Spindle cell lesions of the urinary bladder are uncommon, but when encountered in clinical practice, pose a difficult diagnostic challenge as the differential diagnostic considerations are vast. Pseudosarcomatous processes significantly overlap with malignant
tumors (sarcomatoid urothelial
carcinoma and
leiomyosarcoma) in their morphology and published immunohistochemical profile [pancytokeratin pan (CK), smooth muscle actin (SMA), and
desmin]. p63 has been studied rarely and CK 5/6 and CK 34betaE12 have not been analyzed in the bladder in this diagnostic context. In the current study, 45 typical examples of spindle cell lesions [10 pseudosarcomatous myofibroblastic proliferations (PMP), 22 sarcomatoid urothelial
carcinomas, and 13
smooth muscle tumors] of the urinary bladder were immunostained with a panel containing broad spectrum anticytokeratin
antibodies (OSCAR or AE1/AE3), as well as
antibodies to CK 34betaE12, CK 5/6, p63, SMA, and
anaplastic lymphoma kinase (ALK). The immunoreactivity was as follows: PMP-CK (OSCAR) 7/10 (70%), CK (AE1/AE3) 7/9 (78%), CK 34betaE12 0/10 (0%), CK 5/6 0/9 (0%), p63 0/9 (0%), SMA 10/10 (100%), ALK 2/10 (20%); sarcomatoid urothelial
carcinoma-CK (OSCAR) 15/22 (68%), CK (AE1/AE3) 14/20 (70%), CK 34betaE12 5/20 (25%), CK5/6 6/22 (27%), p63 11/22 (50%), SMA 16/22 (73%), ALK 0/22 (0%); and
smooth muscle tumors-CK (OSCAR) 7/13 (54%), CK (AE1/AE3) 7/12 (58%), CK 34betaE12 0/12 (0%), CK 5/6 0/12 (0%), p63 3/13 (23%), SMA 11/13 (85%), ALK 0/13 (0%). Positivity for
keratin was typically focal to moderate in
smooth muscle tumors and more commonly moderate to diffuse in sarcomatoid
carcinomas and PMP. Our data indicate that there is significant immunohistochemical overlap between the different spindle cell lesions, each of which has unique clinicopathologic, prognostic, and therapeutic ramifications. Within the context of morphology, an immunohistochemical panel composed of
broad-spectrum antibodies to
cytokeratin as well as
antibodies to SMA, ALK, p63, and CK 5/6 will be a useful diagnostic adjunct: a combination of pankeratin, SMA, and ALK positivity favors PMP; expression of several
cytokeratin and especially CK 34betaE12 and CK 5/6 with p63 favors sarcomatoid
carcinoma and SMA positivity with overall absence of other markers favors
leiomyosarcoma.