Comparative pathology of proliferative lesions of the urinary bladder

Bladder neoplasia in humans consists of 2 diseases, a low-grade papillary tumor that does not invade or metastasize, and a high-grade lesion that usually invades and metastasizes. Bladder carcinogenesis in rats is most like the low-grade, papillary tumor, although it eventually does progress and invade. In the mouse, models are available that mimic each of these disease processes. Preneoplastic lesions in humans and rodents include various types of hyperplasia, proliferative cystitis, and dysplasia. These preneoplastic and neoplastic lesions arise throughout the urothelium, from the renal pelvis to the urethra, although most commonly in the bladder. Rarely, benign and malignant mesenchymal lesions occur in rats and mice, with a unique submucosal mesenchymal lesion present in some strains of mice. In addition, eosinophilic and clear inclusions in the superficial layer of urothelium in mice, which do not appear to be associated with toxicity or carcinogenesis, have been reported. An approach to evaluation of carcinogenic mechanisms involved in the urothelium is presented. It focuses on distinguishing between DNA reactive carcinogens vs those that act by increasing cell proliferation. Although rodent models do not precisely mimic the human disease, they have provided useful models for furthering our understanding of the carcinogenic process in the urothelium as it pertains to human diseases.