Clear cell renal cell carcinoma

Synonyms

3

Overview

The clear cell renal cell carcinoma (also called common, conventional or non papillary renal cell carcinoma, CCRCC), is a distinct subtype of renal cell carcinoma, possibly originating from mature renal tubular cells in the proximal tubule of the nehpron.

Symptoms

CCRCC can cause pain in the back, side, or abdomen, blood in the urine, and/or fever and weight.

CCRCC, once it has spread, can grow slowly or rapidly. Slowly growing tumors may not cause symptoms and may not need to be treated right away, but rapidly growing tumors will make the patient ill within weeks. 

Causes

A number of environmental and genetic factors have been studied as possible causes for renal cell carcinoma.

  • Cigarette smoking doubles the risk of renal cell carcinoma and contributes to as many as one third of all cases. The risk appears to increase with the amount of cigarette smoking in a dose-dependent fashion.
  • Obesity is another risk factor, particularly in women; increasing body weight has a linear relationship with increasing risk.(Ref: BJU International 2010;105:16-20)
  • Hypertension may be associated with an increased incidence of renal cell carcinoma.
  • Phenacetin-containing analgesia taken in large amounts may be associated with increased incidence of renal cell carcinoma.
  • There is an increased incidence of acquired cystic disease of the kidney in patients undergoing long-term renal dialysis; this predisposes to renal cell cancer.
  • Tuberous sclerosis
  • Renal transplantation: Acquired renal cystic disease of the native kidney also predisposes to renal cell cancer in renal transplant recipients.
  • VHL disease: This inherited disease is associated with renal cell carcinoma.

Diagnosis

The clear renal cell carcinoma shows a male preponderance of 2:1. The tumor mass of clear renal cell carcinoma is multicolored, with a predominantly yellow surface with white or gray foci. It usually shows a solid growth pattern, but in some cases cystic or alveolar appearance is seen. The cytoplasm is clear, due to an intensive intracytoplasmatic accumulation of glycogen and lipids. The nuclei are condensed and hyperchromatic. Electronmicroscopical features resembling the proximale tubule can be found i.e. brush border formation and basal infoldings. Tumor cells express antigens of the proximal tubule.

Variants can be assigned which are characterized by augmentation of mitochondria leading to a stronger eosinophilia or granularity, respectively, of the cytoplasm. Spindle-shaped/pleomorphic variants as a result of sarcomatoid transformation can also be found.

Treatment

  • Surgery - only curative option is complete resection of the tumor
  • Radiotherapy - For palliative management of inoperable symptomatic tumors and metastatic disease
  • Multikinase inhibitors - Used to improve survival in advanced disease - Sorafenib, Sunitinib, Temsirolimus, Everolimus
  • Biological therapies - Used to improve survival in advanced disease - Interleukin 2, Interferon