S-100 PROTEIN NEGATIVE MALIGNANT-MELANOMA - FACT OR FICTION - A LIGHT-MICROSCOPIC AND IMMUNOHISTOCHEMICAL STUDY

S-100 protein is considered a characteristic immunohistochemical marke r for all nevomelanocytic lesions, in which it is expected to be prese nt consistently. We reviewed 17 cases of malignant melanomas that prev iously tested negative for S-100 protein. They were reevaluated by lig ht microscopy, a broad panel of immunohistochemical reagents including monoclonal and polyclonal antibodies to S-100 protein, and electron m icroscopy. On reexamination, five of the 17 cases were reclassified as non-melanoma tumors, and eight of the 17 cases were found to be posit ive for S-100 protein (six with monoclonal and eight with polyclonal a ntibodies) and HMB-45 antigen, consistent with melanoma. The remaining four cases repeatedly tested negative for S-100 protein despite vario us antigen enhancement methods, but they were positive for HMB-45 anti gen and contained premelanosomes or melanosome-like structures by elec tron microscopy. Two of these repeatedly S-100 negative melanomas were acrally located; although the numbers are small, a possible relations hip to a specific anatomic location cannot be excluded. These findings suggest that in a small subset of melanomas S-100 protein is either n ot fully expressed or is below the level that can be detected by routi ne immunohistochemistry. We also conclude that in the majority of the initially S-100-negative cases of melanomas, the misdiagnosis may occu r due to the use of an incomplete immunohistochemical panel, technical reasons, or the inherent variability of tissue expression of S-100 pr otein.