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.

FIGURE 1

A, Vulvar aberrant maturation—white plaques with a rough surface over posterior fourchette and perineum, background of LS-associated architectural change. B, Parakeratosis, hypergranulosis, acanthosis with clubbed rete ridges, premature maturation, prominent intercellular prickles, and vesicular basal nuclei, H&E ×100. C, Uniform vesicular nuclei with intranuclear vacuoles and occasional prominent nucleoli, H&E ×400. D, p16 is nonblock positive with focal variable cytoplasmic and nuclear staining, ×200. E, p53 is wild type, ×200. F, Two years later, excision of the white plaque shows traditional keratinizing dVIN with PK, anastomosing rete ridges, premature maturation, and basal atypia seen as hyperchromasia, pleomorphism, enlargement, and an abnormal mitosis, H&E ×200.

FIGURE 2

A, Differentiated vulvar intraepithelial neoplasia—glazed red macule at left clitoral frenulum on a background of LS. B, Basaloid dVIN with erosion, full-thickness atypical nuclei, multiple mitoses, and moderate lymphoplasmacytic infiltrate, H&E ×200. C, p16 is negative, ×200. D, p53 is overexpressed at basal and suprabasal layers, ×200.

FIGURE 3

A, Differentiated vulvar intraepithelial neoplasia—large glazed red patch over bilateral labia minora and right interlabial fold. B, Subtle keratinizing dVIN with PK, flat acanthosis, and mildly hyperchromatic enlarged nuclei extending halfway up the epithelium, H&E ×200. C, Junction between dVIN and thinner nonneoplastic epithelium, H&E ×200. D, p16 is negative, ×200. E, Basal and suprabasal overexpressed p53 in dVIN contrasts with wild-type pattern in adjacent epithelium, ×200.

FIGURE 4

A, Squamous cell carcinoma and dVIN—central tumor surrounded by a white heterogeneous plaque. B, Hypertrophic keratinizing dVIN with thick PK and wide elongated rete ridges, H&E ×100. C, Vesicular nuclei with marked enlargement and multiple nucleoli, H&E ×400. D, p16 is negative ×100. E, p53 is aberrant negative, ×100.

FIGURE 5

A, Exophytic red HPV-related SCC on a background of uncontrolled LS. B, Excision from the contralateral side with traditional keratinizing dVIN seen as PK, spiky rete ridges, and spindle-shaped hyperchromatic, pleomorphic, enlarged nuclei, H&E ×200. C, p16 is block positive, ×100. D, p53 is aberrant negative suggesting dual carcinogenic etiology, ×100.

FIGURE 6

A, Atrophic keratinizing dVIN with LS-like appearance—thin epithelium, absent rete ridges, basal atypia comprising half the epithelium, and band of edematous and hyalinized collagen overlying moderate lymphocytic infiltrate, H&E ×200. B, p16 is negative, ×200. C, p53 is aberrant negative, ×400.

FIGURE 7

A, Intermediate type of nonkeratinizing dVIN—amphiphilic appearance with PK, uniform acanthosis, and atypical nuclei with cellular maturation occurring at the superficial 30% of epithelium, H&E ×200. B, p16 is negative, ×200. C, p53 is overexpressed at basal and suprabasal layers, ×200.

FIGURE 8

Algorithm for the morphologic subsets of dVIN.

FIGURE 9

A, Squamous cell carcinoma and dVIN—red plaque at right clitoral frenulum on a background of uncontrolled LS. B, Acantholytic type of keratinizing dVIN—PK, normal thickness, marked intercellular prickles, intercellular and intracellular vacuoles with fluid-filled spaces, and sclerosis, H&E ×200. C, p16 is negative, ×200. D, p53 is overexpressed at basal and suprabasal layers, ×200.