Management of Extramammary Paget Disease of the Male Genital Region: A Narrative Review and Two Case Reports

<b>Background/Objectives</b>: Extramammary Paget disease (EMPD) is a rare, slow-growing intraepithelial malignancy arising in apocrine gland-bearing skin, most commonly in the anogenital region. Although often confined to the epidermis, EMPD may be associated with synchronous or underlying malignancies and can progress to invasive disease, making early recognition and compre- hensive staging crucial. <b>Methods</b>: We review current knowledge on the epidemiology, molecular pathogenesis, diagnostic work-up and treatment of EMPD with a particular focus on male genital involvement, and illustrate key clinical issues with two cases of penoscrotal EMPD treated in our center. Clinically, EMPD typically presents as chronic erythematous, pruritic plaques that are frequently misdiagnosed as benign dermatoses, leading to diagnostic delays. <b>Results</b>: Histopathology with immunohistochemistry remains the diagnostic gold standard and guides the search for associated internal malignancies. Wide local excision and Mohs micrographic surgery are the mainstays of treatment, but recurrence is common owing to subclinical extension. Non-surgical modalities-including photodynamic therapy, topical imiquimod, radiotherapy and, in advanced disease, systemic chemotherapy, HER2 targeted agents and immune checkpoint inhibitors-provide additional options in selected patients. <b>Conclusions</b>: A multidisciplinary, biomarker driven approach is essential to individualize management and improve long-term outcomes in this challenging disease.