恶性肠胃神经外胚层肿瘤（MGNET），又称“肠胃清细胞肉瘤样肿瘤”，是一种非常罕见、侵袭性的肉瘤，其特征是在肠道内出现，有独特的病理特征和EWSR1/FUS::ATF1/CREB1融合基因。尽管基因相同，但MGNET的临床病理特征与软组织清细胞肉瘤（CCS）差异很大。非肠道性MGNET（E-MGNET）仅有少量病例报道。我们报道了一个11例E-MGNET的系列，是迄今为止最大的报道。检索到在非肠道部位发生的被诊断为MGNET的病例，并获得了临床随访。肿瘤发生在3男8女（年龄为14-70岁，中位数为33岁）的项部（3例）、肩部（1例）、臀部（2例）、眼眶（1例）和舌/喉旁间隙（1例）、膀胱（1例）和肝/副肝韧带（1例）组织上。肿瘤表现为enteric MGNET的形态特征（小，相对均匀，圆形到卵圆形，有圆形、规则的核，包含小的核仁，以多结节和模糊的小叶状生长方式生长，具有固体、伪泡状和伪乳头状结构）。免疫组织化学结果为：S100蛋白（11/11）、SOX10（11/11）、突触素（3/10）、CD56（7/9）、CD117（3/9）、DOG1（0/4）、ALK（4/8）、嗜铬粒蛋白A（0/10）、HMB45（0/11）、Melan-A（0/11）、酪氨酸酶（0/4）和MiTF（0/11）。下一代测序结果为：EWSR1::ATF1（7例）、EWSR1::CREB1（3例）和EWSR1::PBX1（1例）。EWSR1::PBX1阳性的肿瘤与其他病例相似，包括骨吸收样巨细胞，并且阴性表达肌上皮标记物。临床随访（范围：10-70个月；中位数34个月）显示有4例患者死于疾病（确诊后10.5、12、25和64个月），1例患者存活并有广泛转移（确诊后43个月），1例患者仍存活并患有局部残留病变（确诊后11个月），其他4例患者存活无疾病（确诊后10、47、53和70个月）。一例病例太近以至于无法进行随访。罕见的E-MGNET的病理和分子遗传学特征与肠道部位发生的MGNET基本相同。除此之外，典型的E-MGNET可能携带EWSR1::PBX1，这在此类肿瘤中此前没有报道。与肠内位置相同，E-MGNET的行为是侵袭性的，其中至少有50%的患者会发生转移和/或死于疾病。应该将E-MGNET与CCS和其他具有类似融合基因的肿瘤区别开来。ALK表达似乎是携带EWSR1/FUS::ATF1/CREB1融合基因的肿瘤的普遍特征，但不太可能预测ALK抑制剂治疗的疗效。对这种不寻常的肿瘤的理解未来的进展将有望带来改进的命名。Copyright © 2023. Elsevier Inc. 发布。

Malignant gastrointestinal neuroectodermal tumors (MGNET), also known as "gastrointestinal clear cell sarcoma-like tumor", are very rare, aggressive sarcomas characterized by enteric location, distinctive pathologic features, and EWSR1/FUS::ATF1/CREB1 fusions. Despite identical genetics, the clinicopathologic features of MGNET are otherwise quite different from clear cell sarcoma of soft parts (CCS). Only exceptional extra-enteric MGNET (E-MGNET) have been reported. We report a series of 11 E-MGNET, the largest to date. Cases diagnosed as MGNET and occurring in non-intestinal locations were retrieved. Clinical follow-up was obtained. The tumors occurred in 3 males and 8 females (14-70 years of age, median 33 years) and involved the soft tissues of the neck (3), shoulder (1), buttock (2), orbit (1), and tongue/parapharyngeal space (1), the urinary bladder (1) and the falciform ligament/liver (1). Tumors showed morphologic features of enteric MGNET (small, relatively uniform, round to ovoid cells with round, regular nuclei containing small nucleoli, growing in multinodular and vaguely lobular patterns, with solid, pseudoalveolar and pseudopapillary architecture). Immunohistochemical results were: S100 protein (11/11), SOX10 (11/11), synaptophysin (3/10), CD56 (7/9), CD117 (3/9), DOG1 (0/4), ALK (4/8), chromogranin A (0/10), HMB45 (0/11), Melan-A (0/11), tyrosinase (0/4), MiTF (0/11). NGS results were: EWSR1::ATF1 (7 cases), EWSR1::CREB1 (3 cases) and EWSR1::PBX1 (1 case). The EWSR1::PBX1-positive tumor was similar to other cases, including osteoclast-like giant cells, and negative for myoepithelial markers. Clinical follow-up (range: 10 to 70 months; median 34 months) showed 4 patients dead of disease (10.5, 12, 25 and 64 months after diagnosis), 1 patient alive with extensive metastases (43 months after diagnosis), 1 patient alive with persistent local disease (11 months after diagnosis), and 4 alive without disease (10, 47, 53 and 70 months after diagnosis). One case is too recent for follow-up. The clinicopathologic and molecular genetic features of rare E-MGNET are essentially identical to those occurring in intestinal locations. Otherwise-typical E-MGNET may harbor EWSR1::PBX1, a finding previously unreported in this tumor type. As in enteric locations, the behavior of E-MGNET is aggressive, with metastases and/or death from disease in at least 50% of patients. E-MGNET should be distinguished from CCS and other tumors with similar fusions. ALK expression appears to be a common feature of tumors harboring EWSR1/FUS::ATF1/CREB1 fusion but is unlikely to predict therapeutic response to ALK inhibition. Future advances in our understanding of these unusual tumors will hopefully lead to improved nomenclature.Copyright © 2023. Published by Elsevier Inc.