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Abstract

Distinguishing sebaceous neoplasms from histologic mimics such as basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) can be challenging. While adipophilin and androgen receptor (AR) are described in the literature, neither is sufficiently discriminatory alone. We evaluated whether STAT6 and PMS2, chosen for their distinct staining patterns in pilot observations and because they are more available than other reported sebaceous markers, could improve diagnostic accuracy. One hundred cases were selected: 75 sebaceous neoplasms (20 sebaceous carcinoma, 39 sebaceous adenoma, 11 sebaceous hyperplasia, 5 sebaceoma) and 25 controls (16 BCC, 9 SCC). Tissue microarrays were stained with AR, STAT6, and PMS2. Positive staining was defined as >10% nuclear staining for AR and >10% cytoplasmic staining for STAT6. PMS2 showed two reproducible patterns: cytoplasmic with nuclear staining and purely cytoplasmic staining, each requiring >10% of tumor cells for positivity. Two blinded dermatopathologists independently scored all cases; discrepancies were resolved with a third dermatopathologist. Sensitivity/specificity: AR (90.0%/62.0%), STAT6 (91.3%/40.0%), PMS2 nuclear+/cytoplasmic (68.7%/86.0%), PMS2 cytoplasmic only (8.0%/100%). Combining stains improved specificity: AR+STAT6 (83.3%/70.0%), AR+PMS2 nuclear+/cytoplasmic (66.0%/96.0%). Subgroup analysis showed that most false positives for AR and STAT6 arose from BCC with adnexal differentiation, whereas PMS2 nuclear+/cytoplasmic staining was rare in BCC and SCC, and PMS2 cytoplasmic only staining was absent in all controls. AR with STAT6 provided the best balance of sensitivity and specificity, while AR with PMS2 nuclear+/cytoplasmic maximized specificity. These combinations may aid in diagnosing sebaceous neoplasms in challenging cases and have potential clinical implications for identifying patients with Muir-Torre syndrome.