Epidermotropic Metastatic Melanoma Presenting as Eruptive Primary Melanomas

We report on the use of molecular profiling to diagnose epidermotropic metastatic melanoma (EMM) in a patient who presented with eruptive primary melanomas. On histopathology, the patient's metastatic lesions resembled superficial spreading melanomas and were indistinguishable from independent primary melanomas. The patient's presumed primary melanoma was a stage IIIB nodular melanoma. Despite treatment with adjuvant nivolumab, the patient continued to form new superficial spreading melanomas. Due to suspicion for EMM, commercial panel sequencing was performed on tissue from four tumors. Comparison of reported somatic variants revealed a mutational profile that was conserved across all four lesions, establishing a diagnosis of stage IV EMM. Considering the progressive disease on immunotherapy, treatment was transitioned to encorafenib plus binimetinib, resulting in regression of existing lesions and cessation of new skin lesion formation. Aside from micrometastatic sentinel lymph node deposits from the presumed primary melanoma, the patient had no evidence of non-cutaneous metastases. EMM should be considered as a diagnosis for multiple superficial spreading melanomas arising synchronously or in rapid succession. As EMM and primary melanomas are often histopathologically indistinguishable, next generation sequencing is a valuable tool to confirm clonality and provide a definitive diagnosis.