同时发生myc和bcl-2/IgH或bcl-6易位的B细胞淋巴瘤临床病理特征

摘要

Objective To identify and investigate clinicopathological features of B cell lymphomas with concurrent myc and bcl-2/IgH or bcl-6 translocations (" double-hit" lymphoma).Methods Tissue microarray was constructed from formalin-fixed and paraffin-embedded tissue samples of aggressive B cell lymphomas diagnosed between 2009 and 2012,including 129 cases of diffuse large B cell lymphoma (DLBCL),5 cases of B-cell lymphoma,unclassifiable with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma (BCLU),7 cases of Burkitt lymphoma and 4 cases of high-grade follicular lymphoma with diffuse large B cell lymphoma component.Interphase fluorescence in-situ hybridization (FISH) was performed with a panel of probes including myc,bcl-2/IgH and bcl-6 to document related gene translocation and copy number changes.Medical record review was performed and follow-up data was recorded.Results Among 145 cases,5 cases (3.4％) of B cell lymphomas with concurrent myc and bcl-2/IgH or bcl-6 rearrangements (double-hit lymphomas) were identified,including 2 cases involving myc and bcl-2 translocations (1 DLBCL and 1 BCLU),and 3 cases involving myc and bcl-6 translocations (all DLBCLs).Three cases with concurrent bcl-2/IgH and bcl-6 translocations were found.Single gene translocations or increase of copy numbers were found in 66 cases,representing 51.2％ (66/129) of all de novo DLBCLs.Ki-67 index of the 5 "double-hit" lymphomas ranged from 60％ to 100％.Clinical follow-up data were available in 4 of the 5 "double-hit" lymphoma patients,three of whom died within 2 years and 1 patient was alive after 36 months of follow-up.Conclusions "Double-hit" B-cell lymphomas are rare and can only be identified by molecular detection.They should not be considered synonymous with BCLU morphologically,and may present entities within other morphological spectra.Most of the patients have a poor prognosis.Further in-depth studies of larger case numbers are required to determine the pathologic and genetic variables of the lesion.%目的 观察同时发生myc和bcl-2/IgH或bcl-6易位的B细胞淋巴瘤(“双击”淋巴瘤)的临床病理学特点.方法 收集145例经活检诊断的侵袭性成熟B细胞淋巴瘤病例石蜡包埋组织,其中包括弥漫性大B细胞淋巴瘤(DLBCL) 129例,具有介于DLBCL和伯基特淋巴瘤(BL)之间特征无法分类的B细胞淋巴瘤(BCLU)5例,BL 7例和高级别滤泡淋巴瘤合并DLBCL4例,在组织芯片上进行myc、bcl-2/IgH和bcl-6系列探针的间期荧光原位杂交检测,记录基因易位情况、拷贝数变化和其他基因异常,同时收集病例的临床、病理学及随访资料.结果 共检测出同时发生myc和bcl-2或bcl-6基因易位(“双击”淋巴瘤)病例5例,检出率5/145(3.4％)；其中myc伴bcl-2易位2例(原形态学诊断1例是DLBCL,1例是BCLU)；myc伴bcl-6易位3例,均为DLBCL.Ki-67阳性指数60％ ～100％.另发现3例bcl-2伴bcl-6易位,均为DLBCL.其余DLBCL病例中出现单个基因易位或拷贝数增加的占51.2％ (66/129).随访资料显示,5例“双击”淋巴瘤患者中3例在诊断后2年内死亡,1例失访,1例随访36个月无病生存.结论 “双击”淋巴瘤属于罕见病例,主要根据基因检测手段来诊断,形态学上不完全等同于2008 WHO分类中的BCLU这一亚型,还可表现为其他的形态学谱系.大部分患者预后差.