Paper II
Question
Describe the genetic basis, radiological findings and morphology of Ewing Sarcoma
Answer
Ewing sarcoma is a highly malignant small round blue cell tumour of bone (and soft tissue), most commonly affecting children and adolescents.
Genetic basis
- Characteristic reciprocal translocation, most commonly t(11;22)(q24;q12), fusing the EWSR1 gene (chromosome 22) with the FLI1 gene (chromosome 11), producing the EWS-FLI1 fusion oncoprotein, an aberrant transcription factor that drives uncontrolled proliferation
- This translocation is found in the vast majority of cases and is used diagnostically (FISH/RT-PCR)
Radiological findings
- Typically arises in the diaphysis of long bones (e.g., femur) or flat bones (pelvis)
- Permeative, moth-eaten lytic bone destruction
- Classic “onion-skin” periosteal reaction — multiple layers of reactive periosteal new bone formation, reflecting repeated episodes of tumour breaking through and stimulating periosteal reaction
- Associated soft tissue mass often present
Morphology
Gross
- Grey-white, soft, friable tumour, often with extensive haemorrhage and necrosis, extending into surrounding soft tissue
Microscopic
- Sheets of small, uniform round cells with scant cytoplasm and round nuclei with fine (“salt and pepper”) chromatin
- High nuclear:cytoplasmic ratio
- Cells contain glycogen (PAS-positive, diastase-sensitive)
- Immunohistochemistry: strongly positive for CD99 (MIC2 gene product) — a characteristic (though not entirely specific) marker; FLI1 positivity supports the diagnosis