The Role of Immunohistochemistry in the Distinction of Invasive Plasmacytoid Urothelial Carcinoma from its Histologic Mimics

Author(s): McKenney JK, Sangoi AR, Gokden N

Plasmacytoid urothelial carcinoma is a rare and aggressive variant of bladder cancer that is characterized by infiltrating neoplastic cells that closely resemble plasma cells. It may mimic plasmacytoma, lymphoma, and carcinomas such as lobular carcinoma of breast and poorly differentiated carcinomas of gastrointestinal tract secondarily involving the bladder. There is limited data regarding the comparative immunophenotypes of these morphologically similar tumors. The surgical pathology and consultation files at three institutions were searched for plasmacytoid urothelial carcinoma, lobular breast carcinoma and diffuse or signet ring type gastrointestinal carcinoma from 1998 to 2010. H&E slides of 31 cases were reviewed to confirm diagnoses. A focused immunohistochemical panel including antibodies against E-Cadherin, P63, P53, CD138, MUM-1, estrogen receptor (ER), progesterone receptor (PR), GCDFP-15, CA 125, cytokeratin 7 (CK 7), cytokeratin 20 (CK 20), S100p and GATA3 was performed. Percent immunoreactivity was scored semi-quantitatively. All plasmacytoid urothelial carcinomas (n=11) showed immunoreactivity for CD138 and P53, but were negative for MUM-1, ER, PR, and GCDFP-15. E-Cadherin was completely lost in 25% of cases, and nuclear P63 was lost in 55% of cases. 99% had CK7 expression while 73% expressed CK20. GATA3 was expressed in 73% and S100p was expressed in 64% of cases. Lobular breast carcinomas (n=10) were immunoreactive for ER (100%), PR (60%), GCDFP-15 (90%), CK 7 (100%), P53 (60%), CD 138 (100%), CA 125 (20%), GATA3 (100%), S100p (40%), but were negative for MUM-1, P63, E-cad, and CK 20 in all cases. Diffuse/signet ring type gastrointestinal carcinomas (n=10) were immunoreactive for CD138 and E-cad, but negative for ER, PR and GCDFP-15 in all cases. Other variably positive markers in diffuse/signet ring type gastrointestinal carcinoma included P53 (90%), P63 (30%), CA125 (10%), CK 7 (60%), and CK 20 (80%), GATA3 (10%), S100p (50%). In summary, this study shows that the typical immunoprofile of plasmacytoid urothelial carcinoma is CD138 (+), CK7/20 (+), GATA3 (+), S100p (+) and MUM-1 (-), ER/PR/GCDFP-15 (-). The absence of MUM-1 staining in plasmacytoid urothelial carcinoma would be helpful in the distinction from plasma cells and lymphocytes. Diffuse/signet ring type gastrointestinal carcinoma has a variable immunoprofile which overlaps significantly with plasmacytoid urothelial carcinoma. P63 and E-cad expression in a subset of plasmacytoid urothelial carcinoma and negative ER, PR and GCDFP-15 stains may be useful in the distinction from lobular breast carcinoma.