Interobserver variability and the effect of education in the histopathological diagnosis of differentiated vulvar intraepithelial neoplasia

Abstract

No published data concerning intraobserver and interobserver variability in the histopathological diagnosis of differentiated vulvar intraepithelial neoplasia (DVIN) are available, although it is widely accepted to be a subtle and difficult histopathological diagnosis. In this study, the reproducibility of the histopathological diagnosis of DVIN is evaluated. Furthermore, we investigated the possible improvement of the reproducibility after providing guidelines with histological characteristics and tried to identify histological characteristics that are most important in the recognition of DVIN. A total number of 34 hematoxylin and eosin-stained slides were included in this study and were analyzed by six pathologists each with a different level of education. Slides were reviewed before and after studying a guideline with histological characteristics of DVIN. Kappa statistics were used to compare the interobserver variability. Pathologists with a substantial agreement were asked to rank items by usefulness in the recognition of DVIN. The interobserver agreement during the first session varied between 0.08 and 0.54, which slightly increased during the second session toward an agreement between À 0.01 and 0.75. Pathologists specialized in gynecopathology reached a substantial agreement (kappa 0.75). The top five of criteria indicated to be the most useful in the diagnosis of DVIN included: atypical mitosis in the basal layer, basal cellular atypia, dyskeratosis, prominent nucleoli and elongation and anastomosis of rete ridges. In conclusion, the histopathological diagnosis of DVIN is difficult, which is expressed by low interobserver agreement. Only in experienced pathologists with training in gynecopathology, kappa values reached a substantial agreement after providing strict guidelines. Therefore, it should be considered that specimens with an unclear diagnosis and/or clinical suspicion for DVIN should be revised by a pathologist specialized in gynecopathology. When adhering to suggested criteria the diagnosis of DVIN can be made easier.

Vulvar Lichen Sclerosus and Neoplastic Transformation

“…Two possible explanations for the low incidence of dVINs are (1) that it is a transient intraepithelial lesion that rapidly progresses to invasive carcinoma or (2) that it is an underdiagnosed lesion because of its difficult clinical and histological recognition. 25 The latter is further supported by a recent study on the basis of a careful review of previously reported histological specimens, where dVIN was found in 42% of lesions previously diagnosed with VLS, which progressed to vulvar SCC. 26 Rapid progression to neoplasia or its underdiagnosis could also explain why dVIN accounts for only 2% to 10% of all reported VIN in the literature.…”

Expanding the Morphologic Spectrum of Differentiated VIN (dVIN) Through Detailed Mapping of Cases With p53 Loss

“…In a recent study on the reproducibility of diagnosis of dVIN, van den Einden et al 13 showed poor reproducibility/high interobserver variation. They identified 5 key histopathologic features of dVIN: (1) atypical basal mitotic figures, (2) basal atypia, (3) dyskeratosis, (4) prominent nucleoli, and (5) elongation and anastomosis of rete ridges.…”

“…Nonetheless, most cases of dVIN are diagnosed in association with invasive SCC, and isolated dVIN, without invasion, is uncommonly recognized by pathologists. 12,13 Mutations in TP53 are a hallmark of HPV-independent vulvar SCC. [14][15][16] It is now appreciated that mutant TP53 can show 1 of 2 patterns of expression on immunohistochemical (IHC) staining.…”

Vulvar intraepithelial neoplasia

“…Although the majority of vulvar SCC is not HPV associated, dVIN accounts for only 2e10% of all reported VIN. The possible explanations for dVIN's low prevalence are that it is a transient lesion that rapidly progresses to invasive carcinoma and/or it is an underdiagnosed and underreported lesion [17,18].…”