We evaluated the usefulness of immunohistological staining for S-100 protein in differentiating mammary and extramammary Paget's disease from primary malignant melanoma of superficial spreading (pagetoid) type. This technique was compared to both the mucicarmine and periodic acid-Schiff (PAS) methods. The tumor cells of 10 melanomas contained abundant cytoplasmic S-100 protein. In tissues from mammary and extramammary Paget's disease, S-100 protein was detected in myoepithelial cells, Langerhans cells, and Schwann cells of cutaneous nerves, but was not present in tumor cells. The mucicarmine stain was most useful for vulvar Paget's disease, mucicarminophilic material being present in 9/10 cases. In mammary Paget's disease, only 2/8 cases stained by the mucicarmine technique. Cytoplasmic PAS-positive material was present in the tumor cells of 9/10 cases of vulvar Paget's disease, but was noted in only 1/9 cases of mammary Paget's disease. Melanoma cells from two cases stained weakly with both mucicarmine and PAS indicating that these stains are not specific for Paget's disease in this comparison. The PAS and mucicarmine stains are helpful in differentiating anogenital Paget's disease from pagetoid melanoma, but are less useful in mammary Paget's disease. Immunohistological demonstration of S-100 protein provides an additional diagnostic tool to aid the separation of Paget's disease from pagetoid melanoma.
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