Renal Cell Carcinoma is a silent killer – it does not have many noticeable symptoms and the few that it does have are relatively nonspecific. These symptoms can include weight loss, flank pain or discomfort, abdominal or back mass, or blood in the urine. Advanced disease can produce additional symptoms that are not initially ascribed to the kidney including fever, hypertension, amyloidosis, leukemoid reactions, hypercalcemia, and polycythemia. Due to the vagueness of these symptoms, unfortunately many cases are not diagnosed until the malignancy has become rather advanced; however due to recent advances in imaging now almost 70% of cases are discovered on abdominal imaging being performed for other reasons.
There are approximately 13.6 cases of renal cell carcinoma per 100,000 persons, and the average age at disease onset is 64. There are approximately 30,000 new cases per year and 12,000 deaths per year from the disease. Males are twice as likely to be affected. Renal cell carcinoma has a 5 year survival rate of 68.4%; however if the tumor is caught before it spreads the rates are much better. Localized disease has a 5 year survival rate of 90.4%, regional disease has a 5 year survival rate of 62.3%, and metastatic disease has a 5 year survival rate of 10.4%. The most significant risk factor for renal cell carcinoma is tobacco use.
Histologically, there are 4 different kinds of renal cell carcinoma: Clear Cell, Papillary, Chromophobe, and Collecting Duct. Clear cell accounts for 70-80% of all renal cell carcinomas and is the type that will be discussed here. The tumor is composed of cells with only a clear or granular cytoplasm, hence its name. There are both sporadic and familial cases of the malignancy, with the majority of cases being sporadic. Though the majority of cases arise spontaneously, 98% of both sporadic and familial cases have a mutation or deletion in the VHL gene on the short arm of chromosome 3. The VHL gene is a tumor suppressor gene that codes for a protein that is part of an ubiquitin ligase complex in the kidney; its function is to “tag” unwanted and unneeded proteins for degradation. One of its targets, hypoxia-inducible factor 1 (HIF-1) is a protein that enables the cancer to gain multiple functions. HIF-1 is always active, and it increases the transcription and translation of multiple growth factors such as vascular endothelial growth factor, platelet derived growth factor, tumor growth factor alpha and tumor growth factor beta. It also upregulates the transcription of insulin-like growth factor 1, and by the addition of these various growth factors the tumor is able to both increase its size and blood supply.
Morphologically, most renal cell carcinomas grow in the upper or lower poles of the kidney and arise as unilateral, solitary, spherical masses. They tend to be yellowish, grayish, white masses that can distort the normal shape of the kidney. The yellowish coloration can be owed to the lipid rich contents of the cells and the grayish-white areas are usually areas of ischemic or necrotic tissue where the tumor has outgrown its vascular supply.
One of the interesting features of renal cell carcinoma is its tendency to invade the renal vein as a solid tumor mass. This mass can then proceed to invade the inferior vena cava, and has been known to grow into the right atrium of the heart, remaining a solid tumor mass directly growing out of the primary tumor in the kidney. When the tumor invades the renal vein and inferior vena cava it is termed a “tumor thrombi”, and a classification system has been built for these thrombi to help guide clinical and surgical management of the tumors. The classification system is typically divided into four classes, and is as follows: I) At the level of the renal vein or <2 cm above renal vein II) >2cm above renal vein but at or below the hepatic veins III) above hepatic vein but below diaphragm IV) above diaphragm. Tumor thrombi in classes I or II can usually be performed without cardiopulmonary bypass in a relatively healthy, hemodynamically stable patient but levels III & IV require cardiopulmonary bypass due to the involvement of the portal venous system and also due to atrial involvement in some instances of level IV tumor thrombi.
Crawford, John Lloyd and Garcia, G. Matthew, "A 67 Year Old Male with a Left Renal Cell Carcinoma Having a Tumor Thrombus Extending into the Inferior Vena Cava" (2010). Research Appreciation Day. Paper 3.