Genomic and clinical characterization of anogenital basal cell carcinoma: A retrospective and prospective cohort study.

Abstract

Anogenital basal cell carcinoma (BCC) is a rare and poorly understood subtype occurring in sun-protected areas. To investigate the clinicopathological and genomic characteristics of anogenital BCC. Patients with anogenital BCC diagnosed between 2006 and 2024 were included from a nationwide retrospective-prospective cohort. Clinicopathological features were assessed, and whole-genome or whole-exome sequencing was performed for genomic analysis. Among 50 patients (40 female, 10 male), the vulva was the most frequently affected site in women, whereas the perianal region prevailed in men. 3 patients had prior pelvic radiotherapy. Nodular (n = 23, 46%) and infiltrative subtypes (n = 22, 45%) predominated, with 18% of vulvar BCCs developing on lichen sclerosus. Most cases (n = 42, 84%) underwent surgical removal alone; 3 (6%) received neoadjuvant hedgehog inhibitors. Recurrence occurred in 15% of treated cases (median follow-up: 7 years). Genomic analyses (n = 12) revealed low tumor mutational burden (3.4 mutations/Mb), no UV mutational signatures, frequent PTCH1 mutations (75%), and activation of the sonic hedgehog pathway. Small sample size and retrospective design. Anogenital BCCs exhibit distinct clinicopathological and genomic features, including higher recurrence rates, UV-independence, and sonic hedgehog pathway activation, requiring adapted diagnostic and treatment strategies.