Synonyms

• Extraskeletal Ewing sarcoma
• soft tissue Ewing

Category

Soft tissue

Behaviour

Malignant

Grade

High

Gender

Male

Tissue of Origin

Neural crest / undifferentiated mesenchymal

Epidemiology

• 15% of all Ewing sarcoma tumours occur in soft tissue
• Peak incidence in 1st–2nd decades
• Slight Male predominance
• Identical molecular profile to Bone Ewing sarcoma

Clinical Features

• Rapidly growing painful soft tissue mass
• May arise at any site - paraspinal, chest wall, extremity
• Systemic symptoms less common than Bone Ewing
• Fever and elevated ESR/CRP in some cases

Location

• Paravertebral and chest wall
• Extremities (Lower > upper)
• Retroperitoneum
• Head and neck

Imaging

• Large heterogeneous soft tissue mass
• No Bone involvement in extraskeletal form
• MRI: heterogeneous, Variable necrosis
• FDG-avid on PET-CT

Pathology

• Small round blue cell tumour - uniform cells with little cytoplasm
• CD99 (MIC2) diffuse membranous positivity (essential)
• NKX2.2 nuclear positivity
• EWSR1 rearrangement (most commonly EWSR1-FLI1 or EWSR1-ERG)

Genetics

• EWSR1-FLI1 (t(11;22)(q24;q12)) in 85%
• EWSR1-ERG in 10%
• Other rare EWSR1 fusions (ETV1, ETV4, FEV)
• RNA sequencing may detect fusions not found by FISH

Treatment

• Multiagent chemotherapy: VAC/IE (vincristine, doxorubicin, cyclophosphamide alternating with ifosfamide, etoposide)
• Local control: surgery and/or radiotherapy
• High-dose chemotherapy with stem cell rescue for High-risk/metastatic disease
• Newer agents: TK216 (in trials)

Prognosis

• 5-year survival 60–70% for localised disease
• Metastatic disease: 25–30% 5-year survival
• Pulmonary metastasis most common
• Extraskeletal Ewing generally has similar prognosis to Bone Ewing

Key Points

• Extraskeletal Ewing sarcoma is biologically identical to Bone Ewing - treated with same protocols
• CD99 is Highly sensitive but not specific - EWSR1 FISH required for definitive diagnosis
• RNA-seq increasingly replacing FISH for fusion detection
• Large tumour volume and metastases at presentation are adverse prognostic factors

Workup - Blood Tests

• FBC, U&E, LFTs, Bone profile - baseline and pre-chemotherapy
• LDH - prognostic marker
• C-reactive protein, fibrinogen - baseline inflammatory markers

Workup - Local Imaging

• MRI primary site with gadolinium - local staging; heterogeneous soft tissue mass with Variable necrosis
• CT chest/abdomen/pelvis - metastatic staging (pulmonary metastases most common)
• PET-CT - FDG avid; systemic staging
• Bone scan or whole-body MRI - skeletal staging

Workup - Biopsy

• Core needle biopsy at sarcoma centre - en bloc excision of tract
• CD99 (MIC2) diffuse membranous+ (essential)
• EWSR1-FLI1 or EWSR1-ERG FISH - diagnosis confirmation (85% and 10%)
• RNA-seq if FISH negative - detects other EWSR1 fusions

Workup - Staging

• CT chest/abdomen/pelvis - metastases
• PET-CT - systemic staging

Follow-up Summary

• Years 1–2: 3–4 monthly clinical review + CXR; MRI primary site at 3 months post-op then 6-monthly
• CT chest every 3–4 months for first 2 years (pulmonary metastasis is primary concern)
• Years 3–5: 6-monthly clinical review + CXR; CT chest 6-monthly
• Years 6–10: Annual clinical review + CXR; CT chest annually
• Discharge at 10 years after treatment