Department of Pathology, Indiana University School of Medicine, Indianapolis, Indiana.
Department of Orthopaedic Surgery, The Johns Hopkins Hospital, Baltimore, Maryland.
Mod Pathol. 2024 Sep;37(9):100555. doi: 10.1016/j.modpat.2024.100555. Epub 2024 Jul 6.
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.
未分化圆形细胞肉瘤 (URCS) 是一组具有异质性的肿瘤，包括传统的尤因肉瘤、具有 EWSR1/FUS-非 ETS 融合的圆形细胞肉瘤、CIC 重排肉瘤和具有 BCOR 改变的肉瘤。自 2018 年以来，文献中已经报道了 3 例具有新型 CRTC1::SS18 基因融合的 URCS。在此，我们报告了另外 3 例 CRTC1::SS18 肉瘤病例，使描述的病例数量增加了一倍，并扩展了这种罕见的易位性肉瘤的临床病理特征。与之前报道的病例一起，我们表明男性与女性的比例为 1:2，中位年龄为 34 岁（范围为 12-42 岁）。肿瘤主要发生在下肢的肌内部位。组织学上，所有肿瘤均由均匀的圆形至上皮样细胞组成，细胞具有中等量嗜酸性细胞质，呈片状和巢状生长，伴有突出的促结缔组织增生性基质，类似于促结缔组织增生性小圆细胞肿瘤。免疫组织化学结果是非特异性的，显示 CD99（斑驳）、ALK、GATA3 和 cyclin D1 的表达可变。RNA 测序显示所有病例均存在 CRTC1::SS18 基因融合，涉及染色体 19 上 CRTC1 的外显子 1 至 2（5' 伙伴基因）和染色体 18 上 SS18 的外显子 2 或外显子 4（3' 伙伴基因）。临床病程各不相同。虽然之前有 1 例报告的病例表现出侵袭性行为，导致死亡结局，但另外 2 例的病程相对惰性，在切除前 6 至 7 年逐渐生长。2 例发生转移疾病，包括 1 例双侧肺转移和 1 例局部淋巴结扩散。通过分析临床病理特征，我们旨在提高对这种罕见易位性肉瘤的认识，以更好地了解其生物学潜能，优化患者管理，并扩展 URCS 的当前分类。
