Compound clear cell sarcoma with EWSR1::CREM fusion

Abstract

AbstractCutaneous clear cell sarcomas may be confused with melanomas as a result of overlapping histopathology and immunohistochemical staining. We report a case of a 41‐year‐old woman with a purported history of acral melanoma of the great toe. Twenty‐one months after excision of the primary tumor, the patient developed a groin mass, diagnosed as metastatic melanoma on excision. Five months later, a biopsy of a lung mass was reported as metastatic melanoma. The patient was referred to our institution for treatment, which prompted molecular testing on the groin metastasis by targeted next‐generation sequencing. Molecular testing results revealed TP53 and TERT promoter mutations and the absence of BRAF, KRAS, and KIT mutations; it also revealed an EWSR1::CREM fusion that was confirmed by Archer FusionPlex. The alleged acral melanoma was re‐reviewed, showing an invasive amelanotic spindle cell neoplasm in the dermis with neoplastic nests at the dermal–epidermal junction; the tumor cells expressed markers of melanocytic differentiation but were negative for PRAME and BRAF immunohistochemical staining. Molecular testing of the toe and lung metastasis revealed the same EWSR1::CREM fusion. In light of the molecular findings, the diagnosis was revised to a primary acral compound clear cell sarcoma with EWSR1::CREM fusion.