Lymphovascular and marginal invasion as useful prognostic indicators and the role of c-erbB-2 in patients with male extramammary Paget's disease: A study of 31 patients

Purpose: Extramammary Paget's disease (EMPD) is a rare intraepithelial neoplasm arising in skin that bears apocrine glands. We analyzed clinical, pathological and immunohistochemical staining patterns in 31 cases of EMPD to assess possible predictors of outcome, including patient age, sex, involved organs, surgical margin status, invasion depth, lymphovascular invasion, adnexal invasion, and immunoreactivity for cytokeratin 7 and 20, carcinoembryonic androgen, androgen receptor, p53, c-erbB-2 (Dako, Carpinteria, California) and Ki67. Materials and Methods: A total of 31 cases of EMPD were retrieved from the surgical pathology files of the department of pathology along with the medical records of the department of urology. Dermal invasion depth, tumor margin status, adnexal invasion and lymphovascular invasion were determined from the hematoxylin and eosin stained slides of each case. Results: Eight of the 31 cases (25.8%) experienced local recurrence. Two of 3 patients with and 6 of 28 without lymphovascular invasion experienced recurrence (p = 0.029). Dermal invasion significantly correlated with Her-2 over expression (Wilcoxon 2-sample test p = 0.0007). When the criteria of 1 and 5 mm invasion were applied, each validly correlated with Her-2 over expression. Her-2 over expression (grades 2 and 3) significantly correlated with p53 over expression (Wilcoxon rank test p = 0.0015). C-erbB-2 was positive in 51.6% of EMPD cases, in which it was strongly associated with dermal invasion and p53 over expression. Conclusions: The most valid prognostic factor in male EMPD for predicting late recurrence is lymphovascular permeation and marginal status.