Classic Ewing Sarcoma of the Ankle With Ewing Sarcoma RNA-Binding Protein 1-Friend Leukemia Integration 1 (EWSR1/FLI1) Fusion: A Case Report and Review of Diagnostic Considerations

Ewing sarcoma (ES) is a malignant small round blue cell tumor most frequently arising in the long bones of adolescents and young adults, characterized by a translocation involving the Ewing sarcoma RNA-binding protein 1 (<i>EWSR1</i>) gene, most commonly the <i>EWSR1</i>/friend leukemia integration 1 (<i>FLI1</i>) fusion. We report a case of a 26-year-old man with left ankle pain found to have an extraosseous soft tissue mass surrounding the calcaneus. Histopathology revealed a highly cellular neoplasm of uniform small round blue cells arranged in sheets and nests, immunoreactive for cluster of differentiation 99 (CD99) with diffuse membranous staining and negative for AE1/AE3, desmin, CD45, and S100. Targeted next-generation sequencing confirmed an <i>EWSR1</i>/<i>FLI1</i> fusion, establishing the diagnosis of ES.