Ewing Sarcoma

What it is

Overview

Ewing sarcoma is a highly malignant bone and soft tissue cancer that primarily affects children and young adults. Unlike most cancers, Ewing sarcoma is defined by a specific chromosomal translocation: t(11;22) producing the EWSR1-FLI1 fusion protein in ~85% of cases. This discovery has been critical for diagnosis and offers a unique therapeutic target.

Biology

How It Develops

The hallmark EWSR1-FLI1 fusion acts as an aberrant transcription factor, dysregulating hundreds of target genes and blocking normal cell differentiation. This creates rapidly proliferating tumor cells that can arise in bone or soft tissue. The pelvis and long bones are most commonly affected. Micrometastases are present at diagnosis in most patients, even when imaging appears localized.

Warning signs

Symptoms

• —Pain and swelling at tumor site
• —Fever and fatigue
• —Weight loss
• —Fracture through a weakened bone

Detection

Diagnosis Methods

• —MRI and CT of the primary tumor
• —CT chest and bone scan/PET for staging
• —Biopsy with cytogenetics (FISH for EWSR1 rearrangement)
• —Bone marrow biopsy
• —RT-PCR for fusion transcript

Medical care

Treatment Options

• —Induction chemotherapy (VDC/IE: vincristine, doxorubicin, cyclophosphamide / ifosfamide, etoposide)
• —Local control: surgery and/or radiation
• —Consolidation chemotherapy
• —High-dose chemotherapy with stem cell rescue for high-risk disease
• —Clinical trials targeting EWSR1-FLI1

Data

Statistics

Prevention

Risk Factors

• —Age 10–20 (peak incidence)
• —Non-Hispanic white ethnicity (rare in Black and Asian populations)
• —No known modifiable risk factors

Further reading

Resources