恶性胃肠道神经外胚层肿瘤3例临床病理学分析

Malignant gastrointestinal neuroectodermal tumor:a clinicopathological analysis of three cases

目的探讨恶性胃肠道神经外胚层肿瘤(gastrointestinal neuroectodermal tumors,GNET)的临床、组织学、超微结构、免疫表型和分子特征、诊断和鉴别诊断。方法收集2013—2022年间空军军医大学西京医院诊断为恶性GNET病例3例。对手术切除标本进行组织学、超微结构观察,免疫组织化学以及分子遗传学检测,并随访患者。结果患者中男性2例,女性1例,肿瘤分别发生于回肠、降结肠和直肠。肿瘤最大径2~4 cm,包膜不完整,切面实性、灰白质韧。镜下大多数瘤细胞呈短梭形或卵圆形,局部上皮样,具有弱嗜酸性或透明胞质,呈实性片状或巢状分布,或假腺泡状排列。电镜观察显示神经内分泌分化,未见黑色素小体。免疫组织化学染色,瘤细胞呈S-100蛋白、SOX10、CD56、突触素和波形蛋白弥漫阳性,而黑色素标志物HMB45和Melan A均阴性。荧光原位杂交检测,3例均显示EWSR1基因重排。1例进行二代基因测序,检测到EWSR1-ATF1基因融合。患者分别随访6个月、3年及5年,复查均提示肺或肝转移,其中1例死亡。结论恶性GNET是一种罕见的胃肠道恶性间叶组织肿瘤,具有独特的组织形态、免疫表型和分子遗传学特征,需与具有类似形态和免疫表型的胃肠道肿瘤鉴别,尤其是透明细胞肉瘤及黑色素瘤等。

Objective To investigate the clinicopathological characteristics of malignant gastrointestinal neuroectodermal tumors(GNET),and to describe their clinical,histological,immunophenotypic,ultrastructural,and molecular features,diagnosis and differential diagnosis.Methods Three cases of malignant GNET were collected at Xijing Hospital of the Fourth Military Medical University,from 2013 to 2022.All patients underwent surgical resection of the tumor.Histological,immunohistochemical(IHC),ultrastructural and molecular genetic analyses were performed,and the patients were followed up for six months,three years and five years.Results There were two males and one female patients.The tumors were located in the ileum,descending colon,and rectum,respectively.Grossly,the tumors were solid,firm,and poorly circumscribed,measured in size from 2 to 4 cm in greatest dimension,and had a greyish-white cut surface.These tumors were histologically characterized by a sheet-like or nested population of oval to spindled cells or epithelioid cells with weakly eosinophilic or clear cytoplasm,small nucleoli and scattered mitoses.Electron microscopy showed neuroendocrine differentiation,and no evidence of melanogenesis.IHC staining showed that the tumor cells were diffusely positive for S-100 protein,SOX10,CD56,synaptophysin and vimentin.They were negative for melanocytic markers,HMB45 and Melan A.All three cases showed split EWSR1 signals consistent with a chromosomal translocation involving EWSR1.Next-generation sequencing in one case confirmed the presence of EWSR1-ATF1 fusion.These patients were followed up for 6 months,3 years and 5 years,respectively,and all of them developed possible lung or liver metastases,and one of them died of multiple pulmonary metastases.Conclusion Malignant GNET has distinctive morphological,IHC,and molecular genetic features and it should be differentiated from other malignancies of the gastrointestinal tract,especially clear cell sarcoma and melanoma.