Penile intraepithelial neoplasia with pagetoid features: report of an unusual variant mimicking Paget disease

SummaryPrecancerous lesions of the penis frequently share the morphologic features of the invasive counterpart. We have recently subclassified penile intraepithelial neoplasia into differentiated, warty, and basaloid subtypes, each one with distinctive microscopic morphology. Nevertheless, in our experience, some cases depart from this classification scheme and show unusual morphologic features, hindering the proper diagnosis on routine morphology alone. Herein we present a case of penile intraepithelial neoplasia with a pagetoid growth pattern, closely mimicking Paget disease. We describe the necessary steps to reach the final diagnose, including the use of immunohistochemistry for cytokeratin (CK) 7, CK20, CK34βE12, CAM 5.2, AE1/AE3, CEA, S100, Melan-A, and p63. We also discuss other differential diagnoses that should be considered such as malignant melanoma and urothelial carcinoma in situ with pagetoid spread and less common lesions such as pagetoid dyskeratosis, clear cell papulosis, and mucinous metaplasia.