NTRK3-C22orf34基因融合的成人梭形细胞肉瘤一例报告

A case report of adult spindle cell sarcoma with NTRK3-C22orf34 gene fusion

报告1例NTRK3-C22orf34基因融合的成人梭形细胞肉瘤。男,35岁,入院7个月前无明显诱因出现右大腿外侧肿胀,不伴活动受限。结合患者病史、影像学结果、组织形态、免疫组化特点及分子表型特点,诊断为NTRK3-C22orf34基因融合的成人梭形细胞肉瘤。接受肿瘤切除手术,未行药物靶向治疗。随访至肿瘤切除后8个月,无瘤生存。近年来,神经酪氨酸激酶受体3(neurotrophic tyrosine kinase receptor 3,NTRK3)基因融合的成人梭形细胞肉瘤数量逐年增加,由于此类肿瘤形态多样且数量较少,多数肿瘤依据HE切片难以确诊。随着高通量测序在软组织肿瘤中的广泛应用,NTRK融合基因的梭形细胞肿瘤的诊断难度降低。本例患者高通量测序显示DNA测序发现明确或潜在临床意义变异有NTRK3-C22orf34(突变丰度5%)基因融合合并BRCA1(突变丰度15%)重排,CDKN2A、TP53基因缺失。对NTRK融合基因的梭形细胞肿瘤,特别是肉瘤的形态谱系至今仍然在不断更新。NTRK融合基因梭形细胞肿瘤的治疗以手术切除为主,联合原肌球蛋白受体激酶(tropomyosin receptor kinase,TRK)抑制剂治疗。继发性或获得性耐药性的出现主要与激酶结构域相关的点突变有关,突变可能会降低TRK抑制剂的疗效。

A case of adult spindle cell sarcoma with NTRK3-C22orf34 gene fusion is reported.The patient,a 35-year-old-male,developed lateral swelling of the right thigh without obvious inducement 7 months before admission and was not accompa-nied by limited movement.The patient was diagnosed with adult spindle cell sarcoma with NTRK3-C22orf34 gene fusion based on the medical history,imaging findings,histomorphology,immunohistochemistry and molecular phenotype.The patients underwent tumor resection without drug-targeted therapy and followed up for 8 months after tumor resection and survived without tumor.In recent years,the number of adult spindle cell sarcomas with neurotrophic tyrosine kinase receptor 3(NTRK3)gene fusions have been increasing year by year,and most of them are difficult to diagnose based on HE sections due to the varied morphology and small number of these tumors.With the wide application of high-throughput sequencing in soft tissue tumors,the difficulty of diagnosis of spindle cell tumors with the NTRK fusion gene has decreased.High-throughput sequencing of the patient showed that NTRK3-C22orf34(mutation abundance 5%)gene fusion combined with BRCA1(mutation abundance 15%)rearrangement and deletion of CDKN2A and TP53 genes were found to be of definite or potential clinical significance.The morphologic spectrum of NTRK fusion spindle cell tumors,especially sarcomas,is still evolving.Treatment of NTRK fusion gene spindle cell tumors is based on surgical resection in combination with tropomyosin receptor kinase(TRK)inhibitors.The emergence of secondary or acquired resistance is primarily associated with point mutations associated with the structural domain of the kinase,and mutations may reduce the efficacy of TRK inhibitors.