FOXP3+regulatory T-cells are abundant in vulvar Paget's disease and are associated with recurrence

Objective. To characterize clinical features of vulvar Paget's disease, and examine the quantity of immunosuppressive regulatory T-cells in vulvar Paget's tissue. Methods. Vulvar Paget's cases from 1992 to 2007 from two institutions were identified by pathology database search. Regulatory T-cells were identified with FOXP3 immunohistochemistry and quantified at the dermal-epidermal junction using image analysis software. Thirteen non-neoplastic inflammatory cases were stained for comparison. Results. Cases included 33 women treated for primary vulvar Paget's, and 7 referred at recurrence. Of the 24 primary cases with greater than 5 months follow-up, recurrence was documented in 12/24(50%). Eight women (20%) recurred multiple times, but no recurrences were invasive. Significantly more patients with positive margins developed recurrent disease (82% vs 23%, p = 0.01). Secondary neoplasms occurred in 10/40 (25%). FOXP3+ cells at the dermal-epidermal junction were quantified in 29 primary and 13 recurrent tissue samples. FOXP3+ cells were absent in surrounding normal vulvar skin. FOXP3+ cells averaged 66/HPF in primary vulvar Paget's and 66/HPF in recurrent Pager's, compared to 22/HPF in non-neoplastic inflammatory cases (p = 0.0003, p = 0.001). Primary cases with positive surgical margins had more FOXP3+ cells than those with negative margins (85 vs 49, p = 0.01). Recurrent cases with positive margins had more FOXP3+ cells than negative cases (84 vs 33, p = 0.06). FOXP3 levels in primary specimens were higher in cases which recurred (78 vs 35, p = 0.02). Conclusions. Increased regulatory T-cells may be associated with more extensive cases of vulvar Paget's disease that result in positive surgical margins and are associated with recurrence of disease, suggesting immunosuppression as a key factor. (C) 2010 Elsevier Inc. All rights reserved.