Diagnostic Criteria for Differentiated Vulvar Intraepithelial Neoplasia and Vulvar Aberrant Maturation

Abstract

Objective The aim of the study was to describe the features required for diagnosis of differentiated vulvar intraepithelial neoplasia (dVIN) and vulvar aberrant maturation (VAM). Materials and Methods The International Society of the Study of Vulvovaginal Diseases tasked the difficult pathologic diagnoses committee to develop consensus recommendations for clinicopathologic diagnosis of vulvar lichen planus, lichen sclerosus, and dVIN. The dVIN subgroup reviewed the literature and formulated diagnostic criteria that were reviewed by the committee and then approved by the International Society of the Study of Vulvovaginal Diseases membership. Results Differentiated vulvar intraepithelial neoplasia is the immediate precursor of human papillomavirus (HPV)–independent vulvar squamous cell carcinoma and shows a spectrum of clinical and microscopic appearances, some overlapping with HPV-related neoplasia. The histopathologic definition of dVIN is basal atypia combined with negative or nonblock-positive p16 and basal overexpressed, aberrant negative, or wild-type p53. The most common pattern of dVIN is keratinizing with acanthosis, aberrant rete ridge pattern, and premature maturation. The morphologic spectrum of keratinizing dVIN includes hypertrophic, atrophic, acantholytic, and subtle forms. A few dVIN cases are nonkeratinizing, with basaloid cells replacing more than 60% of epithelium. Vulvar aberrant maturation is an umbrella term for lesions with aberrant maturation that arise out of lichenoid dermatitis and lack the basal atypia required for dVIN. Conclusions Evaluation of women at risk for dVIN and VAM requires a collaborative approach by clinicians and pathologists experienced in vulvar disorders. Close surveillance of women with lichen sclerosus and use of these recommendations may assist in prevention of HPV-independent squamous cell carcinoma through detection and treatment of dVIN and VAM.

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.…”

“…The spectrum of histological features of dVIN can overlap with that of non-dysplastic lesions, and occasionally, with that of HPV-related HSILs as well [ 40 , 41 ]. Therefore, to improve diagnostic accuracy, an IHC panel comprising p16 and p53 is being recommended for lesions with a histological suspicion of dVIN [ 2 , 4 , 17 , 39 ]. Block-type p16-expression is a reliable surrogate of high-risk HPV-infection, and helps discriminate HSIL from dVIN [ 40 , 41 ].…”

“…Vulvar squamous cell carcinoma (VSCC) is classified etiologically into human papilloma virus (HPV)-related, and HPV-independent subtypes [ 1 , 2 , 3 , 4 ]. HPV-independent VSCC is the more prevalent subtype [ 3 ] that typically arises in the setting of chronic dermatoses.…”

“…HPV-independent VSCC is the more prevalent subtype [ 3 ] that typically arises in the setting of chronic dermatoses. Differentiated vulvar intraepithelial neoplasia (dVIN) is the most well-characterized precursor lesion of HPV-independent VSCC [ 1 , 2 , 3 , 4 ]. Studies report that dVIN can progress rapidly to VSCC [ 5 , 6 ]; therefore, lesions diagnosed on histology as dVIN are surgically excised [ 7 , 8 ].…”

Nuclear factor IB is downregulated in vulvar squamous cell carcinoma (VSCC): Unravelling differentially expressed genes in VSCC through gene expression dataset analysis

“…p53-wild-type patterns include scattered heterogeneous basal and/or para-basal expression, and scattered mid-epithelial expression with basal sparing. The latter p53-wild-type pattern is associated with HPV-related lesions ( 10 , 22 ).…”