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Abstract

Basal cell nevus syndrome (BCNS) is a rare autosomal dominant genodermatosis caused by Hedgehog pathway gene mutations, most commonly PTCH1. BCNS is characterized by multiple basal cell carcinomas (BCCs) beginning in adolescence. Treatment options include vismodegib systemic therapy and topical therapies such as photodynamic therapy (PDT). Although PDT and visomodegib are known to have immunomodulatory capabilities, their effects on the immune microenvironment of BCNS-associated BCCs have not previously been reported. A search of the pathology laboratory information system and electronic medical records of a single academic hospital yielded 14 BCC biopsy or resection specimens from 6 BCNS patients (female, n = 4) with a mean age of 39 years at first specimen collection (range: 14-64 years). Prior treatments included visomodegib (n=4), PDT (n=2), or no treatment (n=8). Immunohistochemical stains for CD3, CD4, CD8, FOXP3, and CD68 were performed on each case. Positive cells in the intratumoral and peritumoral compartments were quantified in three high-powered fields of high cell density per case by two independent reviewers. PDT-treated tumors were associated with significantly higher mean CD3+, CD8+, FOXP3+, and CD68+ cell counts within peritumoral stroma compared to tumors with no prior treatment (one-way ANOVA, p<0.05). There were no significant differences in intratumoral cell counts between groups. These findings suggest PDT enhances peritumoral immune cell recruitment in BCNS-associated BCCs, while vismodegib-treated tumors did not show significant changes in peritumoral immune cell composition compared to untreated tumors. These results highlight differential immunomodulatory effects of these therapies in BCNS.