Melanoma associated with pseudoepitheliomatous hyperplasia: a case series and investigation into the role of epidermal growth factor receptor

Background:  Pseudoepitheliomatous hyperplasia (PEH) is a reactive epithelial proliferation that occurs in response to underlying infectious, inflammatory, and neoplastic conditions. The histologic features of PEH may simulate squamous cell carcinoma and may obscure an underlying malignant process. The association of PEH with benign melanocytic nevi is well described in the literature. However, reports documenting the association of PEH with melanoma are rare. Methods:  We examined the demographic and histologic features in 13 cases of melanoma in association with PEH. In addition, we evaluated the possible pathogenic role of epidermal growth factor receptor (EGFR) using immunohistochemical methods. Results:  In each case, histologic examination revealed epidermal hyperplasia with irregular cords of well-differentiated epithelial cells extending into the dermis and infiltrating the melanoma. Although overlap existed, two patterns of epidermal hyperplasia were noted. The majority of cases (69%) exhibited acanthosis, hyperkeratosis, papillomatosis, and irregular infiltrating epithelial cords with squamous eddies. The remaining cases demonstrated basaloid acanthosis, laminated orthokeratosis, and horn cysts. EGFR immunohistochemical studies revealed strong staining within the basal layer of the epithelium, with no discernible difference between the hyperplastic epithelium overlying the melanoma cells and adjacent normal skin. Immunostaining among the melanoma cells was absent to weak in each of the cases. All cases exhibited intense EGFR immunoreactivity in macrophages underlying the epidermal lesions. Conclusions:  Melanoma is capable of presenting in a variety of histologic guises, including a pattern with PEH. The etiology of PEH, as rarely seen in conjunction with melanoma, unlikely involves EGFR and remains to be elucidated.