Zb. Argenyi et al., S-100 PROTEIN NEGATIVE MALIGNANT-MELANOMA - FACT OR FICTION - A LIGHT-MICROSCOPIC AND IMMUNOHISTOCHEMICAL STUDY, The American journal of dermatopathology, 16(3), 1994, pp. 233-240
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.