TRPS1 expression in cutaneous and mucosal melanoma: a retrospective study of 64 cases.

TRPS1 is a sensitive immunohistochemical marker for breast carcinoma, but its expression in melanoma remains incompletely characterized, and mucosal melanoma has been underrepresented in prior studies. We evaluated TRPS1 expression in a mucosal-enriched cohort of 64 melanomas (54 primary and 10 metastatic) and 10 benign melanocytic nevi using whole-tissue sections. TRPS1 expression was scored semi-quantitatively, and a cutoff-sensitivity analysis was performed. In this mucosal-enriched cohort (51.6% mucosal, predominantly acral cutaneous), moderate-to-high TRPS1 expression (score ≥ 3) was observed in 10 of 64 melanomas (15.6%; 95% CI, 8.7-26.4), including 7 of 33 mucosal melanomas (21.2%; 95% CI, 10.7-37.8) and 3 of 21 cutaneous melanomas (14.3%; 95% CI, 5.0-34.6). None of the 10 metastatic melanomas showed moderate-to-high expression (0%; 95% CI, 0-27.8). Among the TRPS1-positive cases, SOX10 was positive in all 8 cases tested, and S100, Melan-A, and HMB45 were positive in 7 of 8, 7 of 8, and 9 of 10 cases tested, respectively. The positivity rate decreased progressively across cutoffs, without a sharp threshold effect. These findings indicate that TRPS1 positivity does not exclude melanoma, and that TRPS1 negativity should not exclude melanoma either. A melanocytic panel combining a sensitive nuclear marker (SOX10 or S100) with a lineage-specific cytoplasmic marker (Melan-A or HMB45) should be performed for any cutaneous or mucosal tumor in which melanoma is in the differential diagnosis, regardless of TRPS1 status.