title: S-100 protein-negative malignant melanoma: fact or fiction? A light-microscopic and immunohistochemical study.
abstract: S-100 protein is considered a characteristic immunohistochemical marker for all nevomelanocytic lesions, in which it is expected to be present consistently. We reviewed 17 cases of malignant melanomas that previously tested negative for S-100 protein. They were reevaluated by light microscopy, a broad panel of immunohistochemical reagents including monoclonal and polyclonal antibodies to S-100 protein, and electron microscopy. On reexamination, five of the 17 cases were reclassified as non-melanoma tumors, and eight of the 17 cases were found to be positive for S-100 protein (six with monoclonal and eight with polyclonal antibodies) and HMB-45 antigen, consistent with melanoma. The remaining four cases repeatedly tested negative for S-100 protein despite various antigen enhancement methods, but they were positive for HMB-45 antigen and contained premelanosomes or melanosome-like structures by electron microscopy. Two of these repeatedly S-100 negative melanomas were acrally located; although the numbers are small, a possible relationship to a specific anatomic location cannot be excluded. These findings suggest that in a small subset of melanomas S-100 protein is either not fully expressed or is below the level that can be detected by routine immunohistochemistry. We also conclude that in the majority of the initially S-100-negative cases of melanomas, the misdiagnosis may occur due to the use of an incomplete immunohistochemical panel, technical reasons, or the inherent variability of tissue expression of S-100 protein.
authors.affiliation: Department of Pathology, University of Iowa Hospitals and Clinics, Iowa City 52242-1009.
authors.forename: Z B
authors.initials: ZB
authors.lastname: Argenyi
authors.forename: C
authors.initials: C
authors.lastname: Cain
authors.forename: C
authors.initials: C
authors.lastname: Bromley
authors.forename: A V
authors.initials: AV
authors.lastname: Nguyen
authors.forename: A A
authors.initials: AA
authors.lastname: Abraham
authors.forename: R
authors.initials: R
authors.lastname: Kerschmann
authors.forename: P E
authors.initials: PE
authors.lastname: LeBoit
mesh_terms: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor / Q000032:analysis; D003951:Diagnostic Errors; D006801:Humans; D007150:Immunohistochemistry; D008545:Melanoma / Q000737:chemistry* / Q000175:diagnosis / Q000473:pathology / Q000648:ultrastructure; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins / Q000032:analysis; D009418:S100 Proteins / Q000032:analysis*; D012878:Skin Neoplasms / Q000737:chemistry* / Q000175:diagnosis / Q000473:pathology / Q000648:ultrastructure
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins; D009418:S100 Proteins