Multinucleated atypia of the vulva. Report of a distinct entity not associated with human papillomavirus

Abstract

The vulvar mucosa often demonstrates epithelial nuclear atypia in association with reactive and inflammatory conditions. These nuclear changes are usually mild and can be readily distinguished from vulvar intraepithelial neoplasia (VIN) and human papillomavirus (HPV)-related lesions. In a recent survey of vulvar biopsies in reproductive-aged women, we identified 12 cases of an unusual pattern of atypia associated with multinucleated epithelial cells but lacking the usual stigmata of reactive changes, condyloma, or VIN. The average age of the patients with multinucleated atypia of the vulva (MAV) was 37 years. The multinucleated cells were commonly in the lower to middle epithelial layers and contained between two and 10 nuclei, often with prominent nucleoli. In contrast to condyloma and VIN, there was no surface atypia, and the multinucleated cells lacked hyperchromasia, irregularity, or variation in nuclear size. No significant inflammation or identifiable infectious process was present, and none of the patients had received any topical treatment other than mild corticosteroids. Two of the patients had a history of VIN at a noncontiguous site. None of the 12 cases contained HPV DNA by either in situ hybridization or polymerase chain reaction (PCR) restriction fragment length polymorphism (RFLP) analysis. This is in contrast to 49 of 65 women with VIN and 21 of 26 with condyloma who had HPV demonstrable by the PCR method (p < 0.00001). Immunoperoxidase stains for herpes types I and II were also negative in all the cases. Thus, MAV appears to be a distinct entity occurring in relatively young women; when it is not associated with condyloma or VIN, MAV is not related to HPV. As the morphologic features may overlap with both condyloma and VIN, it is important that MAV not be confused with these lesions or vice versa. It is not known whether MAV is a risk factor for VIN, represents an exaggerated reactive response, or is an entity with a distinct origin.