Introduction

This is an adenocarcinoma
These arise from the proximal tubular epithelium.
The tumours are highly vascular, and microscopically, they will appear as large cells with clear cytoplasm.
Haemorrhage within the kidney gives it a classic surface of mixed golden yellow with red.

Epidemiology

  • They are the most common renal carcinoma in adults.
  • They rarely present before the age of 40, and the average age of onset is 65-75
  •  Twice as common in men as women.

Aetiology

This is largely unknown, however some factors are suspected to precipitate this disease:

  • Irradiation
  • Exposure to oestrogens
  • Hypertension
  • Smoking
  • Exposure to cadmium
  • The disease is more commonly found in urban and industrial areas than in rural areas.
  • Incidence is 10 per 100 000 in males, and 5 per 100 000 in females.

Genetic Aspects

  • Rarely, the disease may run in families, in which case, there is a defect on chromosome 3p.
  • A similar defect is found in von Hippel-Lindau disease – an inherited condition where there are cysts and tumours of the kidney, pancreas, adrenal gland, epididymis, cerebellum and spinal cord. 2/3 of patients with this disease will develop renal carcinoma that is often bilateral and multifocal.
  • We can therefore deduce that it is the same tumour suppressor gene that is mutated in von Hippel-Lindau disease that is also implicated in the formation of renal cell carcinoma. Deletion of the short arm of chromosome 3 is a common finding in sporadic RCC. – remember that this deletion won’t cause von Hippel-Lindau disease because the disease is caused by an inherited mutation in every cell of the body, whereas in RCC, there will only be deletion of this segment in one renal cell, that then becomes cancerous.

Clinical Features

Often RCC is symptomless, until late stage. May be discovered incidentally.
The classic signs of this are:
  • Haematuria – 60%- this is caused by the spread of the tumour to the renal pelvis, which usually occurs very early on. From here it may spread to the renal vein and IVC.
  • Flank/loin pain (40%)
  • Palpable mass (25%)
    • These first three signs are the ‘classic’ ones, but actually only occur in 15% of patients.
  • Weight loss (30%)
  • Raised ESR
  • Polycythaemia (5%)
  • Hypertension (30%) – due to secretion of renin by the tumour
  • Anaemia (30%) – due to suppression of EPO by the tumour
  • Pyrexia of unknown origin (PUO) (20%)
  • Varicocoele (rare) – this occurs as a result of invasion of the left renal vein by the tumour, which may then affect drainage of blood from the testes.
However, many tumours are now discovered earlier as a result of incidental, or screening USS.
Note how some of these signs are endocrine effects caused by secretory activity of the tumour. These effects will disappear if the tumour is successfully treated, and if they do not, or they recur after treatment, they can be used as a marker for metastatic disease.

Invasion

  • Locally this is very common
  • Bone metastasis can occur anywhere in the body
  • Lymphatic spread it via the para-aortic nodes.

Diagnosis

  • USS – this will show any lumps on the kidney, and also lets you examine the renal vein and inferior vena cava (there may be signs of invasion). It allows you to differentiate between tumour and renal cyst.
  • Excretion urography – shows a space occupying lesion in the kidney, and in 10% of cases, it will be calcified.
    • Tumours of <3cm may be missed by both of these methods.
  • CT scan – will show similar things as USS, but can shows tumours as small as 1cm. About 50% of tumours less than 1cm in diameter will also be detected.
    • CT is also able to detect involvement of the renal vein and inferior vena cava – which are poor prognostic signs.
  • Raised ESR
  • Abnormal liver biochemistry – this will return to normal after successful treatment.
  • MRI – the most useful tool for tumour staging (better than CT).
  • LFTs are often abnormal, but will return to normal levels after surgery.
Staging is usually by the TNM scale. Treatment is determined by the stage of the tumour, as is survival. The basic investigations to asses the stage of the tumour are:
  • USS – to asses original tumour size (<3cm is said to be ‘small’)
  • MRI (perhaps with image guided biopsy) – will show lymphatic and venous involvement
  • Bone scan
Tumours of less than 3cm, without invasion of the lymphatic and venous tissue will have a 10 year survival rate of greater than 90%.

Treatment

The only way to treat these tumours is by surgical excision.
Usually, the treatment is total nephrectomy, however, in the case of bilateral disease, or a poorly functioning remaining kidney, then conservative surgery may be used. If there is just a small tumour on the outside of the kidney, then you can do ‘wedge surgery’ .
  • It is almost impossible for the surgeon to know what type of treatment will be needed until ‘they get in there’
As long as you have at least half of one fully functioning kidney, then renal function will be adequate.
During total nephrectomy, the perirenal fat and fascia will also be removed.
Even in the presence of metastasis, nephrectomy is still recommended, as in many cases there is regression of the metastasis after removal of the kidney.  In the case of a single metastasis, it is worthwhile to remove this secondary tumour as the metastasis is likely to be single due the relatively slow growing rate of renal cell carcinomas.

Advanced disease

  • For those with many metastasis, or invasion of the vena cava etc, then prognosis is generally very poor. Nephrectomy may still be performed to provide symptomatic relief, but most patients are unlikely to live longer than a year.
  • Medroxyprogesterone acetate may be useful in cases of metastatic disease.
  • Radiotherapy is only useful in treating bone mets.
  • Immunotherapy has been shown to be effective – treatment with interferon and interleukin-2 in patients with extensive disease is beneficial in 10-40% of cases, not necessarily ‘curing’ the disease, but it may prolong the patient’s life. In such cases, a nephrectomy will usually have been performed previously. Metastasis in the lungs are the most likely to respond to this sort of treatment.

Screening

There is no formal screening program. The disease is not very common, and has a wide range of presenting symptoms, and thus screening would not be cost effective.
The increasing use of USS of the abdominal for abdominal symptoms has meant a slight increase in the number of tumours identified early. 30% of tumours have metastasis at presentation.

Prognosis

5 year survival:

  • Tumours confined to kidney – 60-70%
  • Lymph node spread – 15-35%
  • Metastatic disease – 5%

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