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Histological interpretation of differentiated vulvar intraepithelial neoplasia (dVIN) remains challenging-observations from a bi-national ring-study.

ABSTRACT: Differentiated vulvar intraepithelial neoplasia (dVIN) is a premalignant lesion that is known to progress rapidly to invasive carcinoma. 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 > 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 (ĸ)-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 (ĸ = 0.42), and pair-wise agreements ranged from slight (ĸ = 0.10) to substantial (ĸ = 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 × 100, and altered cellular alignment. p53-IHC patterns showed substantial concordance (ĸ = 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.

SUBMITTER: Dasgupta S

PROVIDER: S-EPMC8364542 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:OBJECTIVE:The aim of the study was to describe the demographic, clinical, and histopathologic features of differentiated vulvar intraepithelial neoplasia (dVIN) and vulvar aberrant maturation (VAM). METHODS:Specimens from 2010 to 2020 reported as dVIN or VAM were reviewed. Clinical data included age, rurality, symptoms, and evidence of lichen sclerosus (LS). Histopathologic data included epithelial thickness, keratinization, architectural and dyskeratotic features, stroma, p16, and p53. Differentiated vulvar intraepithelial neoplasia and VAM were distinguished by assessment of basal nuclear chromatin, enlargement, pleomorphism, and mitoses. RESULTS:One hundred twenty women with a median age of 71 years had 179 examples of dVIN and VAM. Squamous cell carcinoma was concurrent in 66% and associated with rurality. Ten percent were asymptomatic, and all but 3 had evidence of LS. Differentiated vulvar intraepithelial neoplasia showed a range of thickness, architecture, and dyskeratosis; its unifying !feature was basal atypia. Differentiated vulvar intraepithelial neoplasia displayed hyperchromasia in 83% and easily observed mitoses in 70%. Nonkeratinizing morphology, subcategorized into basaloid and intermediate, occurred in 24% of women with dVIN. Traditional dVIN represented 62% of keratinizing cases; the remainder were atrophic (13%), hypertrophic (13%), acantholytic (8%), or subtle (5%). Vulvar aberrant maturation had abnormal stratum corneum, acanthosis, premature maturation, and enlarged vesicular nuclei. Null p53 helped distinguish dVIN from VAM and dermatoses. CONCLUSIONS:The morphology of dVIN encompasses nonkeratinizing and keratinizing types, the latter subdivided into traditional, acantholytic, atrophic, hypertrophic, and subtle. Diagnosis relies on basal atypia with supportive p16 and p53. Atypia exists on a biologic spectrum with mild abnormalities of VAM and reactive change. Identification of dVIN and VAM requires collaboration between clinicians and pathologists experienced in vulvar disorders.

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Histological interpretation of differentiated vulvar intraepithelial neoplasia (dVIN) remains challenging-observations from a bi-national ring-study.

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