True Papillae and Squamous Features in Prostate Carcinoma Represent a Potential Diagnostic Pitfall: Report of 3 Patients

Poorly differentiated prostate adenocarcinoma may closely mimic high-grade urothelial carcinoma, particularly when presenting as a bladder or prostatic urethral mass without clinical history or prostate-specific antigen (PSA) data. We describe 3 patients who presented with hematuria and bladder lesions strongly resembling invasive urothelial carcinomas on limited transurethral resection of the bladder (TURB) specimens. All lesions demonstrated papillae lined by high-grade multilayered epithelium with marked nuclear pleomorphism and brisk mitotic activity, features rarely seen in prostate carcinomas and more characteristic of urothelial carcinomas. One tumor showed squamoid differentiation. All specimens showed muscularis propria invasion. Clinical history available at the time of the biopsy indicated a prior TURB for urothelial carcinoma in 1 patient and a known history of prostate cancer in another one. On immunohistochemistry, tumors expressed androgen receptor and NKX3.1, focally PSA and diffuse pankeratin staining, with negative keratin 7, keratin 20, keratin 5/6, and GATA3; residual urothelium exhibited p40/p63 staining. These findings confirmed high-grade prostate adenocarcinoma involving the bladder. Upon diagnosis, a history of prostate cancer under androgen ablation therapy was revealed for 1 of the patients and a PSA level of 70 ng/ml for another 1. This series highlights an underrecognized morphologic pattern of prostate cancer that could lead to an erroneous diagnosis, particularly in the absence of PSA testing, complete clinical history or comprehensive immunostaining. Accurate distinction of poorly differentiated prostate carcinoma from urothelial carcinoma requires correlation with prior diagnoses and a focused immunohistochemical panel, as misclassification carries significant therapeutic implications. Pathologists should maintain awareness of this uncommon mimic.