VERY-RARE CANCERSarcomaWHO 5th Edition Classification

Clear Cell Sarcoma

Very Rare Malignancy (1–5 cases per 1,000,000 / year) • Clinical Staging, Genomic Targets & Vetted Specialists

A rare soft-tissue sarcoma of tendons and aponeuroses, historically called melanoma of soft parts because it produces melanin and expresses melanocytic markers. It is nonetheless a sarcoma, defined by the EWSR1-ATF1 fusion, and unlike cutaneous melanoma it responds poorly to checkpoint inhibitors.

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Who It Affects

Young adults, typically 20-40 years

Annual Incidence

Under 1% of soft-tissue sarcomas

Clinical Evidence Review

Last audited: 2026-08-13 against NCCN, ESMO, and WHO 5th ed. guidelines.

Clinical Presentation & Hallmark Symptoms

Presenting signs most frequently observed across clinical case series

A slowly growing, deep-seated lump near a tendon, usually foot, ankle or knee
Pain or tenderness in about half of patients
Restricted joint movement
Regional lymph node enlargement - nodal spread is characteristic
Long history before diagnosis is common

Genomic Profiling & Defining Molecular Lesions

Critical diagnostic fusions, somatic mutations, and therapeutic targets

Rare malignancies frequently depend on distinct oncogenic drivers rather than conventional environmental carcinogens. Comprehensive Next-Generation Sequencing (NGS comprehensive panel) and FISH/IHC are mandatory to establish the true diagnosis and screen for basket trial agents.

EWSR1-ATF1 fusion, t(12;22)(q13;q12)EWSR1-CREB1 - variantS100/HMB45/MelanA positive

Standard-of-Care Treatment Protocol

Frontline and multimodal strategies established under international consensus guidelines

1

Wide surgical excision with negative margins - the mainstay

Administered in specialized high-volume oncology programs with subspecialty pathology and organ-preservation protocols.

2

Sentinel node biopsy or regional lymph node assessment

Administered in specialized high-volume oncology programs with subspecialty pathology and organ-preservation protocols.

3

Adjuvant radiotherapy for close margins or large tumours

Administered in specialized high-volume oncology programs with subspecialty pathology and organ-preservation protocols.

4

MET inhibitors and antiangiogenic TKIs in advanced disease (trial setting)

Administered in specialized high-volume oncology programs with subspecialty pathology and organ-preservation protocols.

5

Conventional chemotherapy has limited activity

Administered in specialized high-volume oncology programs with subspecialty pathology and organ-preservation protocols.

Clinical Trial Advisory: For rare and ultra-rare malignancies, enrollment in an active clinical trial or expanded-access program is widely considered the preferred standard of care by ASCO and NCCN panels.

Prognosis & Disease Trajectory

Objective clinical outlook without false reassurance

Guarded. Five-year survival is roughly 50-65% overall but falls substantially with tumours over 5 cm, necrosis or nodal involvement. Late relapse beyond ten years is well described, so surveillance must be long.

Note: Statistics reflect cohort averages. Individual outcomes depend heavily on performance status, resectability, biomarker expression, and timely access to specialized tertiary care.

Active Research, Biomarkers & Clinical Trials

Novel investigational agents, phase I/II trials, and international rare disease consortia

MET pathway inhibition, given ATF1-driven MET upregulation, and EWSR1-ATF1-directed approaches are the principal research strategies.

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Expert Clinicians

Verified Specialists for Clear Cell Sarcoma

Browse All Oncologists

Dr. Mark Dickson

Medical Oncologist

15+ yrs exp

MSKCC

New York, USA

Rare SarcomasClear Cell SarcomaImmunotherapy
Vetted DirectoryConsult Specialist

Dr. Wong Seng Weng

Medical Oncologist

20+ yrs exp

Parkway Cancer Centre

Singapore, Singapore

Melanocytic Clear Cell SarcomaNovel AgentsSarcoma
Vetted DirectoryConsult Specialist

Prof. Paolo Casali

Medical Oncologist

30+ yrs exp

Istituto Nazionale Tumori (INT)

Milan, Italy

Sarcoma OncologyClear Cell SarcomaSystemic Therapy
Vetted DirectoryConsult Specialist

Dr. Sameer Rastogi

Sarcoma Medical Oncologist

15+ yrs exp

AIIMS, New Delhi

New Delhi, India

Sarcoma ClinicClear Cell SarcomaTargeted Therapy
Vetted DirectoryConsult Specialist
Hospital Network

Designated Cancer Centers with Dedicated Programs

Search All 72 NCI Centers

Memorial Sloan Kettering Cancer Center

NY

NCI-Designated Comprehensive Cancer Center

World-leading rare tumor board & pediatric solid tumor protocols

Proton TherapyCAR-T Cell TherapyRobotic Surgery
1,000+ Active Clinical TrialsView Center Profile

University of Texas MD Anderson Cancer Center

TX

NCI-Designated Comprehensive Cancer Center

Largest specialized rare cancer and sarcoma multidisciplinary program

Proton TherapyCAR-T Cell TherapyCyberKnife SBRT
1,200+ Active Clinical TrialsView Center Profile

Dana-Farber / Harvard Cancer Center

MA

NCI-Designated Comprehensive Cancer Center

Pioneering genomic molecular tumor boards & rare histologies

Proton TherapyCAR-T Cell TherapyPhase I Unit
1,100+ Active Clinical TrialsView Center Profile

Mayo Clinic Comprehensive Cancer Center

MN

NCI-Designated Comprehensive Cancer Center

High-volume surgical oncology & rare endocrine/neuroendocrine expertise

Proton TherapyCAR-T Cell TherapyCyberKnife SBRT
600+ Active Clinical TrialsView Center Profile

Frequently Asked Clinical Questions

Authoritative guidance on diagnosis, tumor boards, genomic markers, and care options

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Independent Tumor Board Review

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