Department of Pathology, Erasmus MC, University Medical Centre, Postbus 2040, Be-building, 3000CA, Rotterdam, The Netherlands.
Department of Pathology, Groene Hart Ziekenhuis, Gouda, The Netherlands.
Virchows Arch. 2021 Aug;479(2):305-315. doi: 10.1007/s00428-021-03070-0. Epub 2021 Mar 8.
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.
分化型外阴上皮内瘤变（dVIN）是一种癌前病变，已知其会迅速进展为浸润性癌。因此，准确的组织学诊断对于提供适当的治疗至关重要。为了确定可靠的诊断特征，我们评估了一个跨国、多机构的病理学家小组在 dVIN 的组织学评估中的观察者间一致性。来自伊拉斯谟医学中心的两名研究人员选择了 36 张 dVIN 和无发育不良的苏木精-伊红染色玻片，并列出了 15 项 dVIN 的组织学特征。9 名参与的病理学家（i）将每张幻灯片诊断为 dVIN 或无发育不良，（ii）指出他们用于诊断的特征，以及（iii）根据其诊断有用性对这些特征进行评分。> 50%的参与者做出的诊断被视为共识（金标准）。对所有病例进行 p53-免疫组化（IHC）检测，并将表达模式与共识诊断相关联。计算 κ 统计量以测量观察者间的一致性，并评估 p53-IHC 模式与共识诊断的一致性。对于 dVIN 的诊断，总体一致性为中度（κ=0.42），并且两两一致性从轻微（κ=0.10）到显著（κ=0.73）不等。基于一致性水平和有用性评分，最有帮助的诊断特征是角化不良、鹅卵石样外观、染色质异常、角状核、在×100 下可识别的异型性和细胞排列改变。p53-IHC 模式与共识诊断具有显著的一致性（κ=0.67）。dVIN 的组织学解释仍然具有挑战性，观察者间一致性不佳。我们确定了可能有助于 dVIN 诊断的组织学特征。对于具有组织学怀疑为 dVIN 的病例，基于共识的病理评估可能会提高诊断的可靠性。
