Melanoma is the most common malignant tumor in which melanin synthesis occurs, although other nonmelanocytic tumors synthesize melanin or contain nonneoplastic melanocytes. We present two cases of infiltrating pigmented squamous cell carcinoma of the skin and review the clinical, morphologic, and ultrastructural features. Melanin was found in epithelial tumor cells as well as in macrophages and dendritic melanocytes. Interestingly, one of the neoplasms was associated with an adjacent melanocytic nevus and pigmented solar keratosis. Immunohistochemical analysis showed that neoplastic cells stained for keratin and melanin-filled dendritic cells were found to be S-100 protein and HMB45 positive. A careless examination of the immunohistochemical stains for S-100 protein and HMB45 could cause the misdiagnosis of melanoma, a neoplasm that has a more ominous outlook.

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