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Accurate histological diagnosis is therefore crucial to allow appropriate treatment. To identify reliable diagnostic features, we evaluated the inter-observer agreement in the histological assessment of dVIN, among a bi-national, multi-institutional group of pathologists. Two investigators from Erasmus MC selected 36 hematoxylin-eosin-stained glass slides of dVIN and no-dysplasia, and prepared a list of 15 histological features of dVIN. Nine participating pathologists (i) diagnosed each slide as dVIN or no-dysplasia, (ii) indicated which features they used for the diagnosis, and (iii) rated these features in terms of their diagnostic usefulness. Diagnoses rendered by &gt; 50% participants were taken as the consensus (gold standard). p53-immunohistochemistry (IHC) was performed for all cases, and the expression patterns were correlated with the consensus diagnoses. Kappa (<jats:italic>\u0138<\/jats:italic>)-statistics were computed to measure inter-observer agreements, and concordance of the p53-IHC patterns with the consensus diagnoses. For the diagnosis of dVIN, overall agreement was moderate (<jats:italic>\u0138<\/jats:italic>= 0.42), and pair-wise agreements ranged from slight (<jats:italic>\u0138<\/jats:italic>= 0.10) to substantial (<jats:italic>\u0138<\/jats:italic>= 0.73). Based on the levels of agreement and ratings of usefulness, the most helpful diagnostic features were parakeratosis, cobblestone appearance, chromatin abnormality, angulated nuclei, atypia discernable under \u00d7 100, and altered cellular alignment. p53-IHC patterns showed substantial concordance (<jats:italic>\u0138<\/jats:italic>= 0.67) with the consensus diagnoses. Histological interpretation of dVIN remains challenging with suboptimal inter-observer agreement. We identified the histological features that may facilitate the diagnosis of dVIN. For cases with a histological suspicion of dVIN, consensus-based pathological evaluation may improve the reliability of the diagnosis.<\/jats:p>","DOI":"10.1007\/s00428-021-03070-0","type":"journal-article","created":{"date-parts":[[2021,3,8]],"date-time":"2021-03-08T04:16:58Z","timestamp":1615177018000},"page":"305-315","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Histological interpretation of differentiated vulvar intraepithelial neoplasia (dVIN) remains challenging\u2014observations from a bi-national ring-study"],"prefix":"10.1007","volume":"479","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1804-5015","authenticated-orcid":false,"given":"Shatavisha","family":"Dasgupta","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elf","family":"de Jonge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4498-928X","authenticated-orcid":false,"given":"Mieke R.","family":"Van Bockstal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luthy S. 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