Variable Expression of S100 Protein in Sinonasal Malignant Mucosal Melanoma: A Potential Diagnostic Pitfall

Sinonasal malignant mucosal melanoma (SNM) is a rare, aggressive malignancy. The diagnosis of SNM is often quite challenging due to anatomical limitations, frequent lack of pigmentation, variable histologic appearances, and aberrant differentiation (e.g., positivity for cytokeratin, desmin, or neuroendocrine markers). S100 protein is routinely used as a standard screening marker for SNM, but it may lack optimal sensitivity. Our objective was to study the extent of immunohistochemical expression of S100 protein in SNM, and determine its diagnostic value by comparing it to a newer melanoma marker, SOX10. Twenty-three cases of sinonasal MMM were retrieved from the archival files of the Department of Pathology at UT Southwestern Medical Center. The patients included 14 men and 9 women, and ranged from 36 to 90 years (mean 64.9 years). Sections from blocks of formalin-fixed, paraffin-embedded tissue were used for immunohistochemical analysis with S100 protein and SOX10. The extent and intensity of immunostaining was recorded, and H-score was calculated. For a subset of negative or focally positive cases, S100 protein was repeated at a high-volume reference laboratory. S100 protein immunoexpression was quite variable in the SNM cases, with H-scores ranging from 0 to 300 (mean 123). While 11 of 23 cases exhibited strong and diffuse staining (H-score > 100) as expected for melanoma, 7 were weak and/or focal (H-score 1-100), and 5 were completely S100 protein-negative. For 10 cases, the negative or focal results were confirmed by reference laboratory staining. In contrast, all 23 SNM cases were diffusely and strongly positive for SOX10 (H-scores 210-300, mean 296). Our study demonstrated that S100 protein immunoexpression is extremely variable in SNM. Weak or even absent S100 protein staining is not uncommon in SNM, and should not dissuade pathologists from that diagnosis. Our data demonstrates that S100 protein is insufficiently sensitive to be used as a screening marker for SNM, but that SOX10 is consistently and robustly positive, and should therefore replace S100 protein for that purpose. Indeed, for any high-grade sinonasal tumor, pathologists must have a low threshold for utilizing additional markers to exclude the possibility of SNM.