Tumour

Renal Cell Carcinoma

RCC

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Renal cell carcinoma (RCC) is a kidney cancer that originates in the lining of the proximal convoluted tubule, a part of the very small tubes in the kidney that transport waste molecules from the blood to the urine. RCC is the most common type of kidney cancer in adults, responsible for approximately 90–95% of cases.

Initial treatment is most commonly either partial or complete removal of the affected kidney(s). Where the cancer has not metastasised (spread to other organs) or burrowed deeper into the tissues of the kidney, the 5-year survival rate is 65–90%, but this is lowered considerably when the cancer has spread.

The body is remarkably good at hiding the symptoms and as a result people with RCC often have advanced disease by the time it is discovered. The initial symptoms of RCC often include: blood in the urine (occurring in 40% of affected persons at the time they first seek medical attention), flank pain (40%), a mass in the abdomen or flank (25%), weight loss (33%), fever (20%), high blood pressure (20%), night sweats and generally feeling unwell. When RCC metastasises, it most commonly spreads to the lymph nodes, lungs, liver, adrenal glands, brain or bones. Immunotherapy and targeted therapy have improved the outlook for metastatic RCC.

RCC is also associated with a number of paraneoplastic syndromes (PNS) which are conditions caused by either the hormones produced by the tumour or by the body’s attack on the tumour and are present in about 20% of those with RCC. These syndromes most commonly affect tissues which have not been invaded by the cancer. The most common PNSs seen in people with RCC are: high blood calcium levels, polycythaemia (the opposite of anaemia, due to an overproduction of erythropoietin), thrombocytosis (too many platelets in the blood, leading to an increased tendency for blood clotting and bleeds) and secondary amyloidosis.

Signs and symptoms

Historically, medical practitioners expected a person to present with three findings. This classic triad is

1: haematuria, which is when there is blood present in the urine,

2: flank pain, which is pain on the side of the body between the hip and ribs, and

3: an abdominal mass, similar to bloating but larger.

It is now known that this classic triad of symptoms only occurs in 10–15% of cases, and is usually indicative that the renal cell carcinoma (RCC) in an advanced stage. Today, RCC is often asymptomatic (meaning little to no symptoms) and is generally detected incidentally when a person is being examined for other ailments.

Other signs and symptom may include haematuria; loin pain; abdominal mass; malaise, which is a general feeling of feeling unwell; weight loss and/or loss of appetite; anaemia resulting from depression of erythropoietin; erythrocytosis (increased production of red blood cells) due to increased erythropoietin secretion; varicocele, which is seen in males as an enlargement of the pampiniform plexus of veins draining the testis (more often the left testis) hypertension (high blood pressure) resulting from secretion of renin by the tumour; hypercalcemia, which is elevation of calcium levels in the blood; sleep disturbance or night sweats; recurrent fevers; and chronic fatigue.

Cause

Lifestyle

The greatest risk factors for RCC are lifestyle-related; smoking, obesity and hypertension (high blood pressure) have been estimated to account for up to 50% of cases. Occupational exposure to some chemicals such as asbestos, cadmium, lead, chlorinated solvents, petrochemicals and PAH (polycyclic aromatic hydrocarbon) has been examined by multiple studies with inconclusive results. Another suspected risk factor is the long term use of non-steroidal anti-inflammatory drugs (NSAIDS).

Finally, studies have found that women who have had a hysterectomy are at more than double the risk of developing RCC than those who have not. The reason for this remains unclear.

 

Genetics

papillary renal carcinoma, hereditary leiomyomatosis, Birt-Hogg-Dube syndrome, hyperparathyroidism-jaw tumor syndrome, familial papillary thyroid carcinoma, von Hippel-Lindau disease and sickle cell disease.

The most significant disease affecting risk however is not genetically linked – patients with acquired cystic disease of the kidney requiring dialysis are 30 times more likely than the general population to develop RCC.

 

Pathophysiology

The tumour arises from the cells of the proximal renal tubular epithelium. It is considered an adenocarcinoma. There are two subtypes: sporadic (that is, non-hereditary) and hereditary. Both such subtypes are associated with mutations in the short-arm of chromosome 3, with the implicated genes being either tumour suppressor genes (VHL and TSC) or oncogenes (like c-Met).

Diagnosis

The first steps taken to diagnose this condition are consideration of the signs and symptoms, and a medical history (the detailed medical review of past health state) to evaluate any risk factors. Based on the symptoms presented, a range of biochemical tests (using blood and/or urine samples) may also be considered as part of the screening process to provide sufficient quantitative analysis of any differences in electrolytes, renal and liver function, and blood clotting times. Upon physical examination, palpation of the abdomen may reveal the presence of a mass or an organ enlargement.

Although this disease lacks characterization in the early stages of tumor development, considerations based on diverse clinical manifestations, as well as resistance to radiation and chemotherapy are important. The main diagnostic tools for detecting renal cell carcinoma are ultrasound, computed tomography (CT) scanning and magnetic resonance imaging (MRI) of the kidneys.

 

Classification

Renal cell carcinoma (RCC) is not a single entity, but rather a collection of different types of tumours, each derived from the various parts of the nephron (epithelium or renal tubules) and possessing distinct genetic characteristics, histological features, and, to some extent, clinical phenotypes.

Source: Wikipedia