title: HPV-negative vulvar intraepithelial neoplasia (VIN) with basaloid histologic pattern: an unrecognized variant of simplex (differentiated) VIN.
abstract: 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 p16(INK4a) 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 p16(INK4a) 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 p16(INK4a) 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 p16(INK4a) and p53 protein may be helpful in the identification of these lesions and the differential diagnosis with classic, HPV-positive basaloid VIN.
authors.affiliation: Department of Pathology, Hospital Clínic-IDIBAPS, University of Barcelona, Spain. jordi@clinic.ub.es
authors.forename: Jaume
authors.initials: J
authors.lastname: Ordi
authors.forename: Maria
authors.initials: M
authors.lastname: Alejo
authors.forename: Victòria
authors.initials: V
authors.lastname: Fusté
authors.forename: Belen
authors.initials: B
authors.lastname: Lloveras
authors.forename: Marta
authors.initials: M
authors.lastname: Del Pino
authors.forename: Immaculada
authors.initials: I
authors.lastname: Alonso
authors.forename: Aureli
authors.initials: A
authors.lastname: Torné
mesh_terms: D000368:Aged; D052685:Alphapapillomavirus / Q000235:genetics / Q000302:isolation & purification*; D002278:Carcinoma in Situ / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D004279:DNA, Viral / Q000032:analysis; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D006965:Hyperplasia; D018459:Lichen Sclerosus et Atrophicus / Q000150:complications / Q000473:pathology; D008875:Middle Aged; D030361:Papillomavirus Infections / Q000175:diagnosis; D012867:Skin / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014846:Vulvar Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000821:virology
chemical_list: D004279:DNA, Viral; D016159:Tumor Suppressor Protein p53