S100, HMB-45, and Melan-A negative primary melanoma.

The diagnosis of malignant melanoma can be challenging given the wide variation in morphologic features and immunohistochemical stains are often used to confirm the diagnosis. We report a case of melanoma with loss of staining for S100 protein, HMB-45, and Melan-A, with retained expression of tyrosinase. Regional lymph node metastases showed positive S100 protein staining. Although the loss of phenotypic markers including S100 protein has been reported in metastatic melanoma, loss of S100 in primary melanoma is rare. Discordant staining between primary and metastatic lesions further emphasizes the protean nature of melanoma.