Non-urothelial and urothelial variants of bladder cancer

Non-urothelial bladder cancers make up a rare minority of all genitourinary (GU) tract histologic cancers since urothelial cancer (UC) makes up the most common histologic subtype. Bladder cancer variant histology (BCVH) or urothelial variants also occur rarely though distinction is important given aggressive presentation and natural history. While methods for diagnosis and treatment of typical urothelial cancers (UC) are well-established, there are no clear guidelines with regard to the diagnosis of non-urothelial bladder cancers, which often results in misdiagnosis and treatment delay. This review will focus on the clinicopathologic characteristics of the most common non-urothelial bladder cancers, to be distinguished from bladder cancer variant histology containing a UC component. The role of genomics in non-urothelial bladder cancers is evolving and the use of biomarkers to guide the diagnosis and treatment of these tumors remains a key area of unmet need. Treatment of these cancers will be discussed in a companion review.