Variable Expression of S100 Protein in Sinonasal Malignant Mucosal Melanoma: A Potential Diagnostic Pitfall - PubMed (original) (raw)
Variable Expression of S100 Protein in Sinonasal Malignant Mucosal Melanoma: A Potential Diagnostic Pitfall
Xiang Xu et al. Head Neck Pathol. 2020 Dec.
Abstract
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.
Keywords: Malignant mucosal melanoma; S100 protein; SOX10; Sinonasal tract; Small round blue cell tumor.
Conflict of interest statement
All authors declare that he/she has no conflict of interest as it relates to this research project.
Figures
Fig. 1
Case 6 was a sinonasal melanoma with melanin pigment (a). This example was diffusely and strongly positive for both S100 protein (b) and SOX10 (c), as expected for melanoma
Fig. 2
Case 13 was an amelanotic small round cell tumor (a) that was only focally and weakly positive for S100 protein (b), but strongly and diffusely positive for SOX10 (c)
Fig. 3
Case 8 was an example of sinonasal melanoma that consisted of undifferentiated appearing small round cells with abundant hemorrhage (a). S100 protein was completely negative. Note the small nerve that served as a positive internal control (b). SOX10 immunostaining, on the other hand, was strong and diffuse in both the tumor and the small nerve (c)
Fig. 4
Case 23 was an unusual sinonasal melanoma with areas showing pink matrix-like material, resembling osteoblastic or chondroblastic differentiation (a). These portions of the tumor were focally and strongly positive for both S100 protein (b) and SOX10 (c). Other areas of the tumor were composed of small round cells difficult to separate from lymphocytes. Melanin pigment was noted in these areas (d). These areas showed very limited S100 protein staining (e), but were strongly positive for SOX10 (f)
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