Grading Chromophobe Renal Cell Carcinoma: Evidence for a Four-tiered Classification Incorporating Coagulative Tumor Necrosis

Background Although grading systems have been proposed for chromophobe renal cell carcinoma (ChRCC), including a three-tiered system by Paner et al (Paner GP, Amin MB, Alvarado-Cabrero I, et al. A novel tumor grading scheme for chromophobe renal cell carcinoma: prognostic utility and comparison with Fuhrman nuclear grade. Am J Surg Pathol 2010;34:1233–40), none have gained clinical acceptance, and the World Health Organization (WHO) currently recommends against grading ChRCC. Objective To validate a previously published grading scheme and propose a scheme that includes tumor necrosis. Design, setting, and participants A total of 266 patients who underwent nephrectomy for nonmetastatic ChRCC between 1970 and 2012 were reviewed for ChRCC grade according to the Paner system and coagulative tumor necrosis. Outcome measurements and statistical analysis Associations with cancer-specific survival (CSS) were evaluated using Cox proportional hazard regression models and summarized with hazard ratios (HRs). Results and limitations Twenty-nine patients died from RCC; the median follow-up was 11.0 (interquartile range 7.9–15.9) yr. ChRCC grade according to the Paner system was significantly associated with CSS, including the difference in outcome between grade 1 and 2 tumors. Among patients with grade 2 tumors, the presence of tumor necrosis helped delineate patients with worse CSS. As such, the Paner system was expanded to four tiers separating grade 2 into those with and without tumor necrosis. HRs for associations of the proposed grade 2, 3, and 4 tumors with CSS were 4.63 (p = 0.007), 17.8 (p Conclusions The expansion of a previously reported ChRCC grading system from three to four tiers by the inclusion of tumor necrosis helps further delineate patient outcome and can, therefore, enhance patient counseling following surgery. It also aligns the number of ChRCC grades with the WHO/International Society of Urologic Pathology four-tiered grading systems for clear cell and papillary RCC. Patient summary Chromophobe renal cell carcinoma is the third most common type of renal cancer, and unlike other renal cancers, there is no accepted prognostic grading system. In this study, we found that a grading system that included a pathologic feature of tumor necrosis could better define outcomes for patients with chromophobe renal cell carcinoma.