Zhao M, Zhao T W, Ma J, Wu C Y, Chen L, Ru G Q, He X L
Department of Pathology, Zhejiang Provincial People's Hospital, Hangzhou 310014, China.
Zhonghua Bing Li Xue Za Zhi. 2017 Nov 8;46(11):750-755. doi: 10.3760/cma.j.issn.0529-5807.2017.11.003.
To investigate the clinicopathologic and molecular characteristics, diagnostic, differential diagnostic and prognostic features of malignant gastrointestinal neuroectodermal tumor. 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. 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. 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.
探讨恶性胃肠道神经外胚层肿瘤的临床病理及分子特征、诊断、鉴别诊断和预后特征。检索出2例恶性胃肠道神经外胚层肿瘤病例；分析其临床和影像学特征、组织形态学、免疫表型、分子遗传学及预后，并复习相关文献。病例1为57岁男性，表现为反复腹痛和黑便。盆腔影像学检查显示小肠段肠壁局限性增厚，考虑为恶性淋巴瘤。病例2为24岁男性，表现为复发性小肠恶性肿瘤。影像学检查显示腹膜和盆腔内有多个肿块，怀疑为伴有多发转移的恶性胃肠道间质瘤。大体上，两个肿瘤均主要位于小肠固有肌层。病例1为一个5.5 cm的肿瘤；病例2由两个分别为4 cm和6 cm的肿瘤组成。两个肿瘤的显微镜检查均显示为小圆形蓝色细胞，但局部为梭形或透明细胞，呈实性生长模式。肿瘤细胞胞质稀少，核仁不明显，有活跃的有丝分裂。破骨细胞样巨细胞散在于间质中。病例1可见玫瑰花结样和假乳头样生长模式，病例2有大小不一的出血性囊肿。免疫组化显示，两个肿瘤均有SOX10和S-100的强弥漫性表达，神经内分泌标志物（CD56或突触素）呈局灶性至弥漫性表达。病例2对泛细胞角蛋白有局灶性反应。两个肿瘤均缺乏与胃肠道间质瘤、平滑肌瘤、黑色素瘤（HMB45或Melan A）、树突状细胞瘤和尤因肉瘤相关的标志物表达。荧光原位杂交分析显示两个肿瘤均有EWSR1重排，二代测序证实病例2存在EWSR1-ATF1基因融合。随访16个月时，病例1无复发或转移；而病例2在19个月内出现多次复发和转移，尽管联合多药和靶向化疗曾短暂达到疾病稳定。恶性胃肠道神经外胚层肿瘤是一种罕见且侵袭性强的软组织肉瘤，好发于小肠。它具有独特的形态学、免疫组化和分子特征，需要与肠道中出现的其他小圆形蓝色和梭形细胞肿瘤相鉴别。仔细观察其特征性组织形态学，并合理运用免疫组化和分子遗传学有助于将该肿瘤与其众多的相似肿瘤区分开来。
