Synonyms

• Melanoma of soft parts
• clear cell sarcoma of tendons and aponeuroses

Category

Soft tissue

Behaviour

Malignant

Grade

High

Gender

Both equally

Tissue of Origin

Neural crest (melanocytic differentiation)

Epidemiology

• Rare, 1% of soft tissue sarcomas
• Peak incidence in young adults (2nd–4th decades)
• No significant sex predilection
• Association with tendons and aponeuroses

Clinical Features

• Slowly growing deep soft tissue mass, often attached to tendon
• Pain or tenderness in 50%
• Often misdiagnosed as Benign nodule initially
• May have satellite nodules

Location

• Foot and ankle (most common)
• Lower extremity (knee, tHigh)
• Upper extremity
• Deep to skin, attached to tendons/fascia

Imaging

• Well-defined deep mass on MRI
• Iso- to hypointense on T1, heterogeneous on T2
• Variable enhancement
• FDG-avid on PET-CT

Pathology

• Nests of clear/pale cells with vesicular nuclei
• Melanin pigment in 50%
• S100, HMB45, melan-A positive (melanocytic differentiation)
• EWSR1-ATF1 or EWSR1-CREB1 fusion gene

Genetics

• EWSR1-ATF1 fusion (90%)
• EWSR1-CREB1 fusion (10%)
• These distinguish from melanoma (which lacks EWSR1 rearrangement)

Treatment

• Wide local excision with clear margins
• Sentinel lymph node biopsy considered (lymph node metastasis more common than other STS)
• Chemotherapy limited activity
• Targeted therapy: NTRK inhibitors, checkpoint inhibitors - under evaluation

Prognosis

• 5-year survival 50%
• Lymph node and distant metastasis common
• Late metastasis possible
• Prognosis worse than melanoma stage-for-stage

Key Points

• Distinct entity from cutaneous melanoma despite similar IHC profile
• EWSR1 rearrangement essential for diagnosis - melanoma lacks this
• Lymph node involvement more common than most STS - sentinel node biopsy should be considered
• Foot/ankle location in young adults is characteristic

Workup - Blood Tests

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

Workup - Local Imaging

MRI primary site with gadolinium - local staging

Workup - Biopsy

• Core needle biopsy - confirm diagnosis
• IHC: S100+, Melan-A+, HMB-45+, SOX10+ (melanoma-like profile)
• EWSR1-ATF1 FISH (t(12;22)) - present in 90%; diagnostic
• Histology: nested clear cells with nested architecture

Workup - Staging

• CT chest/abdomen/pelvis - metastatic disease
• PET-CT - staging

Workup - Other

• MDT at soft tissue sarcoma centre
• Melanoma-like immunophenotype - diagnose by molecular EWSR1-ATF1 fusion

Follow-up Summary

• Post-op visit at 6 weeks
• Year 1–2: 3–4 monthly clinical review + CXR; MRI primary site at 3 months then 6-monthly
• CT chest every 3–4 months for 2 years; consider lymph node surveillance (LN metastasis >30%)
• Sentinel lymph node biopsy results guide regional surveillance strategy
• Year 3–5: 6-monthly clinical review + CXR; CT chest 6-monthly
• Year 6–10: Annual clinical review + CXR; CT chest annually
• Discharge at 10 years; late metastasis recognised - advise self-monitoring