Comparing World Health Organization/International Society of Urological Pathology Grading and Fuhrman Grading with the Prognostic Value of Nuclear Area in Patients with Renal Cell Carcinoma

Maj Rabjerg,Niels Marcussen,Birte Engvad,Oke Gerke

doi:10.3390/uro1010002

Abstract

This study was undertaken to compare Fuhrman grading with World Health Organization/International Society of Urological Pathology (WHO/ISUP) grading and stereologically measured nuclear area in patients with Clear Cell Renal Cell Carcinoma (ccRCC) or Papillary Renal Cell Carcinoma (PRCC) and to evaluate the independent predictive value of Fuhrman, WHO/ISUP and stereologically measured nuclear area combined with necrosis in a series of patients with ccRCC in relation to cancer-specific survival. In all, 124 cases of ccRCC and PRCC were included. All slides were blindly scored by two trained pathologists according to the Fuhrman and WHO/ISUP grading systems. Nuclear measurements were performed on digitally scanned slides in Visiopharm® and correlated to survival. Analysis of ccRCC and PRCC cases showed that application of WHO/ISUP grading resulted in a significant downgrading of cases from G2 to G1, when comparing with Fuhrman grading. Neither of these patients experienced progression. Cancer specific survival estimates in 101 ccRCC patients showed that WHO/ISUP grading was slightly superior in predicting cancer-specific survival. Novel models included WHO/ISUP grading and mean nuclear area (MNA) each of which combined with necrosis. Both demonstrated an increased ability to predict cancer-specific survival. The study demonstrates that WHO/ISUP grading provides superior prognostic information compared to Fuhrman grading and stereologically measured nuclear area. Necrosis in combination with either WHO/ISUP grading or MNA adds additional prognostic information.

Highlights

Renal cell carcinoma (RCC) is a neoplasm with widely varying prognosis, from an aggressive neoplasm, with metastasis at presentation, to a slowly growing neoplasm that can be observed safely for years [1]
We investigated the prognostic significance of the Fuhrman grading system, the World Health Organization (WHO)/ISUP grading system, and the correlation of nuclear morphometry to clinical outcome together with two novel, modified grading systems in Clear Cell Renal Cell Carcinoma (ccRCC)
We demonstrated that the WHO/ISUP grading system is superior in predicting cancer-specific survival

Summary

Introduction

Renal cell carcinoma (RCC) is a neoplasm with widely varying prognosis, from an aggressive neoplasm, with metastasis at presentation, to a slowly growing neoplasm that can be observed safely for years [1]. The overall 5-year progression-free survival rate is 70% and the cancer-specific mortality rate is 24% [2]. Only morphological features such as tumor size, vascular invasion, necrosis, stage and grade are routinely utilized in an effort to predict outcome [3,4]. That of Fuhrman et al [5], published in 1982, has achieved widespread use throughout the world in clinical routine pathology. It is a 4-tiered grading system, which is based primarily on the simultaneous

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