Epidermodysplasia verruciformis and cutaneous human papillomavirus DNA, but not genital human papillomavirus DNAs, are frequently detected in vulvar and vaginal melanoma.

Vulvovaginal melanomas are rare and their etiology is unknown. Genital mucosal human papillomavirus (HPV) 16 has been identified in both cutaneous and mucosal melanoma, suggesting that it might play a role in the pathogenesis or progression of melanoma. In this study, we investigated the prevalence of HPV DNA by using a broad spectrum of degenerate and type-specific primers for genital-mucosal, epidermodysplasia verruciformis-associated (EV), and cutaneous HPV types in 6 vulvar and 3 vaginal melanomas. The patients were mostly postmenopausal women (8/9), had a mean age of 67 years (range, 44-85 years), and had mucosal lentiginous (7) or nodular (2) melanomas. In the adjacent skin/mucosa, mucosal melanosis was found in 5, lichen sclerosus or a lichenoid mucositis in 4, and blue nevi in 2 women. With nested polymerase chain reaction techniques followed by direct sequencing, HPV DNA was identified in 6 of 9 (67%) melanomas; these were either cutaneous (HPV 3) (4/9) or epidermodysplasia verruciformis-associated types (HPV 38, Z95969, AJ00151) (4/9). Epidermodysplasia verruciformis-associated HPV (type 15) was found solely in 1/10 (10%) normal vulvar controls. Genital-mucosal HPV types were not detected either by degenerate nested polymerase chain reaction or type-specific probes for HPV 16. We propose that the above findings are not coincidental but may represent a molecular record of HPV involvement in pathogenesis or progression of melanoma, which is consistent with the strong but poorly defined association of cutaneous HPV types with nonmelanoma skin cancers. The theory that HPV may act as a cofactor in melanoma development deserves further clinical and experimental investigations.

Verrucous carcinoma of the endometrium: case history, pathologic findings, brief review of literature and discussion.

BACKGROUND: Verrucous carcinoma is a rare condition. A defined disease of the oral cavity, larynx, esophagus, skin, vulva, vagina and cervix. But a verrucous carcinoma arising from the endometrium without evidence of cervical malignancy or endometrial adenocarcinoma is extremely rare. CASE: A 67-year-old G2P2 menopausal patient that was referred for consultation 1 year after presenting with vaginal bleeding to her gynecologist who subsequently underwent several endometrial biopsies where the pathological findings were repetitively similar: papillary squamous proliferation, cytologically bland with low mitotic activity but extensive proliferation. A hysterectomy with bilateral salpingo-oophorectomy was performed. The final histologic examination revealed a squamous cell carcinoma of endometrium, verrucous and well differentiated, and there was no cervical invasion identified. CONCLUSION: This is a rare form of endometrial cancer with apparent favorable prognosis that must be considered when squamous cells are identified on endometrial samplings.

Vulvar malignant melanoma associated with human papillomavirus DNA: report of two cases and review of literature.

Oncogenic human papillomavirus (HPV) types such as HPV 16 are known to play a crucial role in the development of anogenital carcinomas. The etiology of anogenital malignant melanoma is unknown. We report two case of vulvar malignant melanoma in which multiple HPV types including HPV 16 and putative novel HPV types (alb-1, alb-2, alb-7, and alb-10) were identified by degenerated nested polymerase chain techniques (polymerase chain reaction) in both the malignant melanoma and surrounding skin. One melanoma was associated with lichen sclerosus, and the other, with melanoma in situ and pigmented vulvar squamous papillomatosis. These melanomas harbored HPV types alb-7, and HPV 16 as well as alb-1, respectively. HPV types 16, 20, 21, 36, alb-2, and AJ001060 were detected in vulvar skin affected by lichen sclerosus. Vulvar squamous papillomatosis harbored HPV types 28 and alb-10. HPV 16 was physically integrated into the host genome in lichen sclerosus skin and possibly in the melanoma associated with pigmented vulvar squamous papillomatosis. Twenty-two percent (4 of 18) of normal control specimens from skin tumor excisions were found to harbor HPV DNA (HPV types 3, 54, and alb-7); none of these control samples harbored multiple HPV DNA. These findings of multiple HPV DNA and integrated HPV 16 in skin associated with vulvar malignant melanoma indicate that HPV may play a role in the development of vulvar malignant melanoma. The role of HPV could be either direct through infection of melanocytes or indirect as a cofactor with free radicals in chronic fibroinflammatory vulvar disorders such as lichen sclerosus.