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A Chemotherapy Responsive Ewing Sarcoma Case Report With a Rare FUS::FLI1 Fusion.

Ismail M Elbaz Younes^1,2, G Thomas Budd³, Yu-Wei Cheng¹

¹Department of Laboratory Medicine, Cleveland Clinic, Cleveland, Ohio, USA.

Case Reports in Pathology

|August 27, 2025

Summary

This study reports a rare case of retroperitoneal Ewing sarcoma in a 42-year-old male with a FUS::FLI1 gene fusion. The patient responded well to chemotherapy, marking the first documented response for this specific Ewing sarcoma genetic subtype.

Keywords:

Ewing sarcoma FLI1 FUS NGS gene fusion

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Area of Science:

Oncology
Genetics
Pathology

Background:

Ewing sarcoma is an aggressive small round cell cancer primarily affecting adolescents and young adults.
It is characterized by specific gene fusions, most commonly involving EWSR1.
While typically bone-associated, it can occur in soft tissues.

Observation:

A 42-year-old male presented with retroperitoneal Ewing sarcoma.
Biopsy revealed a rare FUS::FLI1 gene fusion, a variant of the typical EWSR1 fusions.
The patient received chemotherapy for this retroperitoneal tumor.

Findings:

The patient with the rare FUS::FLI1 fusion demonstrated a positive response to chemotherapy.
This represents the first reported instance of chemotherapy efficacy in Ewing sarcoma with this specific genetic alteration.

Implications:

Chemotherapy may be an effective treatment option for Ewing sarcoma cases with the FUS::FLI1 fusion.
This finding expands treatment possibilities for rare Ewing sarcoma subtypes.
Further research into targeted therapies for FUS::FLI1-positive Ewing sarcoma is warranted.