Amelanotic melanoma: cases studied by Fontana stain, S-100 immunostain, and ultrastructural examination

We studied 15 cases of amelanotic melanoma by using light microscopy (in conjunction with Fontana staining and S-100 immunostaining) and electron microscopy. In 14 of the 15 cases, metastatic melanomas were present; 11 were associated with a history of pigmented primary melanoma. The Fontana stain was positive in 4 cases and negative in 11. The S-100 stain was positive in 13 cases and negative in 2. Of the 11 cases with negative Fontana stains, 9 were positive with the S-100 immunostain and 2 were negative. Electron microscopy showed melanosomes in 13 cases. Melanosomes were seen in the two cases with negative Fontana and S-100 staining. Although all stages of melanosomes were identified, generally the majority were immature melanosomes. This study demonstrates the difficulties associated with the histologic diagnosis of amelanotic melanoma. The Fontana stain may be helpful, and the S-100 stain is generally positive. Electron microscopy provided the only evidence for melanoma in two cases and is considered the most definitive method of diagnosis of amelanotic melanomas. These tumors generally produce some pigment and thus are called amelanotic by convention, not because pigmentation is totally absent.