Abstract

Desmoplastic melanoma is a melanoma subtype that typically arises on chronically sun-damaged skin in elderly patients and is known for being difficult to diagnose. Dedifferentiation in these tumors is rare and poorly understood, presenting additional diagnostic challenges. Previous reports of dedifferentiated melanoma variants are limited, with the dedifferentiated components showing undifferentiated sarcomatous, rhabdomyosarcomatous, and epithelial differentiation, or features resembling atypical fibroxanthoma. We report a case of desmoplastic melanoma with leiomyosarcomatous dedifferentiation in an 87-year-old male who presented with a lesion on the forearm. Histologic sections revealed a deeply infiltrative, poorly defined neoplasm characterized by SOX10-positive spindle-shaped melanocytes scattered within a fibromyxoid stroma, surrounded by discrete lymphoid aggregates. The overlying epidermis exhibited florid melanoma in situ, with focal nests of invasive melanoma in the papillary dermis displaying more conventional morphology. A morphologically distinct area demonstrated prominent fascicular architecture composed of atypical, blunted spindle cells with abundant mitotic figures. Immunohistochemistry of this area showed the lesional cells were positive for desmin and negative for melanocytic markers. Next-generation sequencing was performed on the two morphologically distinct areas, revealing that both the desmoplastic melanoma and leiomyosarcomatous regions shared identical KRAS and HRAS variants. This molecular relationship suggests a clonal origin, strongly indicating that the melanoma has undergone an area of dedifferentiation, rather than representing a "collision" of two different neoplasms. To our knowledge, leiomyosarcomatous dedifferentiation within a desmoplastic melanoma is exceedingly rare. Diagnosing these infrequent tumors requires extensive tumor sampling, careful recognition of an underlying but often subtle conventional melanoma, and molecular analysis.