荧光原位杂交检测EWSR1基因重排阴性的骨与软组织未分化小圆细胞肉瘤病例再分析  

Reassessment of EWSR1 gene rearrangement-negative undifferentiated round cell sarcomas in bone and soft tissues by fluorescence in situ hybridization

作　　者：李兰[1] 张铭[1] 孙晓淇[1] 刘美 徐海荣[3] 张婷婷[1] 黄啸原[1] 丁宜[1] Li Lan;Zhang Ming;Sun Xiaoqi;Liu Mei;Xu Hairong;Zhang Tingting;Huang Xiaoyuan;Ding Yi(Department of Pathology,Beijing Jishuitan Hospital(the Fourth Medical College of Peking University),Beijing 100035,China;Department of Labratry,Ji′nan People′s Hospital of Shandong Province,Ji′nan 271100,China)

机构地区：[1]北京积水潭医院(北京大学第四临床医学院)病理科,100035 [2]山东省济南市人民医院检验科,271100 [3]北京积水潭医院(北京大学第四临床医学院)骨肿瘤科,100035

出　　处：《中华病理学杂志》2021年第7期745-750,共6页Chinese Journal of Pathology

基　　金：北京市科技计划(Z171100001017134);北京积水潭医院“学科新星”计划(XKXX201811)。

摘　　要：目的筛选EWSR1基因重排阴性的未分化小圆细胞肉瘤中的CIC重排肉瘤(CRS)或BCOR-CCNB3肉瘤(BCS),总结其临床病理特征。方法收集北京积水潭医院病理科2014年1月至2020年9月病理诊断为未分化小圆细胞肉瘤且疑为尤文肉瘤但荧光原位杂交(FISH)未检测到EWSR1基因重排的病例28例,采用FISH检测CIC基因断裂及BCOR基因断裂情况,从中筛选出CRS或BCS,部分BCS经逆转录聚合酶链反应(RT-PCR)验证。结果筛选出CRS 5例,BCS 6例,各占EWSR1基因重排阴性的未分化小圆细胞肉瘤的17.9%(5/28)和21.4%(6/28),两者总占比为39.3%(11/28)。CRS 5例中男性4例,女性1例,年龄15~65岁。其中4例发生于软组织,1例发生于骨组织。肿瘤细胞稍大,泡状核,核仁明显,呈弥漫片状、分叶状或血管周生长,间质可见纤维间隔,部分黏液变。肿瘤细胞不同程度表达CD99,部分病例表达Fli-1、TLE1、DUX4、WT-1、Calretinin。5例CRS患者随访7~22个月,2例死亡,2例无瘤生存,1例失访。BCS 6例中男性5例,女性1例,年龄8~20岁。其中4例发生于骨组织,2例发生于软组织。肿瘤细胞短梭形或卵圆形,核染色质细腻,核仁不明显,排列成实性或束状生长,间质富于毛细血管网,间或有细胞稀疏区伴间质黏液变。肿瘤细胞表达TLE1、CCNB3,少部分病例表达CD99、Fli-1。3例经RT-PCR验证为BCOR-CCNB3基因融合。6例BCS患者随访1~68个月,1例死亡,5例无瘤生存。结论39.3%的EWSR1基因重排阴性的未分化小圆细胞肉瘤为CRS或BCS肉瘤,分子检测有助于其正确诊断。Objective To unravel the CIC rearrangement sarcomas and BCOR-CCNB3 sarcomas from EWSR1 rearrangement-negative undifferentiated round cell sarcomas in the bone and soft tissues.Methods Twenty-eight cases of EWSR1 rearrangement-negative undifferentiated round cell sarcomas of bone and soft tissues,tested for CIC rearrangement and BCOR rearrangement by fluorescence in situ hybridization and related immunostaining were analyzed,and some of the BCOR rearrangement cases were verified by reverse transcription-polymerase chain reaction.Results Five of 28(17.9%)tested cases were positive for CIC rearrangement and six(21.4%)for BCOR rearrangement.Histopathologically,CIC rearrangement sarcomas comprised nodular aggregates of round to polygonal cells,containing hyperchromatic nuclei,prominent nucleoli and moderate cytoplasm,with focal variable necrosis and myxoid stroma.BCOR-CCNB3 sarcomas mostly comprised diffusely arranged,round to oval to short spindly cells with angulated nuclei,vesicular chromatin,inconspicuous nucleoli and interspersed vessels.Immunohistochemically,five of six BCOR-CCNB3 sarcomas showed CCNB3 immunostaining,which could be helpful for diagnosis.Two patients with CIC rearrangement sarcoma died of the diseases in seven months and twenty-two months.One patient with BCOR-CCNB3 sarcoma died of the diseases in forty-six months.Conclusions Overall,39.3%of the EWSR1 rearrangement-negative undifferentiated round cell sarcomas are CIC rearrangement sarcomas and BCOR-CCNB3 sarcomas.Molecular testing is helpful for diagnosis.

关 键 词：肉瘤 骨肿瘤 软组织肿瘤 原位杂交 荧光 基因重排 

分 类 号：R738.1[医药卫生—肿瘤] R738.6[医药卫生—临床医学]