摘要目的 探讨恶性胃肠道神经外胚层肿瘤的临床病理和分子特征,诊断和鉴别诊断要点并分析其生物学行为.方法 收集2例恶性胃肠道神经外胚层肿瘤,观察其临床及影像学特点,组织形态学、免疫表型、分子遗传学特征以及预后,并结合相关文献进行总结和复习.结果 例1男, 57岁.临床表现为反复腹痛伴黑便,影像学检查示盆腔部分小肠肠壁增厚,考虑为淋巴瘤;例2男, 24岁.小肠恶性肿瘤术后1年复发,影像学检查示腹腔和盆腔多发肿块,考虑恶性胃肠道间质肿瘤伴转移.大体检查2例肿瘤主体均位于小肠肌壁间,例1肿瘤直径5.5 cm,例2肿瘤双发,直径分别为4和6 cm.镜下观察:2例肿瘤均由实性排列的小蓝圆和短梭形细胞构成,灶状可见透明细胞;例1散在可见菊形团和假乳头状结构,例2内夹杂大小不等的出血性囊腔.瘤细胞胞质稀少,核仁细小,核分裂象活跃.间质内均可见散在破骨样巨细胞沉积.免疫组织化学染色,2例均弥漫强表达SOX10和S-100蛋白,弥漫或局灶表达神经内分泌标志物(CD56或突触素),例2局灶表达细胞角蛋白;均不表达胃肠道间质肿瘤标志物、肌源性标志物、黑色素标志物(HMB45或Melan A)、树突状细胞标志物以及尤文肉瘤标志物.荧光原位杂交分析2例均存在EWSR1基因重排,二代基因测序分析证实例2存在EWSR1-ATF1基因融合.例1随访16个月未见肿瘤复发和转移,例2术后行多药物联合化疗以及靶向治疗,随访19个月内疾病偶尔稳定但多次复发和转移.结论 恶性胃肠道神经外胚层肿瘤是一种罕见的侵袭性软组织肉瘤,好发于小肠,具有独特的形态学、免疫表型以及分子遗传学特征,需要与多种胃肠道的小蓝圆细胞和梭形细胞肿瘤进行鉴别,仔细的形态学观察并适当地应用免疫组织化学和分子遗传学手段可将其准确的鉴别开来.

abstractsObjective To investigate the clinicopathologic and molecular characteristics, diagnostic, differential diagnostic and prognostic features of malignant gastrointestinal neuroectodermal tumor.Methods Two cases of malignant gastrointestinal neuroectodermal tumor were retrieved;the clinical and radiologic features,histomorphology,immunophenotype,molecular genetics and prognosis were analyzed and the relevant literature reviewed. Results Case 1 was a 57-year-old male, presented with recurrent abdominal pain and melena. Pelvic imaging showed a circumscribed thickening of the wall of a small intestinal segment,and a malignant lymphoma was favored. Case 2 was a 24-year-old male, presented with recurrent small intestinal malignancy. Imaging demonstrated multiple masses in the peritoneal and pelvic cavities,and a malignant gastrointestinal stromal tumor with multiple metastases was suspected. Grossly both tumors were located mainly in the muscularis propria of small intestine. Case 1 showed a single 5.5 cm tumor;and case 2 consisted of two tumors measuring 4 cm and 6 cm respectively. Microscopic examination of both tumors showed small round blue,but focally spindled or clear tumor cells in solid pattern. The tumor cells had scanty cytoplasm, indistinctive nucleoli and brisk mitoses. Osteoclast-like giant cells were dispersed within the stroma. In case 1 rosette-like and pseudo-papillary growth patterns were noted, and in case 2 there were variable-sized hemorrhagic cysts. By immunohistochemistry, both tumors showed strong and diffuse expression of SOX10 and S-100, and focal to diffuse expression of neuroendocrine markers (CD56 or synaptophysin). Case 2 exhibited focal reactivity to pan-cytokeratin. Both tumors lacked expression of markers associated with gastrointestinal stromal tumor, smooth muscle tumor, melanoma (HMB45 or Melan A),dendritic cell tumor and Ewing sarcoma. Fluorescence in situ hybridization analysis demonstrated EWSR1 rearrangement in both tumors and the next generation sequencing confirmed EWSR1-ATF1 gene fusion in case 2. At follow-up of 16 months, case 1 was recurrence or metastasis free; whereas case 2 showed multiple recurrences and metastases within 19 months although stable disease was transiently achieved when treated with combinations of multidrug and targeted chemotherapy. Conclusions Malignant gastrointestinal neuroectodermal tumor is a rare and aggressive soft tissue sarcoma with a predilection for small intestine. It has distinctive morphologic,immunohistochemical and molecular characteristics and needs to be distinguished from other small blue round and spindle cell tumors that occur in the gut. Careful attentions to its characteristic histomorphology with the judicious use of immunohistochemistry and molecular genetics can help to distinguish this tumor from its many mimickers.