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

Shatavisha Dasgupta*, Elf de Jonge, Mieke R. Van Bockstal, Luthy S.M. Wong-Alcala, Suzanne Wilhelmus, Lex A.C.F. Makkus, Katrien Schelfout, Koen K. Van de Vijver, Sander Smits, Etienne Marbaix, Senada Koljenović, Folkert J. van Kemenade, Patricia C. Ewing-Graham

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

14 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)305-315
Number of pages11
JournalVirchows Archiv
Issue number2
Publication statusPublished - Aug 2021

Bibliographical note

Funding Information:
The authors are grateful to Mr. Hongchao Qi, Statistical Consultant, Department of Bio-statistics, Erasmus MC, for his guidance on the data analyses, and to Dr. Thierry P.P. van den Bosch, Dr. Remko Hersmus, and Ms. Linda Coelers, from the Department of Pathology, Erasmus MC, for their excellent technical assistance.

Publisher Copyright:
© 2021, The Author(s).


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