Development and progression of urothelial carcinoma

Urothelial carcinomas are well known to feature multifocal development in the urinary tract, both synchronously and asynchronously. This phenomenon can be explained by either seeding of cancer cells in the urinary tract or field cancerization. As there are two characteristic morphological patterns of urothelial carinomas, papillary and nodular, published papers were here reviewed to understand the development and progression of urothelial carcinoma regarding multifocality due to seeding or field changes with reference to the type of urothelial carcinoma. From animal experiments using rats, mice and dogs treated with N-butyl-N-(4-hydoroxybutyl) nitrosamine, and from pathological observation of human cystectomy specimens on step-sectioning and molecular analysis, nodular carcinomas appear to either develop via papillary carcinomas or de novo. Clinical aspects of multifocal tumor development are outside of the scope of this review, although an understanding of the mechanisms underlying multifocality and the papillary/nodular morphological relationship is important to determine follow-up strategies for patients treated for primary urothelial carcinomas and for reconstruction of the urinary tract after cystectomy.