From the ashes of “Ewing-like” sarcoma: A contemporary update of the classification, immunohistochemistry, and molecular genetics of round cell sarcomas

Round cell sarcomas include a diverse group of bone and soft tissue tumors, which comprise well-defined entities as well as several nascent categories presented in the 2020 World Health Organization classification. The morphologic overlap yet disparate nosology, prognostic implications, and management strategies places a high value on ancillary testing, including a strategic immunohistochemical approach and directed confirmation by cytogenetic and molecular genetic methods. We review the diagnostic categories that have emerged from the former wastebasket "undifferentiated round cell sarcoma" ("Ewing-like" sarcomas), with an emphasis on algorithmic exclusion of nonsarcomatous entities, diagnostic stratification of well-defined entities (Ewing sarcoma, rhabdomyosarcomas, poorly differentiated synovial sarcoma), and a discussion of the new categories with novel genetic alterations (CIC-rearranged sarcomas, sarcomas with BCOR genetic alterations, and round cell sarcomas with EWSR1-non-ETS fusions).