Pathology and molecular pathogenesis of renal cell carcinoma

Objectives: in this review, we summarise the World Health Organization (WHO) classification of renal cell carcinomas (RCCs) alongside grading and staging systems. General applications of immunohistochemistry, cytogenetics, and cDNA microarrays were reviewed with their implications in tumour diagnosis, prognosis, and therapy. Results: RCCs are classified according to the 2004 WHO classification, which defines three main histopathologic tumour subtypes with distinct clinical behaviour and underlying genetic defects: conventional (clear cell), papillary, and chromophobe RCC. Histopathologic classification and specific genetic mutations are crucial in distinguishing between familial and nonfamilial tumours. The most common four-tiered Fuhrman nuclear grade system is recommended for all types of RCC. Tumour grade is assigned according to the highest grade present; staging is assigned using the Union Internationale Contre le Cancer/American joint Committee on Cancer 2002 classification. Conclusions: Prognosis of patients with RCCs is most accurately predicted by TNM stage. Within stages, Fuhrman grade has a strong predictive value. Although not considered in nuclear grading, sarcomatoid dedifferentiation is a severely negative event for all RCC subtypes. Histologic subtypes of RCCs are not independent prognostic factors comparable with TNM stage and Fuhrman grade. Histologic coagulative tumour necrosis was an independent prognostic factor of outcome for clear cell and chromophobe RCC. Immunohistochemical panels including RCC marker, CD10, and KIT are now available for differential diagnosis of the distinct RCC subtypes. Genetic studies have improved understanding of subtypes, offering a promising approach for clinical diagnosis, prognosis, and possibly therapy. Urologists should be aware that currently many molecular analyses can be performed on RCCs, and when feasible, fresh samples sent to the pathologist. (c) 2006 European Association of Urology. Published by Elsevier B.V. All rights reserved.