Clear cell renal cell carcinoma: Validation of WHO/ISUP grading



In 2012, the International Society of Urological Pathology (ISUP) introduced a novel grading system for clear cell and papillary renal cell carcinoma (RCC) based upon increasing nucleolar prominence in grades 1 to 3, with the presence of extreme nuclear pleomorphism and/or tumour giant cells and/or sarcomatoid and/or rhabdoid differentiation as criteria for grade 4. This system is now incorporated in the latest World Health Organization renal tumour classification, being designated WHO/ISUP grading.


This study was undertaken to compare WHO/ISUP and Fuhrman grading and to validate WHO/ISUP grading as a prognostic parameter in a series of clear cell RCC. Analysis of 681 cases of clear cell RCC showed that 144 tumours could not be assigned a Fuhrman grade on the basis of ambiguous grading features.


The application of WHO/ISUP grading resulted in a general down-grading of cases when compared with Fuhrman grading. In a sub-group of 376 cases, for which outcome data were available, 9.3% were WHO/ISUP grade 1, 50.0% were grade 2, 24.2% grade 3 and 16.5% grade 4, while the distribution of Fuhrman grades was 0.4% grade 1, 48.7% grade 2, 29.4% grade 3 and 21.5% grade 4. There were no recurrence/metastases amongst patients with WHO/ISUP grade 1 tumours and there was a significant difference in outcome for WHO/ISUP grades 2, 3 and 4. For Fuhrman grading the cancer-free survival was not significantly different for grade 2 and grade 3 tumours. On multivariate analysis WHO/ISUP grade and pT staging category were found to retain prognostic significance.

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