HPV-negative Vulvar Intraepithelial Neoplasia (VIN) With Basaloid Histologic Pattern: An Unrecognized Variant of Simplex (Differentiated) VINOrdi, Jaume MD*; Alejo, Maria MD†; Fusté, Victòria MD*; Lloveras, Belen MD‡; del Pino, Marta MD§; Alonso, Immaculada MD§; Torné, Aureli MD§The American Journal of Surgical Pathology: November 2009 - Volume 33 - Issue 11 - p 1659-1665 doi: 10.1097/PAS.0b013e3181b40081 Original Articles Buy SDC Abstract Author InformationAuthors Article MetricsMetrics Vulvar intraepithelial neoplasia (VIN) is classified into 2 clinicopathologic subtypes, classic, related to human papillomavirus (HPV) infection and affecting relatively young women, and simplex (differentiated), negative for HPV and affecting elderly women. Histologically, classic VIN may be basaloid and characterized by a replacement of the whole epidermis by a homogeneous population of small, “undifferentiated” keratinocytes, which are diffusely positive for p16INK4a and negative for p53. Simplex VIN is characterized by atypia of the basal layer with high degree of cellular differentiation and shows negative staining for p16INK4a and frequent positivity for p53. Simplex VIN is frequently associated with squamous cell hyperplasia and lichen sclerosus. From a series of 110 invasive squamous cell carcinomas of the vulva negative for HPV by highly sensitive polymerase chain reaction, 51 had VIN lesions located at least 1 cm away from the tumor. In 4 (7.8%) cases, the VIN had basaloid histologic features. All cases showed obvious architectural disorganization with a homogeneous population of basaloid, undifferentiated keratinocytes with scanty cytoplasm replacing the whole epidermis. Immunohistochemically, all cases were negative for p16INK4a and strongly positive for p53 with suprabasilar extension of positive cells. All patients were postmenopausal (median age 61.0 y; range, 45-76). Squamous cell hyperplasia was identified in 1 case and lichen sclerosus in 1 case. The invasive squamous cell carcinoma was of keratinizing type in 3 cases and basaloid in 1 case. In conclusion, simplex, HPV-negative VIN may occasionally have basaloid morphology. Immunostaining for p16INK4a and p53 protein may be helpful in the identification of these lesions and the differential diagnosis with classic, HPV-positive basaloid VIN. Departments of *Pathology §Obstetrics and Gynecology, Hospital Clínic-IDIBAPS, University of Barcelona †Department of Pathology, Hospital de Vic, Barcelona ‡Unit of Infections and Cancer, Institut Català d'Oncologia-IDIBELL, CIBERESP, L'Hospitalet, Spain Correspondence: Jaume Ordi, MD, Department of Pathology, Hospital Clínic, C/Villarroel 170, 08036-Barcelona, Spain (e-mail: firstname.lastname@example.org). © 2009 Lippincott Williams & Wilkins, Inc.