Immunohistochemical Expression of p63 and GATA3 in Lymphomas of the Urinary Bladder: A Clinicopathologic Study of a Potential Diagnostic Pitfall

Urinary bladder lymphomas are rare and may mimic urothelial carcinoma by morphology or unexpected expression of putative "urothelial" markers such as p63/ GATA3, the latter of which has not been thoroughly explored. Herein, we evaluate the clinicopathologic features of bladder lymphomas and assess the incidence of p63/GATA3 expression. A multi-institutional review identified 28 bladder lymphomas. Slides were re-reviewed for lymphoma subtype, growth pattern, urothelial colonization, and concurrent urothelial carcinoma. Clinical features recorded including age, presentation, procedure type, and cystoscopic impression. Immunohistochemistry for p63 and GATA3 was performed and semi-quantitatively scored for staining intensity and extent. The cohort included 28 tumors (mean age 71 years; male-to-female ratio = 4:3), most of which were primary bladder lymphomas (68%). Diffuse large B-cell lymphoma was the most common subtype (53% overall). A diffuse growth pattern predominated (93%), and 32% demonstrated colonization of the overlying urothelium. Concurrent urothelial carcinoma was present in 11% of tumors. By immunohistochemistry, 57% of lymphomas showed p63 positivity and 50% showed GATA3 positivity, with dual expression in 43%. p63/GATA3 expression occurred across multiple lymphoma subtypes. Staining intensity/extent was generally low to moderate but potentially misleading in specimens with sheet-like growth or urothelial colonization. Lymphomas involving the bladder frequently show morphologic and immunophenotypic overlap with urothelial carcinoma including diffuse architecture, urothelial colonization, and p63/GATA3 expression. These shared features constitute a significant diagnostic pitfall with potential therapeutic consequences. Awareness of this overlap and use of a broad immunohistochemical panel (eg, CD45, pankeratin) are essential for accurate diagnosis in unusual bladder tumors.