Staging, Grading, and Emerging Prognostic Factors in Renal Cell Carcinoma

Renal cell carcinoma (RCC) makes up most adult kidney cancers. The classic presentation is a spherical, well-circumscribed mass, but fewer subtypes present as more infiltrative neoplasms. Both growth patterns can affect tumor staging and prognosis. Accordingly, this review will discuss the current status of staging, grading, and pathologic prognostication in RCC. Typically, the most important prognostic parameter in RCC is tumor stage. Pathologic staging categories (i.e., pT) are influenced by tumor size (pT1-pT2) and invasion of structures including renal sinus, perinephric fat, the renal vein or segmental branches, vena cava, or adjacent organs/structures (≥pT3). This invasion is prognostically important but can prove difficult to diagnose, due to the more common nodular rather than infiltrative pattern of RCC. In clear cell RCC, more than half of tumors over 5 cm and over 90% of tumors over 7 cm invade the renal sinus soft tissue, such that true pT2 clear cell RCC is rare. However, the size to invasion relationship is less clear for other RCC subtypes, some of which become large without invading structures (e.g., papillary RCC, chromophobe RCC), and others of which are infiltrative irrespective of size (e.g., renal medullary carcinoma, FH-deficient RCC). Histologic grading in recent years has evolved to focus mostly on prominence of the nucleolus. Other emerging assessments in RCC include tumor necrosis as a prognostic parameter (predominantly for clear cell RCC), architectural grades in clear cell RCC, and specific growth patterns in papillary RCC, such as microcystic growth. Overall, this review is aimed to serve as a guideline to the staging and grading of RCC in clinical practice, as well as highlight the potential challenges and pitfalls in this crucial interface between clinical management and diagnostic pathology.