Abstract：
Undifferentiated round cell sarcomas (URCS) represent a diverse group of tumors, including conventional Ewing sarcoma, round cell sarcoma with EWSR1/FUS-non-ETS fusions, CIC-rearranged sarcoma, and sarcoma with BCOR alterations. Since 2018, 3 cases of URCS with a novel CRTC1::SS18 gene fusion have been reported in the literature. Herein, we report 3 additional cases of CRTC1::SS18 sarcoma, thereby doubling the number of described cases and expanding the clinicopathologic features of this rare translocation sarcoma. Together with the previously reported cases, we show that the male-to-female ratio is 1:2 with a median age of 34 years (range, 12-42 years). Tumors occurred primarily in intramuscular locations involving the lower extremity. Histologically, all tumors contained uniform round-to-epithelioid cells with a moderate amount of eosinophilic cytoplasm growing in sheets and nests with prominent desmoplastic stroma reminiscent of desmoplastic small round cell tumor. Immunohistochemical results were nonspecific, demonstrating variable expression of CD99 (patchy), ALK, GATA3, and cyclin D1. RNA sequencing revealed CRTC1::SS18 gene fusions in all cases, involving exons 1 to 2 of CRTC1 (the 5\' partner gene) on chromosome 19 and either exon 2 or exon 4 of SS18 (the 3\' partner gene) on chromosome 18. The clinical course was variable. Although 1 previously reported case demonstrated aggressive behavior with a fatal outcome, 2 others had a relatively indolent course with gradual growth for 6 to 7 years prior to resection. Two cases developed metastatic disease, including 1 case with bilateral lung metastasis and 1 with locoregional spread to a lymph node. By analyzing the clinicopathologic features, we aimed to improve recognition of this rare translocation sarcoma to better understand its biologic potential, optimize patient management, and expand the current classification of URCS.
摘要：
未分化圆形细胞肉瘤（URCS）代表了一组不同的肿瘤，包括传统的尤因肉瘤,EWSR1/FUS-非ETS融合的圆形细胞肉瘤，CIC-重排肉瘤,和带BCOR改变的肉瘤。自2018年以来，文献报道了三例具有新型CRTC1::SS18基因融合的URCS。在这里，我们报告了另外3例CRTC1：：SS18肉瘤，从而使描述的病例数增加了一倍，并扩大了这种罕见易位肉瘤的临床病理特征。加上先前报告的病例，我们显示男女比例为1:2,中位年龄为34岁(范围:12~42岁).肿瘤主要发生在累及下肢的肌内部位。组织学上,所有肿瘤均包含均匀的圆形至上皮样细胞，中等数量的嗜酸性细胞浆生长在片状和巢状中，并具有明显的纤维增生性基质，使人联想到纤维增生性小圆细胞肿瘤（DSRCT）。免疫组织化学结果是非特异性的，显示CD99的可变表达（斑片状），ALK,GATA3和细胞周期蛋白D1。RNA测序显示所有病例中的CRTC1::SS18基因融合,涉及19号染色体上CRTC1(5'伴侣基因)的外显子1-2和18号染色体上SS18(3'伴侣基因)的外显子2或外显子4。临床过程是可变的。虽然先前报道的一例病例表现出具有致命后果的攻击行为，另外两名患者在切除前6-7年有相对缓慢的病程逐渐增长.两例出现转移性疾病,包括1例双侧肺转移和1例局部扩散到淋巴结。通过分析临床病理特征，我们的目标是提高对这种罕见易位肉瘤的认识，以更好地了解其生物学潜力，优化患者管理，并扩展当前URCS的分类。
