# 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

## TL;DR

A 26-year-old man was diagnosed with Ewing sarcoma in his ankle after a biopsy and genetic testing confirmed the EWSR1/FLI1 fusion, a hallmark of this cancer.

## Contribution

This case report highlights the rare occurrence of Ewing sarcoma in the ankle and confirms the EWSR1/FLI1 fusion through next-generation sequencing.

## Key findings

- Histopathology showed a small round blue cell tumor with CD99 positivity and absence of other markers.
- Next-generation sequencing confirmed the presence of the EWSR1/FLI1 fusion gene.
- The case emphasizes the importance of genetic testing in diagnosing Ewing sarcoma in atypical locations.

## Abstract

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 (EWSR1) gene, most commonly the EWSR1/friend leukemia integration 1 (FLI1) 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 EWSR1/FLI1 fusion, establishing the diagnosis of ES.