儿童NTRK重排间叶源性肿瘤临床病理学观察  

Clinicopathological characteristics of NTRK-rearranged mesenchymal tumors in childhood

作　　者：殷敏智[1] 马靖 何巧 沈萍 陈洁枫 金晓婷 张忠德[1] Chik Hong Kuick Chen Huiyi Eileen Hui Qi Ng Sze Jet Aw Kenneth Tou En Chang Yin Minzhi;Ma Jing;He Qiao;Shen Ping;Chen Jiefeng;Jin Xiaoting;Zhang Zhongde;Chik Hong Kuick;Chen Huiyi;Eileen Hui Qi Ng;Sze Jet Aw;Kenneth Tou En Chang(Department of Pathology,Shanghai Children′s Medical Center,Shanghai Jiaotong University School of Medicine,Shanghai 200127,China;Department of Pathology and Laboratory Medicine,KK Women′s and Children′s Hospital,Singapore 229899,Singapore)

机构地区：[1]上海交通大学医学院附属上海儿童医学中心病理科,200127 [2]Department of Pathology and Laboratory Medicine,KK Women′s and Children′s Hospital,Singapore 229899,Singapore

出　　处：《中华病理学杂志》2020年第7期675-680,共6页Chinese Journal of Pathology

基　　金：上海交通大学转化医学交叉研究基金(ZH2018ZDA25)。

摘　　要：目的:探讨儿童NTRK重排间叶源性肿瘤临床和病理学特征,以提高对该类疾病的认识。方法:收集上海交通大学医学院附属上海儿童医学中心及新加坡KK Women′s and Children′s Hospital从2017年1月至2019年9月5例手术切除标本,采用EnVision法检测免疫组织化学表型,荧光原位杂交(FISH)检测相关基因并对NTRK基因重排进行克隆性分析。结果:该组5例患儿,3例男性,2例女性。年龄从3个月到13岁,部位包括软组织(膝、胸腔、腹壁)和肾,肿瘤大小为4.5~12.5 cm。组织学检查主要呈梭形细胞肿瘤,浸润性生长,可伴有炎性细胞。免疫表型上,肿瘤细胞阳性表达Pan-TRK,分子检测均存在NTRK基因重排,包括DCTN1-NTRK1的发现。除2例目前接受靶向药物治疗,其余均为无疾病进展病例,随访时间9~29个月。结论:NTRK重排间叶源性肿瘤,其肿瘤发生部位广泛,组织学图像多变。免疫组织化学Pan-TRK可以帮助诊断,NTRK基因检测确认其存在重排是诊断的金标准,对不能完整切除或有复发、转移病例建议靶向药物治疗。ObjectiveTo investigate the clinical and pathological features of pediatric NTRK-rearranged tumors.MethodsFour NTRK-rearranged soft tissue tumors and one renal tumor at Shanghai Children′s Medical Center,Shanghai Jiaotong University and Singapore KK Women′s and Children′s Hospital from January 2017 to September 2019 were identified.Pan-TRK immunohistochemistry,and the ALK and ETV6 gene break-apart fluorescence in situ hybridizations(FISH)were performed.NTRK gene rearrangement was detected using sequencing-based methods.ResultsThere were 3 males and 2 females in this study.The patients were between 3 months and 13 years of age.Histologically,the tumors were infiltrative spindle cell tumors with variable accompanying inflammatory cells.Immunohistochemistry showed positive reactivity for pan-TRK in all tumors,with nuclear staining for NTRK3 fusion,and cytoplasmic staining for NTRK1 fusion.The molecular testing revealed NTRK gene fusions(one each of TPM3-NTRK1,ETV6-NTRK3 and DCTN1-NTRK1,and two cases of LMNA-NTRK1).Two patients were receiving larotrectinib.The others were are well without disease,with follow-up durations of 9 to 29 months.ConclusionsNTRK-rearranged mesenchymal tumors from soft tissue sites and kidney are identified.A novel DCTN1-NTRK1 fusion is described.Pan-TRK immunohistochemistry is useful for diagnosis.NTRK-targeted therapy may be an option for unresectable,recurrent or metastatic cases.

关 键 词：儿童 免疫组织化学 分子靶向治疗 间叶源性肿瘤 

分 类 号：R738.6[医药卫生—肿瘤]