Synonyms

• Classic epithelioid sarcoma
• proximal-type epithelioid sarcoma

Category

Soft tissue

Behaviour

Malignant

Grade

High

Gender

Male (2:1)

Tissue of Origin

Unknown mesenchymal

Epidemiology

• Rare, <1% of soft tissue sarcomas
• Classic type: young adults, 2nd–4th decades
• Proximal type: middle-aged adults, more aggressive
• Associated with SMARCB1/INI1 loss

Clinical Features

• Classic: Slow-growing nodule(s) on fingers/hand/distal extremity, may ulcerate
• Proximal type: deep-seated pelvic/perineal mass
• Regional lymph node metastasis in 30–50%
• Tendency to spread along fascial planes

Location

• Classic: distal upper extremity (finger, hand, wrist, forearm)
• Proximal: pelvis, perineum, genital region
• Rare: trunk, head/neck

Imaging

• Multiple subcutaneous nodules on MRI (classic type)
• Deep heterogeneous mass (proximal type)
• Regional lymph node involvement
• Calcification in 20%

Pathology

• Nodular granuloma-like areas of central necrosis surrounded by epithelioid cells
• Epithelioid cells with eosinophilic cytoplasm
• Loss of INI1 (SMARCB1) by IHC - diagnostic
• Cytokeratin, EMA, vimentin positive; focal CD34 in 50%

Genetics

• SMARCB1 (INI1) inactivation - deletion or mutation
• Homozygous deletion of SMARCB1 in most cases
• Complex genomic profile in proximal type

Treatment

• Wide local excision with negative margins
• Amputation considered for locally unresectable distal extremity lesions
• Tazemetostat (EZH2 inhibitor) - FDA approved for SMARCB1-deficient epithelioid sarcoma
• Chemotherapy: doxorubicin/ifosfamide with modest activity

Prognosis

• 5-year survival 50–70% for classic type
• Proximal type: worse prognosis, 25–50% 5-year survival
• Lymph node and pulmonary metastasis common
• Local recurrence rate High

Key Points

• Loss of INI1 (SMARCB1) on IHC is diagnostically key
• Tazemetostat (EZH2 inhibitor) is the first targeted therapy approved for this disease
• Proximal type is more aggressive and carries worse prognosis than distal/classic type
• Lymph node dissection or sentinel node biopsy should be considered

Workup - Blood Tests

FBC, U&E, LFTs - baseline and pre-chemotherapy

Workup - Local Imaging

MRI with contrast primary site - nodular lesions; often multifocal along tendon sheaths

Workup - Biopsy

• Core needle biopsy - confirm diagnosis
• IHC: cytokeratin+, EMA+, FLI1+ (unusual in epithelioid tumours); INI1 LOSS (BAF47 negative) is diagnostic
• SMARCB1/INI1 FISH or immunostain showing loss - required for diagnosis
• Histology: nodules of epithelioid cells with central fibrinoid necrosis

Workup - Staging

• CT chest/abdomen/pelvis - metastases common (50% at diagnosis)
• PET-CT - staging

Workup - Other

• MDT at specialist soft tissue sarcoma centre
• INI1 loss is pathognomonic - confirms diagnosis
• High metastatic risk - multimodal therapy standard

Follow-up Summary

• Years 1–2: 3–4 monthly clinical review + CXR; MRI primary site 6-monthly
• CT chest every 3–4 months for first 2 years (pulmonary metastasis surveillance)
• Sentinel lymph node biopsy results guide lymph node surveillance strategy (LN mets in 30–50%)
• Years 3–5: 6-monthly clinical review + CXR; CT chest 6-monthly
• Years 6–10: Annual clinical review + CXR; CT chest annually
• Tazemetostat therapy monitoring: routine bloods and toxicity review at each visit
• Discharge at 10 years; advise lifelong self-monitoring