What is the pathophysiology of clear cell renal cell carcinoma (CCRCC)?

Updated: Mar 11, 2019
  • Author: Ronald J Cohen, MB, BCh, PhD, FRCPA, FFPATH; Chief Editor: Liang Cheng, MD  more...
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Clear cell renal cell carcinoma (CCRCC) is proposed to arise from epithelial cells of the proximal convoluted tubules of the nephron, within the renal cortex. [1, 18] Extension into the renal sinus is the most common pathway of spread for most histologic types of RCC because no connective tissue separates the cortical columns of Bertin from the abundant lymphatics and vasculature within the sinus fat. [19]

CCRCCs have a higher propensity for vascular invasion than for lymphatic invasion, [20] with malignant cells found within small intrarenal veins even in 18-29% of organ-confined tumors. [21, 22] Thus, for CCRCC, invasion into the renal sinus usually involves extension within the renal vein, leading to a higher propensity for distant metastasis than for locoregional spread and involvement of the regional lymph nodes, which are more common pathways of spread in chromophobe and papillary RCC, respectively. [21, 23, 24, 25]

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