Utility of GATA-3 and Cytokeratin 5/6 Immunostains in Separating Condyloma Acuminatum Arising in the Urinary Tract From Non-Invasive Papillary Urothelial Carcinoma

Background Condyloma acuminatum is a squamous epithelial lesion which uncommonly involves the urinary tract. In this location, non-invasive papillary urothelial carcinoma constitutes one of the main differential diagnoses with significant prognostic and therapeutic implications. To date, no ancillary immunohistochemical stain has been described to differentiate these two entities. We assess the utility of cytokeratin 5/6 (CK5/6) and GATA-3 immunohistochemistry in distinguishing condyloma acuminatum from non-invasive papillary urothelial carcinoma. Design We reviewed 9 condylomata acuminata involving the urinary tract, 12 low-grade and 8 high-grade non-invasive papillary urothelial carcinomas. CK5/6 immunostaining was performed in all cases. GATA-3 immunostaining and low-risk human papilloma virus (HPV) chromogenic in situ hybridization was performed in all condyloma cases and 2 urothelial carcinomas with squamous differentiation. Results 8/9 condylomata acuminata were positive for low-risk HPV. All condylomata acuminata exhibited strong full-thickness cytoplasmic staining for CK5/6. In 10 of 12 low-grade non-invasive papillary urothelial carcinomas, CK5/6 expression was continuous and limited to the basal cell layer, while it was patchy and limited to the basal cell layer in all 8 high-grade non-invasive papillary urothelial carcinomas. Two low-grade non-invasive papillary urothelial carcinomas showed focal full-thickness CK5/6 expression in the areas of squamous differentiation. These 2 cases were negative for low-risk HPV. GATA-3 immunostaining was positive in all condylomata acuminata. Conclusions CK5/6 immunostaining is a useful and simple tool that can help separate low-grade and high-grade non-invasive papillary urothelial carcinomas from condyloma acuminatum involving the urothelium-lined organs. GATA-3 has no discriminatory role between condyloma acuminatum and papillary urothelial carcinomas.