Answer: D
Histological Description: The tumor consists of sheets of cells. The tumor has a pseudopapillary appearance due to tumor necrosis away from the blood vessels. In contrast to true papillary formation, at the edges of the papillary appearing structures, there are necrotic cells and karryorrhectic debris. The tumor also has subtle rudimentary cribriform formation. Nuclei are relatively uniform with centrally located prominent eosinophilic nucleoli. Mitotic figures are fairly frequent.
Discussion: A common and critical differential diagnosis is between poorly differentiated urothelial carcinoma and prostate adenocarcinoma involving the bladder neck and even the trigone. Clinically, the two entities can be indistinguishable even to expert urologists. Some poorly differentiated prostate carcinomas lack significant PSA production further confounding the issue. Typically, prostate adenocarcinoma has more uniform nuclei with prominent nucleoli and relatively few mitotic figures. However, the key for pathologists is to recognize that poorly differentiated prostate adenocarcinoma can have pseudopapillary formation, increased mitotic figures, as well as in some cases pleomorphic giant cell features that overlap with the degree of cytological atypia seen in urothelial carcinoma. In uncommon cases, prostate adenocarcinoma can even colonize the urothelial surface further mimicking a bladder primary. The finding of cribriform glands strongly favors prostate adenocarcinoma, as urothelial carcinoma with glandular differentiation typically lacks cribriform glands. In the setting of a poorly differentiated tumor in the bladder neck and trigone, pathologists should have a low threshold to performing stains to differentiate between the two primaries.
Poorly differentiated prostate adenocarcinoma is variably and focally positive for prostate markers (PSA, PSMA, P501S, NKX3.1). The most sensitive and specific prostate marker is NKX3.1 A small percent of prostate adenocarcinomas are negative for PSA such that other prostate markers should be done before assuming PSA negative cancer is urothelial carcinoma. It is critical to have strong staining in the positive control of benign prostate tissue since prostate carcinoma shows lower expression. A pitfall is that occasional prostate adenocarcinomas can aberrantly express high molecular weight cytokeratin (HMWCK) in a non-basal cell distribution, less commonly seen with p63. GATA-3 with exceedingly rare exception is negative. AMACR (racemase) does not differentiate between prostate and urothelial carcinoma. The most sensitive and specific marker for urothelial carcinoma is GATA3 with fewer cases positive for thrombomodulin. Approximately 2/3rds of urothelial carcinoma are positive for HMWCK or p63, such that negative staining for these markers do not rule out urothelial carcinoma. Uroplakin II, although negative in prostate adenocarcinoma, is not that sensitive in high grade urothelial carcinomas. It is critical to recognize the difference between prostate adenocarcinoma and urothelial carcinoma since advanced high grade prostatic adenocarcinoma are treated with anti-androgen therapy, while advance urothelial carcinoma would be treated with chemotherapy +/- radical cystectomy.