The Extensive Case Series of 21 CIC::DUX4, 18 BCOR::CCNB3 and 148 Ewing’s Sarcomas From a Single Center

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.