Clinicopathologic and Immunologic Features of Vulvar Lichen Sclerosus and Related Neoplasia: A Comparative Study of Precursor Lesions and VSCC in Premenopausal and Postmenopausal Patients.

Lichen sclerosus (LS) is a chronic inflammatory condition of the vulva. Although LS is thought to arise from autoimmune mechanisms, it is unclear whether disease drivers differ by menopausal status-an important distinction given its potential progression to differentiated vulvar intraepithelial neoplasia (dVIN) and vulvar squamous cell carcinoma (VSCC). We performed a retrospective review of 182 biopsy-proven LS cases (2020-2025), stratified by menopause status. In addition, we examined 27 VSCC cases for PD-L1 staining to assess immune modulation and potential therapeutic relevance. Premenopausal patients were diagnosed at a much younger age (37.8 vs. 67.5 yr, P <0.001) and experienced longer delays to diagnosis (3.9 vs. 1.5 yr, P <0.001). Their biopsies were less often reported with definitive LS terminology (40% vs. 75%, P <0.001), suggesting under-recognition in younger women. Comorbidities were more common in this group, especially autoimmune disease (46.7% vs. 10.9%, P <0.001), whereas postmenopausal patients more frequently had atrophic vaginitis (15.9%, P =0.02). Progression to dVIN or VSCC occurred more often in postmenopause (13.1% vs. 8.9%), though this was not statistically significant. PD-L1 expression was frequent in VSCC and precursor lesions (HSIL: 80%; dVIN: 81%) and less common in LS (50%), though these differences were not statistically significant. Expression patterns varied by lesion type, suggesting potential differences in the local immune microenvironment. Taken together, these findings support differences in clinical presentation and immune features of LS by menopausal status, warranting further investigation in larger cohorts.