Abstract

Desmoplastic melanomas (DM) and malignant peripheral nerve sheath tumors (MPNST) have long posed a diagnostic quandary to dermatopathologists. A 79-year-old male presented with a firm, hyperpigmented nodule on his right forearm present for 20 years with recent significant growth. Adjacent small growths had been present for many years and were stable. A partial punch biopsy revealed a spindle-cell neoplasm that stained for SOX10 and S100 but not for Melan-A, and excision was recommended. The excised specimen was initially diagnosed as amelanotic desmoplastic melanoma with extensive neural differentiation based on S100 and SOX10 positivity. Histopathologic examination revealed a spindled neoplasm in the dermis and subcutis, with a multinodular growth pattern and a background spindle cell proliferation suggestive of a background neurofibroma. Immunohistochemistry (IHC) showed patchy S100 and SOX10 positivity, diffuse positive pericellular staining for reticulin, retention of INI1, diffuse loss of H3K27ME3, and negative staining for Melan-A, CD34, CD68, desmin, and smooth muscle actin. Biopsies of adjacent smaller growths were consistent with multiple neurofibromas. He was eventually diagnosed with cutaneous MPNST (c-MPNST) in association with segmental neurofibromatosis (NF5). This case represents a rare presentation of c-MPNST developing in association with segmental NF and highlights the diagnostic challenges in distinguishing between DM and MPNST. This distinction is crucial given the differences in both prognosis and management. There are significant overlapping histopathologic and immunohistochemical findings between the two entities. Although not always present, clues including an intraepidermal component (lentigo maligna), diffuse versus patchy S100 and SOX10 staining, association with neurofibromas, as well as loss of H3K27Me3 may help distinguish the two entities.

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