中枢神经系统骨外间叶性软骨肉瘤临床及病理分析

Extraskeletal mesenchymal chondrosarcoma in central nerve system:a clinicopathological analysis

目的探讨中枢神经系统骨外间叶性软骨肉瘤的临床病理学特征、免疫表型、分子遗传学特征。方法对2014—2019年首都医科大学宣武医院收集的4例中枢神经系统骨外间叶性软骨肉瘤,分别进行临床资料分析、HE染色观察、免疫组织化学染色及逆转录-聚合酶链反应(RT-PCR)检测。结果患者年龄在20~35岁之间,3例病灶位于颅内,1例位于椎管内。镜下改变呈双相结构,即未分化的小细胞与透明软骨岛混合存在,另可见血管外皮瘤样结构及钙化、骨化。免疫组织化学结果显示,肿瘤细胞均表达波形蛋白、SOX9,小细胞区域表达CD99、神经元特异性烯醇化酶、NKX3.1,软骨区域表达S-100蛋白;广谱细胞角蛋白、上皮细胞膜抗原和结蛋白等均阴性,Ki-67阳性指数10%~20%。在分子特征方面,有3例扩增出HEY1-NCOA2融合基因产物,均为HEY1基因的第4号外显子和NCOA2基因的第13号外显子融合。2例术后获得随访信息,分别随访8个月及20个月,均未见肿瘤复发或转移证据。结论骨外间叶性软骨肉瘤是中枢神经系统少见的间叶源性肿瘤,具有特殊的形态学和分子遗传学改变。除了SOX9免疫组织化学阳性表达,新近发现NKX3.1也可作为相对特异的标志物,同时RT-PCR能更准确检测出分子学改变。综合考虑病理形态、免疫组织化学及分子遗传学特征对于诊断该类罕见肿瘤具有重要意义。

Objective To investigate the clinicopathological features,immunophenotype,molecular genetics and prognosis of extraskeletal mesenchymal chondrosarcoma in central nerve system(CNS).Methods The clinicopathological findings,immunohistochemistry and genetic analysis of four cases of extraskeletal mesenchymal chondrosarcoma in Xuanwu Hospital between 2014 and 2019 were reviewed and followed up.Results The ages of patients ranged from 20-35 years.Three patients had intracranial lesions and one had intradural tumor.The characteristic histologic features were undifferentiated small cells together with scattered islands of hyaline cartilage.There was hemangiopericytoma-like pattern with calcification and ossification.The tumor cells were positive for VIM and SOX9;and the small cells were positive for CD99,NSE and NKX3.1.The cells in chondroid matrix were positive for S-100.All tumor cells were negative for markers including CKpan,EMA and desmin.At molecular analysis,HEY1-NCOA2 fusion transcripts were identified in three patients.The fusion points were between exon 4 of HEY1 and exon 13 of NCOA2.Follow-up information was obtained in two patients,and both were free from recurrence or metastasis at 8 and 20 months.Conclusions Extraskeletal mesenchymaI chondrosarcoma is a rare CNS disease with poor prognosis.In addition to SOX9,NKX3.1 can be another useful antibody for the differential diagnosis.The combination of pathological characteristics,immunophenotype and genetic profile of tumor is essential for diagnosis.