[Cutaneous clear cell sarcoma]

Clear cell sarcoma is a rare, aggressive neoplasm with melanocytic differentiation, characterised by an EWSR1 fusion with ATF1, CREB1 or CREM. In addition to the classic deep-seated variant, a significantly rarer dermal/cutaneous form exists. First described in 2009, it is frequently misdiagnosed due to its histopathological and immunohistochemical overlap with melanoma.

This review aims to summarise the current state of knowledge on cutaneous clear cell sarcoma, including pathogenesis, histopathology, immunohistochemistry, molecular pathology and differential diagnoses, to raise awareness of this underdiagnosed entity.

A comprehensive literature search was conducted in PubMed/MEDLINE without time restrictions, focusing on clear cell sarcomas (specifically cutaneous cases) and CRTC1::TRIM11 cutaneous tumours. All English-language publications deemed relevant were evaluated regarding clinical, histopathological, immunohistochemical and molecular genetic features.

Approximately 55 cases of cutaneous clear cell sarcoma have been published to date; they are thus significantly rarer than classic deep-seated cases. They show a broader anatomical distribution, a smaller size, and a somewhat less aggressive course than the latter. They predominantly affect young adults with a female predominance. Histologically, they consist of fascicles and nests of epithelioid and spindled cells with melanocytic marker expression. PRAME is the only helpful immunohistochemical marker in the distinction from melanoma. The main differential diagnosis, besides melanoma, is the CRTC1::TRIM11 cutaneous tumour, which, based on current evidence, has a more favourable prognosis.

Molecular confirmation of the EWSR1 rearrangement is desirable for diagnosis, as the differentiation from other neoplasms, including melanoma and CRTC1::TRIM11 cutaneous tumours, has important therapeutic and prognostic consequences.