Immunohistochemical Differentiation of Plasmacytoid Urothelial Carcinoma From Secondary Carcinoma Involvement of the Bladder

Plasmacytoid urothelial carcinoma (UC) is a rare variant of UC that can histologically mimic metastatic cancer involving the urinary bladder. A total of 45 cases of plasmacytoid UC were collected and reviewed histologically. The following immunohistochemical markers were performed: CDX2; polyclonal carcinoembryonic antigen (p-CEA); gross cystic disease fluid protein 15 (GCDFP-15); mammaglobin; estrogen receptor (ER); progesterone receptor (PR); GATA 3 and uroplakin II. In all cases, the plasmacytoid variant of UC lacked expression of ER and mammaglobin. In contrast, GCPDFP-15, PR, CDX2 and p-CEA showed positive staining in 11 (24.4%), 6 (13.3%), 8 (17.7%), and 22 (48.8%) cases, respectively. GCPDFP-15 was expressed in 4/8 female cases with 1 concurrently focally (+ 2) expressing PR. GATA 3 and uroplakin II was positive in 37/45 cases (82.2%) and 15/45 (33.3%) cases, respectively. A tissue microarray with 40 cases of infiltrating lobular carcinoma of the breast was stained for uroplakin II, and was negative in all cases. Tissue microarrays with 46 cases of gastric signet ring cell adenocarcinomas were all negative for GCDFP-15, ER, PR, GATA3, uroplakin II, and mammaglobin. A panel of stains including mammaglobin, ER, and uroplakin II is recommended to exclude metastatic lobular breast carcinoma to the bladder in cases where a conventional UC component is not present. Immunohistochemistry for CDX2 and p-CEA cannot be utilized to differentiate signet ring cell adenocarcinoma of the gastrointestinal tract from plasmacytoid UC; GATA3 or uroplakin II immunoreactivity can rule out a gastric primary given their negativity in signet ring cell adenocarcinoma of the stomach.