,and long-term prognosis still need to be explored further.

关 键 词：B细胞淋巴瘤 基因 IRF4 病理学 荧光原位杂交 二代基因测序 

分 类 号：R733.1[医药卫生—肿瘤]