Comparative Pathology of Proliferative Lesions of the Urinary Bladder

Abstract

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 carcinogenesi s 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 preneoplasti c and neoplastic lesions arise throughou t 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 submucosa l mesenchyma l lesion present in some strains of mice. In addition, eosinophilic and clear inclusions in the super cial 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 carcinogen s 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 understandin g of the carcinogenic process in the urothelium as it pertains to human diseases.

Persistent uroplakin expression in advanced urothelial carcinomas: implications in urothelial tumor progression and clinical outcome

“…Fortunately, not all urothelial carcinomas carry the same risk of reaching the incurable stage. In fact, there is increasing evidence to suggest that at least two major carcinoma variants exist: the low-grade, superficial papillary tumors and the high-grade invasive tumors (3)(4)(5)(6)(7)(8)(9). The former frequently recur, but relatively few of them progress to muscle-invasive stages.…”

Differential Expression of Cell Cycle Regulators in Phenotypic Variants of Transgenically Induced Bladder Tumors: Implications for Tumor Behavior

“…In the United States, it ranks as the fifth most frequent neoplasm with about 54,000 new cases diagnosed annually (1). In the developed countries where schistosomiasis is not a problem, bladder neoplasias are predominately of the transitional cell carcinoma type, which is heterogeneous, exhibiting various histologic morphologies and biological behaviors (2)(3)(4). Seventy percent to 80% of transitional cell carcinomas present as low-grade, superficial papillary tumors that frequently recur, but rarely progress to the muscle-invasive stage.…”

Mutation Spectra of Kras and Tp53 in Urethral and Lung Neoplasms in B6C3F1 Mice Treated with 3,3′,4,4′-Tetrachloroazobenzene

“…Although a rare occurrence, bladder carcinomas in mice have been shown to arise through a sequence of morphological changes studied and described in animals treated with N-butyl-N-(4-hydroxybutyl)nitrosamines (Becci et al 1981;Ogawa et al 1998). The sequence of changes begins with the formation of nonpapillary dysplastic lesions, progressing to carcinoma in situ and then to invasive and metastatic carcinoma (Cohen 2002). Correlation of the morphological features of neoplasia with genetic changes has shown that mutations in the Tp53 gene occur in dysplastic and carcinomatous lesions in approximately 70% of mice (Ogawa et al 1998;Morimura et al 1999).…”