Compound clear cell sarcoma with EWSR1::CREM fusion

Area of Science:

• Oncology
• Molecular Pathology
• Dermatopathology

Background:

• Cutaneous clear cell sarcomas (CCCS) can mimic melanomas due to overlapping histopathology and immunohistochemistry.
• Accurate diagnosis is crucial for appropriate patient management and treatment strategies.

Observation:

• A patient initially diagnosed with acral melanoma developed metastatic disease.
• Initial histopathology and immunohistochemistry were suggestive of melanoma.
• Molecular testing revealed an EWSR1::CREM fusion and specific mutations (TP53, TERT promoter).

Findings:

• Re-evaluation of the primary and metastatic lesions alongside molecular data identified an EWSR1::CREM fusion.
• The tumor was reclassified as a primary acral compound clear cell sarcoma.
• Absence of BRAF, KRAS, and KIT mutations, along with negative PRAME and BRAF immunohistochemistry, supported the revised diagnosis.

Implications:

• Molecular profiling, particularly fusion detection, is essential for diagnosing challenging cutaneous neoplasms.
• This case underscores the utility of next-generation sequencing in revising diagnoses of suspected melanomas.
• Accurate classification of CCCS with EWSR1::CREM fusion impacts understanding of its pathogenesis and treatment.