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.

Cervico-vaginal (CV) localization of extra-mammary Paget’s disease (EMPD) of the vulva is extremely rare. In order to investigate the incidence risk and the pathognomonic clinical and pathological features of this condition, a retrospective analysis was conducted including 94 women treated for vulvar EMPD at the European Institute of Oncology, Milan, Italy, from October 1997 to May 2020. Overall nine patients developed CV involvement from EMPD, with a cumulative incidence of 2.5% (95% CI: 0.5–8.0%) at 5 years, 6.5% (95% CI: 1.9–15.1%) at 10 years and 14.0% (95% CI: 4.8–27.8%) at 15 years, respectively. All cases except one were firstly detected by abnormal glandular cytology. None reported vaginal bleeding or other suspicious symptoms. The colposcopic findings were heterogeneous and could sometimes be misdiagnosed. Cervical and/or vaginal biopsies were always performed for histopathological diagnosis by identification of Paget cells in the epithelium or stroma. Most patients developed invasive EMPD (5/9) of the cervix and/or vagina and underwent hysterectomy with partial or total colpectomy. CV involvement from EMPD should not be underestimated in women with a long-standing history of vulvar Paget’s disease. Liquid-based cytology with immunocytochemistry represents a valuable tool for early diagnosis and should be routinely performed during the required lifelong follow-up.