Abstract

We report an unusual case of combined pattern epithelioid and desmoplastic melanoma metastases. A 58-year-old male with history of a T2a melanoma developed multiple cutaneous metastases. Each cutaneous biopsy from the metastases demonstrated the same biphenotypic pattern. Initial biopsy of a papule on the scalp showed junctional and dermal nests of atypical epithelioid melanocytes consistent with nodular melanoma, positive for SOX10, MART1, MITF, and PRAME. Deeper in the dermis was a distinct population of spindle cells in a sclerotic stroma with angiotropism and perineural invasion also positive for SOX10 typical of a desmoplastic melanoma. The superficial and deep components were laser microdissected apart for next generation sequencing. Both superficial and deep components exhibited the same NRAS Q61K mutation, the same loss of CDKN2A, high tumor mutational burden (TMB~18-20), and 18 of 20 shared variants of unknown significance.  A biopsy of a newly developed metastasis from the trunk showed an identical biphenotypic pattern and had a common mutational pattern with the same NRAS Q61K mutation and loss of CDKN2A.  The patient also developed metastases to the lung, thyroid, pancreas, axillary lymph nodes, liver, and kidney.  A biphenotypic epithelioid and spindle pattern of melanocytic tumors has been well reported in primary melanomas but our case is unique in that multiple metastases shared this distinct pattern.  In this report, we raise awareness that cutaneous metastases may also show a distinct biphenotypic patten with a nodular and desmoplastic melanoma component.  Our case is unique, showing multiple metastases with this same pattern.