Grading of urothelial carcinoma of the bladder

 Introduction. Histological grading system is an important prognostic factor of bladder cancer. Grading of urothelial carcinoma has been a matter of debate since the three-grade system was introduced in 1973.

Objective. Optimization of the grading system for urothelial carcinoma.

Materials and methods. An analysis of literature devoted to evaluation of diagnostic significance, variability and interobserver reproducibility of the existing classifications of urothelial cancer of the bladder proposed in 1973, 1998, 1999 and 2004.

Results. The classification proposed in 1973 is the most popular and time honored method of grading bladder tumors. In 1998 it was modified by the International Society of Urological Pathology. In 1999 the World Health Organization (WHO) approved a new classification which preserved the three-grade system but differed from the previous ones. According to this new classification, tumors could fall into the following categories: papilloma, papillary urothelial neoplasm of low malignant potential, urothelial carcinoma of I, II, and III malignancy grade. The definition of papilloma was identical in all of these classifications. In 2004 a new WHO classification was introduced in which non-invasive urothelial tumors were subdivided into papilloma, papillary urothelial neoplasm of low malignant potential and low and high grade carcinoma. All of the proposed grading systems had a certain level of subjectivity and interobserver reproducibility, but reproducibility between unfamiliar pathologists was considerably higher than in groups of pathologists who had studied or worked together. Importantly, the 2004 WHO classification aimed to provide a detailed explanation of histological criteria for each diagnostic category and therefore improve reproducibility between different pathologists. However, no improvement of reproducibility in comparison with the 1973 WHO classification was observed. Moreover, among the pathologists better reproducibility of the 1973 WHO classification was registered compared to the 1999 and 2004 classifications. Reproducibility of the papillary urothelial neoplasm of low malignant potential diagnosis was only 48 %. At the same time, reproducibility of the 1973 WHO classification too has its problems. The biggest criticism is ambiguity in the diagnostic criteria of the 3 grades of urothelial carcinoma.

Conclusions. Standardization of the grading system of superficial bladder cancer allows to validate comparison between treatment outcomes in different centers. Introduction of the 2004 classification is the first step to treatment and monitoring standardization, but all of the classifications proposed by the WHO have shortcomings caused by considerable heterogeneity of papillary urothelial neoplasms. Significant interobserver reproducibility between papillary urothelial neoplasm of low malignant potential and low grade papillary urothelial carcinoma shows inadvisability of creating a separate diagnostic category for papillary urothelial neoplasm of low malignant potential. 

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