Renal cell carcinoma (RCC, also known as hypernephroma) is a kidney cancer that originates in the lining of the proximal renal tubule, the very small tubes in the kidney that filter the blood and remove waste products. RCC is the most common type of kidney cancer, and the most common type in adults, responsible for approximately 80% of cases.. Initial treatment is most commonly a radical or partial nephrectomy and remains the mainstay of curative treatment. Where the tumour is confined to the
renal parenchyma, the 5-year survival rate is 60-70%, but this is lowered considerably where metastases have spread. It is resistant to radiation therapy and chemotherapy, although some cases respond to immunotherapy. Targeted cancer therapies such as sunitinib, temsirolimus, bevacizumab, interferon-alpha, and possibly sorafenib have improved the outlook for RCC (progression-free survival), although they have not yet demonstrated improved survival.

Signs and symptoms

The classic triad is hematuria (blood in the urine), flank pain and an abdominal mass. This is now known as the 'too late triad' because by the time patients present with symptoms, their disease is often advanced beyond a curative stage. In addition, whilst this triad is highly suggestive of RCC, it only occurs in around 15% of the sufferers. Today, the majority of renal tumors are asymptomatic and are detected incidentally on imaging, usually for an unrelated cause.

Signs may include:

• Abnormal urine color (dark, rusty, or brown) due to blood in the urine (found in 60% of cases)
• Loin pain (found in 40% of cases)
• Abdominal mass (25% of cases)
• Malaise, weight loss or anorexia (30% of cases)
• Polycythemia (5% of cases)
• Anaemia resulting from depression of erythropoietin (5% of cases)
• The presenting symptom may be due to metastatic disease, such as a pathologic fracture of the hip due to a metastasis to the bone
• Varicocele, the enlargement of one testicle, usually on the left (2% of cases). This is due to blockage of the left testicular vein by tumor invasion of the left renal vein; this typically does not occur on the right as the right gonadal vein drains directly into the inferior vena cava.
• Vision abnormalities
• Pallor or plethora
• Hirsutism - Excessive hair growth (females)
• Constipation
• Hypertension (high blood pressure) resulting from secretion of renin by the tumour (30% of cases)
• Elevated calcium levels (Hypercalcemia)
• Paraneoplastic disease

Classification

Recent genetic studies have altered the approaches used in classifying renal cell carcinoma. The following system can be used to classify these tumors:

• Clear cell carcinoma (VHL and others on chromosome 3)
• Papillary carcinoma (MET, PRCC)
• Chromophobe renal carcinoma
• Collecting duct carcinoma

Other associated genes include TRC8, OGG1, HNF1A, HNF1B, TFE3, RCCP3, and RCC17.