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.

Evaluation of Immunohistochemical Markers, CK17 and SOX2, as Adjuncts to p53 for the Diagnosis of Differentiated Vulvar Intraepithelial Neoplasia (dVIN)

“…Therefore, increased p53-expression may be observed in non-dysplastic lesions as well [45]. Moreover, a proportion of dVIN (26% in our series), and the recently recognized VSCC precursor, de-VIL, show wild-type p53-expression [2,10,23,24]. In addition to p53 and p16, the proliferation marker MIB1 is commonly used to aid the diagnosis of dVIN.…”

“…Studies report that dVIN can progress rapidly to VSCC [5,6]; therefore, lesions diagnosed on histology as dVIN are surgically excised [7,8]. However, histological diagnosis of dVIN can be difficult even for experienced pathologists [2], and may suffer from suboptimal reproducibility [9,10].…”

The European Society of Gynaecological Oncology (ESGO), the International Society for the Study of Vulvovaginal Disease (ISSVD), the European College for the Study of Vulval Disease (ECSVD) and the European Federation for Colposcopy (EFC) consensus statements on pre-invasive vulvar lesions

“…Accurate histological diagnosis is crucial for appropriate treatment; histological assessment of vulvar intraepithelial lesions requires pathologists dealing with high-volume vulvar biopsies. Inter-observer agreement was demonstrated low for VHSIL70 and it is even worse for dVIN diagnosis71 72 where associated dermatoses complicate the histological pattern 73…”

Early Diagnostics of Vulvar Intraepithelial Neoplasia

“…These lesions arise out of lichenoid dermatitis and lack the basal atypia required for dVIN. Histological interpretation of dVINs and distinguishing them from VAMs and even HSILs remain challenging tasks with suboptimal interobserver agreement [ 37 ].…”