Genital basal cell carcinoma, a different pathogenesis from sun-exposed basal cell carcinoma? A case-control study of 30 cases.

Background: Genital basal cell carcinoma (BCC) accounts for <1% of all BCCs. We aimed to elucidate the pathogenesis of genital BCC.

Methods: We retrospectively evaluated cases of pathologically diagnosed genital BCC between 1990 and 2016 in an Asian tertiary referral center. The control group was composed of consecutive cases, from 2016, of BCCs occurring in sun-exposed areas. Presence of human papillomavirus (HPV) was evaluated by polymerase chain reaction (PCR). Immunohistochemical p16 and p53 staining was performed and analyzed.

Results: We found 33 genital BCCs (33/1837, 1.8%) over 26 years. The mean follow-up duration was 30.0 ± 33.2 months. Genital BCCs had a larger size (14.05 vs 8.92 mm, P = 0.014), more common presence of ulcers (61.3% vs 32.0%, P = 0.035), shorter epidermal p53 clone (0.33 vs 1.20 mm, P = 0.007), and high p53 expression levels. Most cases (29/30, 96.7%) showed negative or faint spotty p16 staining. Patient age, tumor depth, presence of pigment, or histology subtype did not differ significantly. Thirty genital BCCs were negative for HPV.

Conclusions: HPV infection is mostly likely not involved in genital BCC pathogenesis. A greater level of p53 expression in genital BCCs implicates pathways other than ultraviolet (UV)-specific p53 mutations in their pathogenesis.