Undifferentiated Small Round Cell Sarcomas: Radiologic-Pathologic Correlation for the Updated WHO Classification Fifth Edition (2020)

The World Health Organization introduced substantial revisions in the 2020 fifth edition of the classification system for bone and soft-tissue tumors, reorganizing what were previously called the Ewing sarcoma family of tumors or Ewing-like sarcomas into a new category of "undifferentiated small round cell sarcomas" based on molecular genetic characteristics. This reclassification established four distinct entities: Ewing sarcoma (ES), <i>CIC</i>-rearranged sarcoma, sarcoma with <i>BCOR</i> genetic alterations, and sarcoma with <i>EWSR1-</i>non<i>-ETS</i> fusion genes. Each subtype may demonstrate specific clinical, pathologic, and imaging features, with different treatment responses and prognoses. ES primarily affects children and young adults, with characteristic "moth-eaten" lytic bone destruction, aggressive periosteal reactions, and extensive surrounding soft-tissue masses. <i>CIC</i>-rearranged sarcomas typically manifest as well-circumscribed lobulated soft-tissue masses with extensive internal necrosis and hemorrhage but no calcification. Sarcomas with <i>BCOR</i> genetic alterations commonly occur in adolescent boys as osteolytic or sclerotic lesions in the long bones or the pelvis, often with calcification in the extraosseous component. Sarcomas with <i>EWSR1-</i>non<i>-ETS</i> fusion genes may manifest as osteolytic lesions with cortical expansion and saucer-like surface erosion in long bone diaphyses. Radiologic recognition of <i>CIC</i>-rearranged sarcomas enables oncologists to anticipate their aggressive nature and poor response to standard ES treatments, which may necessitate more intensive initial surgical interventions. In comparison, identifying <i>BCOR-CCNB3</i> sarcomas through imaging allows clinicians to inform patients of their potentially more favorable outcomes compared with those of ES while still applying appropriate comprehensive treatment approaches. The authors provide an overview of the clinical features, pathologic findings, imaging characteristics, differential diagnosis, and treatment outcomes of each entity. ^©RSNA, 2026.