Abstract：
With the increasing use of next generation sequencing in soft tissue pathology, particularly in neoplasms not fitting any World Health Organization (WHO) category, the spectrum of EWSR1 fusion-associated soft tissue neoplasms has been expanding significantly. Although recurrent EWSR1::ATF1 fusions were initially limited to a triad of mesenchymal neoplasms including clear cell sarcoma of soft tissue, angiomatoid fibrous histiocytoma and malignant gastrointestinal neuroectodermal tumor (MGNET), this family has been expanding. We herein describe 4 unclassified extra-abdominal soft tissue (n = 3) and bone (n = 1) neoplasms displaying epithelioid and round cell morphology and carrying an EWSR1::ATF1 fusion. Affected were 3 males and 1 female aged 20-56 years. All primary tumors were extra-abdominal and deep-seated (chest wall, mediastinum, deltoid, and parapharyngeal soft tissue). Their size ranged 4.4-7.5 cm (median, 6.2). One patient presented with constitutional symptoms. Surgery with (2) or without (1) neo/adjuvant therapy was the treatment. At last follow-up (8-21 months), 2 patients developed progressive disease (1 recurrence; 1 distant metastasis). The immunophenotype of these tumors is potentially misleading with variable expression of EMA (2 of 3), pankeratin (2 of 4), synaptophysin (2 of 3), MUC4 (1 of 3), and ALK (1 of 3). All tumors were negative for S100 and SOX10. These observations point to the existence of heretofore under-recognized group of epithelioid and round cell neoplasms of soft tissue and bone, driven by EWSR1::ATF1 fusions, but distinct from established EWSR1::ATF1-associated soft tissue entities. Their overall morphology and immunophenotype recapitulate that of the emerging EWSR1/FUS::CREB fusion associated intra-abdominal epithelioid/round cell neoplasms. Our cases point to a potentially aggressive clinical behavior. Recognizing this tumor type is mandatory to delineate any inherent biological and/or therapeutic distinctness from other, better-known sarcomas in the differential diagnosis including sclerosing epithelioid fibrosarcoma.
摘要：
随着下一代测序在软组织病理学中的应用越来越多,特别是在不符合任何世界卫生组织（WHO）类别的肿瘤中，EWSR1融合相关软组织肿瘤的范围已显著扩大。尽管复发性EWSR1::ATF1融合最初仅限于间质肿瘤三联征，包括软组织透明细胞肉瘤，血管瘤样纤维组织细胞瘤和恶性胃肠道神经外胚层肿瘤（MGNET），这个家庭一直在扩大。我们在此描述了4种未分类的腹外软组织（n=3）和骨（n=1）肿瘤，表现出上皮样和圆形细胞形态，并带有EWSR1：：ATF1融合。受影响的是3名男性和1名女性，年龄在20-56岁之间。所有原发性肿瘤均为腹外和深层（胸壁，纵隔,三角肌,和咽旁软组织）。它们的大小范围为4.4-7.5厘米（中位数，6.2).一名患者出现体质症状。有（2）或没有（1）新/辅助治疗的手术是治疗。在最后一次随访（8-21个月），2例患者发展为进行性疾病（1例复发；1例远处转移）。这些肿瘤的免疫表型可能会误导EMA的可变表达（3个中的2个），pankeratin（4个中的2个），突触素（2/3），MUC4（1/3），和ALK（3个中的1个）。所有肿瘤均为S100和SOX10阴性。这些观察结果指出，迄今为止，软组织和骨骼的上皮样和圆形细胞肿瘤的存在，由EWSR1::ATF1融合驱动，但与已建立的EWSR1::ATF1相关软组织实体不同。它们的整体形态和免疫表型概括了新兴的EWSR1/FUS::CREB融合相关的腹内上皮样/圆形细胞肿瘤。我们的案例指出了潜在的攻击性临床行为。认识到这种肿瘤类型是强制性的，以描绘任何固有的生物学和/或治疗上的区别，在鉴别诊断中更广为人知的肉瘤，包括硬化性上皮样纤维肉瘤。
