Grading systems in renal cell carcinoma

Purpose: We reviewed updated literature data concerning several issues of renal cell carcinoma grading systems. Materials and Methods: We performed a nonsystematic review of the literature. Data were identified by a MEDLINE (R) search using a strategy including MeSH (R) and free text protocols. From the MEDLINE search we collected 184 records. Results: Although the original study was published in 1982, the independent predictive value of nuclear grades was only revealed in 2000 by the team from University of California-Los Angeles. Subsequently further data from our group and the group at the Mayo Clinic reconfirmed those findings, although similar cancer specific survival probabilities were noted among different grades. The prognostic relevance of nuclear grade justified the inclusion of that variable in algorithms and nomograms predictive of cancer specific survival, such as those provided by University of California-Los Angeles, the Mayo Clinic and Memorial Sloan-Kettering Cancer Center. Despite the routine clinical use of nuclear grade, several drawbacks have affected grading systems, such as interobserver and intra-observer reproducibility, and variability of the cancer specific survival probabilities stratified by grade. Several studies showed that intra-observer and interobserver agreement with regard to grade are only moderate with up shifting in all series. That issue might be due to the heterogeneity of renal cell carcinoma as well as to the lack of consensus about the minimal size of high grade tumor to be considered significant. Moreover, recent data underscore the role of histological subtypes. Conclusions: Grade is one of the most powerful prognostic factors in patients with renal cell carcinoma. The Fuhrman grading system is currently most widely used by pathologists in Europe and the United States. However, there is still a need for better standardization of nuclear criteria to improve interobserver reproducibility and a major consensus should be achieved by uropathologists.