LAUSR

Dear Editor We have read with interest the study by Borgmann et al. relating to the validation of Fuhrman grading (FG) for papillary renal cell carcinoma (RCC). The authors conclude that FG is a strong prognostic factor for cancer-specific survival in patients with papillary RCC [1]. Unfortunately, the manuscript is hampered by a number of issues that serve to seriously limit the validity of the results. In the introduction, the authors note that FG has been correlated with survival for clear cell RCC. In reality this is far from the truth as many studies have shown the fourtier grading system of Fuhrman does not predict outcome [2]. In some studies grouping of FG has been correlated with survival; however, in these studies grades are pooled which does not conform to the criteria of the Fuhrman classification [3]. Fuhrman grading requires the simultaneous assessment of three grading features and a recent study has confirmed that in > 20% of cases of clear cell RCC discordance amongst grading parameters prohibits assignment of a Fuhrman grade [4]. It is our experience that a similar number of papillary RCCs are ungradable. A major problem is that the study had no central review which the authors note is a real-world situation. This is somewhat surprising as multidisciplinary meetings with pathology review are standard clinical practice. It is also unfortunate that there is apparently no pathologist in the authorship, as the International Society of Urological Pathology grading system has now been endorsed by the World Health Organization and the WHO/ISUP grading system is now the worldwide standard for pathology reporting. The failure to review cases in the series means that the specific interpretation of FG criteria utilized by the reporting pathologists is unknown. It is noted that specimens were handled according to ISUP guidelines. This is somewhat surprising as some cases in the series predate the publication of the 2014 guidelines by 24 years. Our understanding of the prognostic significance of renal sinus invasion dates from 2000 and prior to this renal sinus sampling was not routinely undertaken, which means that a substantial proportion of cases will have been under-staged. The failure to review the cases also means that recently described morphotypes of RCC will be included in the series, including clear cell (tubulo)papillary RCC which is now recognized as the fourth most common RCC morphotype. In the discussion it is noted that Klatte et al. showed FG to be superior to nucleolar grading for papillary RCC [5]. Unfortunately that study, as well as the present study, failed to realize that in our evaluation of the prognostic significance of nucleolar prominence, as defined in the first three grades of the WHO/ISUP classification, grade 4 tumors were purposely omitted from the analysis [6]. It is, therefore, not surprising that Klatte’s analysis of four-tier FG, including high-grade poor-prognosis tumors, was statistically superior. Reference to the validating studies on WHO/ISUP grading clearly demonstrates that it outperforms FG for clear cell and papillary RCC [4, 6–10].