Secondary malignancy to bladder can either be by direct extension or by metastasis from a distant tumor site.
Most common sites of origin are colon (21%) (image A), prostate (19%) (image B), rectum (12%), uterine cervix (11%) and melanoma (rare).
Most secondary bladder tumors are gland-forming (adenocarcinoma); distinction from urothelial carcinoma is difficult when the tumor has a poorly differentiated morphology (no obvious glands).
Urothelial carcinoma is GATA3+ and uroplakin+ (but has low sensitivity) in contrast to the vast majority of secondary tumors.
Also urothelial carcinoma is typically CK7+, CK20+, p63+ (nuclear) and high molecular weight keratin (HMWK)+.
Colorectal adenocarcinoma may resemble bladder adenocarcinoma of enteric morphology (including presence of "dirty" necrosis), and both express the intestinal marker CDX2.
In contrast to colonic adenocarcinoma, bladder primary adenocarcinoma is nuclear β-catenin- (not all colonic adenocarcinoma though are positive) and often CK7+.
Poorly differentiated prostate adenocarcinoma that extends into the bladder can be diagnostically challenging.
In contrast to urothelial carcinoma, prostate carcinoma is PSA+ and PSAP+ (may be negative with poorly differentiated prostate carcinoma!) and is p63- and HMWK-.