Renal cell carcinoma - Genitourinary oncology

Renal cell carcinoma

Definition

Adenocarcinoma of the kidney, which arises from the renal tubular epithelium. (Previously also called hyper-nephroma or Grawitz tumour).

Prevalence

2% of all visceral tumours; 85–90% of primary renal malignancies in adults.

Age

Increases with age, most over age 50 years.

Sex

M > F (3:1)

Aetiology

Predisposing factors include smoking, carcinogens such as asbestos and petrochemical products, obesity and genetic factors.

In von Hippel–Lindau (vHL) syndrome (an autosomal dominant inherited condition with familial haemangioblastomas in the CNS) one third of patients develop clear cell renal cell carcinoma (CCRCC). In tuberose sclerosis, most renal lesions are benign angiomyolipomas, but there is also an increased risk of papillary renal cell carcinoma.

Pathophysiology

The VHL gene is a tumour suppressor gene. More than 75% of sporadic CCRCC have loss of or inactivation of both VHL alleles.

Papillary renal cell tumours may have trisomy of Chr 17 (adenomas) or with additional trisomy of 16, 20 or 12 (carcinomas).

Clinical features

Presenting symptoms may include haematuria, fever, night sweats, anorexia, abdominal or loin mass, loin pain and weight loss. Systemic features or paraneoplastic syndromes are relatively common:

·        A normochromic, normocytic anaemia is common, but polycythaemia, i.e. increased red cell mass, occurs in up to 5% of patients, due to the overproduction of erythropoietin.

·        Hypercalcaemia is common, either due to bony metastases or the production of parathyroid hormone-related protein (PTHrP).

·        Polymyalgia-like symptoms with aching proximal muscles may occur, which are unresponsive to steroid therapy.

Many patients remain asymptomatic until advanced local disease or metastases develop, so may present with the symptoms of complications and increasingly lesions are diagnosed incidentally.

On examination, occasionally a palpable loin mass may be found and lymphadenopathy, hepatosplenomegaly, ascites, a varicocele (which does not collapse when supine) in the scrotal sac and any evidence of metastases should be looked for.

Other features which may raise the suspicion of renal cell carcinoma include hypertension, raised ESR, or abnormal liver function tests despite a lack of liver metastases.

Macroscopy

There is a rounded mass, usually in the upper pole, with a soft, yellow-grey cut surface with haemorrhage and necrosis. It is often surrounded by a pseudocapsule.

Microscopy

Sheets of clear or granular cells with small or normal looking nuclei and cytoplasmic glycogen or fat. They are similar in appearance to adrenal cortical cells, hence ‘hypernephroma’. Different histological subtypes have been described, the most common of which are clear cell (75–85%) and papillary/chromophilic (15%).

Complications

Local spread especially into the renal vein, and may grow as far as the inferior vena cava and right atrium. Tumour may also spread into neighbouring tissues, such as the adrenal gland and other abdominal organs. Lymphatic spread is common. Distant spread occurs as cannonball metastases in bone, lungs, brain or liver.

Investigations

Urinalysis shows haematuria in âˆ¼40%. Blood tests including FBC, U&Es, ESR, LFTs and calcium.

Renal ultrasound scan is usually the diagnostic imaging method. A solid tumour >3 cm is diagnostic, but sometimes a cyst is seen which needs to be differentiated between a simple benign cyst, a complex cyst or solid tumour. Doppler USS should be performed to look for renal vein thrombus.

Abdominal CT scan will show in more detail any suspicious features: thickened, irregular walls, multiloculated mass and contrast enhancement. CT will also demonstrate any local invasion, lymph node and renal vein involvement.

Staging tests include chest X-ray and CT chest, bone scan.

Management

Surgical removal is the treatment of choice for those without metastases (if there is a single metastasis this can be resected along with the primary tumour). The tumour is very resistant to chemotherapy or radiotherapy. In the past, radical nephrectomy with removal of the kidney, perinephric fact, together with the ipsilateral adrenal gland and hilar and paraaortic lymph nodes was routinely performed. Some now perform either total nephrectomy (without removal of the adrenal or lymph nodes), or more conservative surgery, i.e. wide resection or partial nephrectomy, for tumours <5 cm in size, but these techniques may have a greater risk of recurrence.

Palliative radiotherapy is used for symptomatic painful bone or skin metastases.

Highly vascular metastases, e.g. in lung or bone may cause pain or haemorrhage which can be treated effectively by local arterial embolisation.

Hormonal therapy and immunotherapy are being investigated on a trial basis.

Prognosis

If confined to renal capsule 10-year survival is 70%. Very poor if metastases present, 25% of patients present with metastases and they have a 45% 5-year survival.