S-100, tyrosinase, Melan A, and HMB 45 have been the workhorses of melanocyte histopathology. A new immunohistochemical stain, SOX10, has recently been shown to be a useful marker in the diagnosis of melanocytic tumors. It is strongly expressed by desmoplastic melanoma and is less likely to be expressed by background fibrocytes and histiocytes.
Sry-related HMG-BOX gene 10 (SOX10), a nuclear transcription factor that plays an important role in schwannian and melanocytic cell differentiation, has recently been shown to be a useful marker in the diagnosis of melanocytic and schwannian tumors. Fibroblasts and histiocytes that can histologically mimic melanoma cells frequently express S100, which complicates the evaluation of melanoma excision specimens for residual tumor. SOX10 is strongly expressed by desmoplastic melanoma and less likely than S100 and MiTF to be expressed by background fibrocytes and histiocytes within scars.
Microphthalmia transcription factor (MiTF) is a melanocytic nuclear protein that is a highly sensitive and specific melanocyte marker. Although MiTF does not distinguish benign from malignant melanocytic lesions, for invasive melanomas it appears to be it is a great complement to H&E histopahtology.