Çetin Sirma, Ünverengil Gökçen, Yilmaz İsmail, Ahmed Melin Aydan, Yildirim Miray Ülkü, Özkan Eriş, Özger Harzem, Bilgiç Bilge
Department of Pathology, Istanbul University, Istanbul Faculty of Medicine.
Department of Pathology, Abdulhamid Han Research and Training Hospital.
Am J Surg Pathol. 2025 Apr 29;49(8):837-853. doi: 10.1097/PAS.0000000000002403.
In this study, we aimed to reclassify "round cell sarcomas" identified in the Department of Pathology, Istanbul Faculty of Medicine, Istanbul University, between 2013 and 2023, using an immunohistochemical panel including CD99, NKX2.2, ETV4, WT1, DUX4, BCOR, CCNB3, and SS18-SSX antibodies, fluorescence in situ hybridization (FISH), and next-generation sequencing (NGS). A total of 148 Ewing's sarcomas, 21 CIC::DUX4 sarcomas, and 18 BCOR::CCNB3 sarcomas were diagnosed. Histopathologic features such as pleomorphism, prominent nucleoli, wide clear/eosinophilic cytoplasm, myxoid/pink hyaline stroma, and spindle cell components were useful for differentiating the other two sarcomas from Ewing sarcoma. The intensity of CD99 antibody staining in CIC::DUX4 and BCOR::CCNB3 sarcomas varied. The NKX2.2 antibody was diffuse nuclear positive in 93% of Ewing sarcomas and negative in CIC::DUX4 and BCOR::CCNB3 sarcomas. The DUX4 antibody was diffuse nuclear positive in all CIC:DUX4 sarcomas. Survival in CIC::DUX4 sarcomas tended to be lower than in the other groups, although there was no statistically significant difference between the groups. The histopathologic regression response, indicating the histopathologic response to neoadjuvant therapy according to the Ewing sarcoma regimen, was similar among all three groups. For BCOR::CCNB3 sarcomas, the histopathologic regression response in patients treated with the Ewing regimen was as low as 30%, whereas those treated with non-Ewing regimens showed a higher histopathologic regression response of 70%. A tumor size of 5 cm and above was found to be a statistically significant negative factor for survival. Age, sex, and tumor location were not significant factors for survival.
在本研究中，我们旨在使用包括CD99、NKX2.2、ETV4、WT1、DUX4、BCOR、CCNB3和SS18 - SSX抗体的免疫组织化学检测组合、荧光原位杂交（FISH）和下一代测序（NGS），对2013年至2023年间在伊斯坦布尔大学伊斯坦布尔医学院病理科鉴定出的“圆形细胞肉瘤”进行重新分类。共诊断出148例尤因肉瘤、21例CIC::DUX4肉瘤和18例BCOR::CCNB3肉瘤。多形性、显著核仁、宽透明/嗜酸性细胞质、黏液样/粉红色透明基质和梭形细胞成分等组织病理学特征有助于将另外两种肉瘤与尤因肉瘤区分开来。CIC::DUX4和BCOR::CCNB3肉瘤中CD99抗体染色强度有所不同。NKX2.2抗体在93% 的尤因肉瘤中呈弥漫性核阳性，而在CIC::DUX4和BCOR::CCNB3肉瘤中呈阴性。DUX4抗体在所有CIC::DUX4肉瘤中呈弥漫性核阳性。CIC::DUX4肉瘤患者的生存率往往低于其他组，尽管各组之间无统计学显著差异。根据尤因肉瘤治疗方案评估的新辅助治疗组织病理学反应在所有三组中相似。对于BCOR::CCNB3肉瘤，接受尤因治疗方案的患者组织病理学缓解率低至30%，而接受非尤因治疗方案的患者组织病理学缓解率较高达70%。发现肿瘤大小5厘米及以上是生存的统计学显著负性因素。年龄、性别和肿瘤位置不是生存的显著因素。
