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  • Renal Cell Carcinoma

    Renal cell carcinoma, or hypernephroma, is a type of kidney cancer that originates in the the lining of very small tubes (tubules) in the kidney that filter the blood and remove waste products.

    Epidemiology of Renal Cell Carcinoma

    Renal cell carcinoma is responsible for 3% of adult cancers, is the most common type of kidney cancer in adults and is responsible for approximately 90-95% of neoplasms arising from the kidney. It occurs most often in men ages 50-70, but unfortunately it also occurs in women. Renal cell carcinoma is also the most lethal of all the kidney cancers. It effects both kidneys in about 2% of cases, and it spreads easily (most often to the neighboring lymph nodes, the lungs-75%, the soft tissues-36%, the bones-20%, the liver-18%, or the brain-8%).  When the tumor is confined to the renal parenchyma (stage I) the 5-year survival rate is 80-85%; but this is lowered considerably when it grows beyond the confines of the kidney, and is reduced to a 5-year survival rate of less than 5% if the tumor has spread to other organs beyond the local lymph nodes.

     

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    Renal Cell Carcinoma Staging

    Staging of renal cell carcinoma is generally categorized by the Robson, histological, and genetic classification systems.

    The Robson Staging System of Renal Cell Carcinoma

    The Robson modification of the Flocks and Kadesky system is commonly used in clinical practice. This system was designed to correlate stage at presentation with prognosis. The Robson staging system is as follows:

    • Stage I - Tumor confined within capsule of kidney
    • Stage II - Tumor invading perinephric fat but still contained within the Gerota fascia
    • Stage III - Tumor invading the renal vein or inferior vena cava (A), or regional lymph-node involvement (B), or both (C)
    • Stage IV - Tumor invading adjacent viscera (excluding ipsilateral adrenal) or distant metastases

    The Tumor, Nodes, and Metastases (TNM) Classification System

    The major advantage of the TNM system is that it clearly differentiates between disease with tumor thrombi that spread disease via the blood from those with disease in the local lymph nodes.

    The TNM classification system is as follows:

    • Primary tumor (T)
      • TX - Primary tumor cannot be assessed
      • T0 - No evidence of primary tumor
      • T1 - Tumor 7 cm or smaller in greatest dimension, limited to the kidney
      • T2 - Tumor larger than 7 cm in greatest dimension, limited to the kidney
      • T3 - Tumor extends into major veins or invades adrenal gland or perinephric tissues but not beyond the Gerota fascia
      • T3a - Tumor invades adrenal gland or perinephric tissues but not beyond the Gerota fascia
      • T3b - Tumor grossly extends into the renal vein(s) or vena cava below the diaphragm
      • T3c - Tumor grossly extends into the renal vein(s) or vena cava above the diaphragm
      • T4 - Tumor invading beyond the Gerota fascia
    • Regional lymph nodes (N) - Laterality does not affect the N classification
      • NX - Regional lymph nodes cannot be assessed
      • N0 - No regional lymph node metastasis
      • N1 - Metastasis in a single regional lymph node
      • N2 - Metastasis in more than 1 regional lymph node
    • Distant metastasis (M)
      • MX - Distant metastasis cannot be assessed
      • M0 - No distant metastasis
      • M1 - Distant metastasis
    • AJCC stages
      • AJCC stage I - T1, N0, M0
      • AJCC stage II - T2, N0, M0
      • AJCC stage III - T1-2, N1, M0 or T3a-c, N0-1, M0
      • AJCC stage IV - T4; or any T, N2, M0; or any T, any N, M1
    • The division of patients with renal cell carcinoma into low-, intermediate-, and high-risk groups with or without metastases may be useful in choosing appropriate therapy for them.

    Renal Cell Carcinoma Histologic Subtypes

    The 5 histological subtypes of renal cell carcinomas include clear cell (75%), chromophilic (15%), chromophobic (5%), oncocytoma (3%), and collecting duct (2%) 

    Genetic Classification of Renal Cell Cancer

    Renal Cell Cancer Genetics

    Renal cancer occurs in both a sporadic (nonhereditary) and a hereditary form, and both forms are associated with structural changes of the short arm of chromosome 3 (3p). In addition, there are at least 4 hereditary syndromes associated with renal cell carcinoma including von Hippel-Lindau (VHL) syndrome, hereditary papillary renal carcinoma (HPRC), familial renal oncocytoma (FRO) associated with Birt-Hogg-Dube syndrome (BHDS), and hereditary renal carcinoma (HRC).

    Genetic studies are commonly used to classify renal cell tumors

    • Clear cell renal carcinoma
    • Papillary renal cell carcinoma
    • Chromophobe renal cell carcinoma
    • Collecting duct carcinoma

    Renal cell carcinoma is more common in people of Northern European ancestry (Scandinavians) and North Americans than in those of Asian or African descent. 

    Signs and Symptoms

    The classic triad of symptoms associated with a person with renal cell carcinoma is blood in the urine (hematuria), flank pain and an abdominal mass. This classic triad only occurs in 10-15% of people with advanced renal cell carcinoma, and now the majority of renal cell tumors are detected accidentally during CT or MRI imaging, usually for an unrelated causes.

    The most common signs at diagnosis include dark, rusty, or brown urine color due to blood in the urine (40% of cases), flank pain (40% cases), weight loss (33% of cases) anemia (30% of cases), abdominal mass (25% of cases). and high blood pressure (20% of cases). 

    Risk Factors for Renal Cell Carcinoma

    Risk factors for renal cell carcinomas can be divided into genetic, modifiable (preventable), and unavoidable causes.

    Genetic Risks for Renal Cell Carcinoma

    Renal cell carcinoma risk factors include a family history of the disease, and nearly 40% of patients with von Hippel-Lindau disease develop renal cell carcinoma. Also, people with the disease Tuberous sclerosis have a high probability of developing angiomyolipomas and renal cysts and can lead to renal cell carcinoma. 

    Unavoidable Risks for Renal Cell Carcinoma

    There is an increased incidence of acquired cystic disease of the kidney in patients undergoing long-term renal dialysis and subsequently predisposes to renal cell cancer.

    Modifiable Risks for Renal Cell Carcinoma

    Smoking tobacco 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 tobacco smoked in a dose-dependent fashion.

    Obesity is another risk factor, particularly in women; increasing body weight has a linear relationship with increasing risk.

    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, and phenacetin is often used as a cutting agent by illicit drug dealers to increase the size of samples of cocaine they intend to sell.

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