A Comparative Analysis of Lichen Sclerosus of the Vulva and Lichen Sclerosus That Evolves to Vulvar Squamous Cell Carcinoma

Abstract

Lichen sclerosus (LS) is a chronic inflammatory disease of unknown cause which is found most often in the vulvar region. Vulvar LS has been associated with squamous-cell carcinoma (SCC) of the vulva; estimates of the prospective risk of malignant transformation range from 3% to 5%. In this study, the proliferative index was determined using the cell proliferation marker Ki67 and expression of the tumor suppressors p16 and p53 was quantified in 8 women with histologically confirmed vulvar LS who, after 10 months to 9 years of follow-up, developed vulvar SCC. A comparison group consisted of 8 women with vulvar LS who did not develop cancer during follow-up for 9 years or longer. Immunoperoxidase staining utilized the monoclonal antibody MIBI. All patients described vulvar itching and/or burning. Mean ages were approximately 60 years for both groups of patients. Nuclear atypia was observed in epidermal keratinocytes in 2 of the 8 women with unchanged vulvar LS and in 5 of those who developed SCC, not a statistically significant difference. All cancers were of the keratinizing type with LS present in the nearby skin. Significantly higher MIBI labeling indices were found in cases evolving to vulvar SCC than in those that remained unchanged. The mean p53 labeling index was also significantly greater in evolving than in nonevolving cases of vulvar LS, but there was no such difference in pl6-positive staining between the 2 groups. Suprabasilar extension of p53 was observed in half of the evolving cases and in a single nonevolving case. All cases of evolving LS and none of those that did not become cancerous exhibited at least 2 of 3 characteristics: a MIBI labeling index (LI) exceeding 50%; a p53 LI exceeding 70%; suprabasilar extension of p53. Immunohistochemical staining for MIBI and p53 may help to identify those women with vulvar LS who are relatively likely to develop SCC. Periodic status checks or adjunctive biopsies would be appropriate for these patients.