Hypertrophic Lichen Sclerosus: A Form of "Atypical" Lichen Sclerosus in the Pathway to HPV-Independent Squamous Cell Carcinoma of the Vulva.

Hypertrophic lichen sclerosus (HLS) is poorly characterized. A recent study described an atypical form of LS (p53 wild type) with a CK17/D2-40 immunohistochemical profile intermediate between classic LS and differentiated vulvar intraepithelial neoplasia (dVIN). Our study aims to characterize HLS through IHC and molecular profiling to determine if it is a classic or atypical LS lesion. We reviewed HLS diagnosed in 12 biopsies (2014 to 2025) and 5 resections for vulvar squamous cell carcinoma (vSCC) (1998 to 2015) from our institution (mean patient age 59; range: 37 to 97). We defined HLS by nonexophytic acanthosis, hyperkeratosis +/- parakeratosis, granular layer retention, irregular dermal-epidermal junction, lack of severe basal layer atypia, homogenization of the superficial dermis, and +/- lichenoid inflammatory infiltrate. In the 5 resections, CK17 expression was suprabasal in 4 (80%) and superficial in 1 (20%) of HLS adjacent to vSCC. D2-40 intensity was moderate in all 5 (100%). All 5 vSCC were p16-/p53 aberrant with intense D2-40 expression and showed diffuse CK17 in 4 (80%) and suprabasal staining in 1 (20%). All 12 HLS biopsies were p16-; 7 (58%) were p53 wild type and 5 (42%) were aberrant. Seven (58%) showed CK17 suprabasal staining; 5 (42%) were diffuse. D2-40 intensity ranged from absent (1/12; 8%) to faint (3/12; 25%) to moderate (3/12; 25%) to intense (5/12; 42%). Frequently altered genes were SDHA (3/6; 50%) and TP53 (2/6; 33%). HLS shows neither the classic morphology of LS nor dVIN but can be p53 aberrant/mutant. Because of its CK17/D2-40 immunophenotype, it should be considered as atypical LS.