Extramammary Paget's Disease Mimicking Squamous Cell Carcinoma In Situ: The Diagnostic Challenge of Recalcitrant Anogenital Lesions

Extramammary Paget's disease (EMPD) is a rare intraepithelial adenocarcinoma that arises predominantly in apocrine gland-rich areas. Its clinical presentation is non-specific, frequently leading to erroneous clinical diagnoses, diagnostic delay, and prolonged morbidity. A 77-year-old female presented with a 10-year history of a dermatosis affecting the trunk, external genitalia, and the inner side of the right thigh, characterized by three erythematous-squamous plaques (1 to 4 cm in diameter). The patient had a previous histopathological diagnosis of squamous cell carcinoma in situ and was treated with topical 5% 5-fluorouracil for six months. Due to recalcitrance to therapy, a new incisional biopsy was performed on the thigh lesion. Histopathology revealed large, pleomorphic cells with clear cytoplasm and pagetoid migration. Immunohistochemistry showed positivity for CK7 and negativity for CD44, supporting the diagnosis of EMPD. The patient was subsequently referred for Mohs micrographic surgery. Taking new biopsies for recalcitrant lesions is critical. An appropriately selected, broad immunohistochemical panel is a fundamental tool to differentiate intraepidermal malignancies in complex anogenital cases.