Background: Differentiated vulvar intraepithelial neoplasia (VIN) is presumed to be the precursor of invasive squamous cell carcinoma (SCC) of the vulva. It is commonly assumed that differentiated VIN is related to lichen sclerosus (LS). However, evidence for this is limited to a small number of studies describing epithelial alterations adjacent to vulvar SCC. Aim: To study the histology and human papillomavirus (HPV) status in patients with a history of both LS and VIN without coexistent SCC. Methods: Original biopsy specimens and surgical specimens of patients retrieved from the pathology files were revised for the presence of LS, VIN and (early) invasive SCC, specifically focused on the two different types of VIN: differentiated and undifferentiated. Thereafter, VIN lesions were tested for the presence of HPV DNA. Results: Twenty-seven patients fulfilled the criteria for LS and VIN without SCC. In all 27 patients, LS was found to be related to undifferentiated VIN. Grading yielded the following results: VIN 1 (n = 10), VIN 2 (n = 11) and VIN 3 (n = 6). Additionally, VIN lesions from 26 patients could be tested for the presence of HPV DNA. HPV DNA, predominantly type 16, was present in 8 (31%) of them. Seven of these eight patients had VIN 2 or 3. During follow-up, three patients progressed to (early) invasive carcinoma. In two of these patients, differentiated VIN was observed overlying early invasive SCC. Conclusions: VIN related to LS without coexisting SCC is likely to be undifferentiated, in contrast to what was previously thought. HPV DNA was demonstrated in 31% of the lesions, and was strongly related to high-grade VIN.

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Seters, van, M, ten Kate, F.J.W, van Beurden, M, Verheijen, R.H.M, Meijer, C.J.L.M, Burger, M.P.M, & Helmerhorst, T.J.M. (2007). In the absence of (early) invasive carcinoma, vulvar intraepithelial neoplasia associated with lichen sclerosus is mainly of undifferentiated type: New insights in histology and aetiology. Journal of Clinical Pathology: an international peer-reviewed journal for health professionals and researchers in clinical pathology, 60(5), 504–509. doi:10.1136/jcp.2005.031989