Cutaneous epithelioid sarcoma

Subtypes

• Classical (distal-type) — young adults (median 20–40), volar finger / hand / forearm; slow growth; multiple "satellite" nodules along fascia, tendon sheaths and lymphatics ("epithelioid sarcoma is the great mimic of a benign nodule").
• Proximal-type — middle age, trunk, pelvis, perineum, vulva; larger, more rapidly growing; rhabdoid morphology; substantially worse prognosis.

Clinical features

• Slow-growing, painless, firm dermal/subcutaneous nodule — often present for months to years before diagnosis.
• Frequently misdiagnosed as wart, plantar wart, ganglion, rheumatoid nodule, granuloma annulare, fibroma, foreign-body reaction.
• May ulcerate or bleed; multiple satellite nodules along the limb at diagnosis.
• Regional lymph-node metastasis is unusually common for a sarcoma (~30–50%).

Histology & molecular

• Nodular proliferation of large epithelioid and spindled cells with eosinophilic cytoplasm, often arranged around central necrosis (granuloma-like) — hence misdiagnosis as a granulomatous lesion.
• Proximal-type shows rhabdoid morphology with eccentric nuclei and paranuclear inclusions.
• Loss of SMARCB1 (INI1) nuclear staining in >90% — diagnostic hallmark.
• Cytokeratin (AE1/AE3) and EMA positive (mimicking carcinoma); CD34 positive (~50%); ERG positive (mimicking endothelial differentiation).

Management

• Sarcoma MDT involvement essential.
• Wide local excision with the largest feasible margins (often 2–3 cm); ray amputation or below-elbow amputation may be required for distal lesions.
• Regional lymph node assessment (clinical, USS or sentinel-node) given high nodal metastatic risk.
• Imaging — MRI of affected limb to map satellite spread; CT chest for pulmonary metastasis.
• Adjuvant radiotherapy reduces local recurrence, particularly with close/positive margins.
• Adjuvant chemotherapy controversial; doxorubicin/ifosfamide considered for high-grade or proximal-type disease.
• Tazemetostat — EZH2 inhibitor with phase 2 evidence in INI1-deficient advanced epithelioid sarcoma, but no positive NICE recommendation and no routine NHS commissioning route identified. Treat as a sarcoma-MDT / clinical-trials / exceptional-access discussion only; note the 2026 FDA safety alert and announced US market withdrawal after excess secondary haematological malignancies.
• Pembrolizumab and other immune checkpoint inhibitors are investigational / selected-case options only.

Prognosis

Local recurrence 30–80% (highest with conservative excision); regional or distant metastasis 30–50%; 5-year overall survival 60–70% for distal-type, 30–50% for proximal-type. Adverse factors: proximal subtype, large size, deep extension, lymphovascular invasion, nodal metastasis. Long-term surveillance for at least 10 years is essential — late recurrence is well described.