Immunohistochemical Predictors in Head and Neck Mucosal Melanoma

Mucosal melanoma is a rare disease with a poor prognosis, and its clinical signs and symptoms are nonspecific. This study aims to identify histopathological features and immunohistochemical markers of head and neck mucosal melanoma that characterize the tumor immunophenotype and are associated with patient survival.

The study analysed head and neck mucosal melanoma diagnosed at Helsinki University hospital between January 1, 2011, and June 8, 2023. Samples were obtained from the Helsinki Biobank in Finland. New slides were prepared and stained for hematoxylin and eosin (H&E), CD3, CD4, CD8, Granzyme B (GrzB), CD68, CD117, p16INK4a, p53, SOX10 and PRAME.

The study included 23 patients, 10 men and 13 women, aged 60-92 years (mean 75 years). The tumors were predominantly sinonasal. Ulceration was present in 15 cases, also 15 cases were amelanotic. Immunohistochemical staining SOX10 was positive in all tumors. PRAME was strongly positive in majority (20 cases, 87%). Strong p16 positivity was observed in 13 cases (57%), with a longer median survival compared to cases with weakened p16 expression (32.8 vs 13.8 months, p = 0.176). The median survival was also longer in the cases with high score of tumor infiltrating CD3-, CD8- and CD68-positive immune cells, though not statistically significant.

Immunohistochemical markers routinely applied in cutaneous melanoma (SOX-10 and PRAME) are also expressed in head and neck mucosal melanoma. Tumour-infiltrating immune cells showed trend toward better survival, as has been previously found out in cutaneous melanoma. Strong p16 positivity may be an independent predictor of favorable prognosis in head and neck mucosal melanoma, irrespective of disease stage. Larger multicenter studies are warranted to validate these findings in this rare disease.