Renal cell carcinoma

Renal cell carcinoma (RCC) is the most common renal cancer in adults, accounting for 80+%. It's a malignant epithelial tumor that arises from the kidney tubules. It's usually discovered incidentally. When symptomatic, it usually presents with a classic triad of haematuria (with normal and not dysmorphic RBCs), costovertebral pain and/or a palpable mass in the flank.

It's a relatively rare malignancy, with an incidence of 15/100 000 new cases every year. It's mostly a disease of elderly men.

Etiology

The most important risk factors for RCC are:

• Smoking
• Cystic diseases of the kidney (polycystic kidney disease)
• Obesity
• Hypertension

Pathology

As RCC commonly grows to the renal vein and IVC is metastasis to the lungs and bone most frequent. The tumor grows as a solid column inside the renal vein, sometimes extending as far as the IVC or the heart. As for lymph nodes it first spreads to retroperitoneal lymph nodes.

Staging and grading

The Furhman system is used as grading system for kidney tumors. It’s based mostly on how prominent the nucleoli are – the more prominent, the higher the grade. A grade IV RCC has sarcomatoid or rhabdoid appearance.

The TNM staging of kidney tumors depend on the size, renal vein involvement and local invasion. Kidney tumors commonly infiltrate the fatty capsule, which is T3. If they infiltrate beyond the renal fascia (Gerota fascia) is the cancer considered T4 and therefore inoperable.

Histological types

There are different types of RCC according to the histology:

• Clear cell RCC or conventional RCC – 65% of cases
• Papillary RCC – 10% of cases
• Chromophobe RCC – 5% of cases
• Cystic RCC – 2.5% of cases
• Collecting duct RCC – 1% of cases

Clear cell RCC gets its name from the clear cytoplasm of the tumor cells that is visible on histology. This is due to the tumor cells’ high fat content, which also makes the tumor yellow on macroscopy. Clear cell RCC can have capsule and be well-demarcated, so it can mimic the morphology of a benign tumor. It typically occurs in the lower pole. Clear cell RCC has worse prognosis than the next two subtypes.

Loss of the tumor suppressor VHL on chromosome 3p25 is involved in clear cell RCC, either sporadic or hereditary as is the case in von Hippel-Lindau disease. 50% of people with this disease develop clear cell RCC. VHL-disease related clear cell RCC usually occurs as multiple and bilateral tumors.

Papillary RCC gets its name from the papillary growth pattern it shows. These tumors appear in multiple foci and bilaterally. The MET proto-oncogene on chromosome 7q31 is associated with papillary RCC, both in hereditary and sporadic forms.

Chromophobe RCC gets its name from the chromophobe histology, i.e. the tumor cells stain darkly. The tumor cells have usually lost multiple chromosomes, making them hypoploid. This type has good prognosis.

Cystic RCC is a rare type of RCC that is commonly misdiagnosed as a benign renal cyst. It has an excellent prognosis after surgical removal.

Collecting duct RCC is a very rare subtype. It’s very aggressive and has a particularly bad prognosis.

Clinical features

Renal cell carcinoma may be asymptomatic in the initial stages, causing it to be a very frequent incidental finding. Up to 25% of cases already have distant metastases at diagnosis.

Renal cell carcinoma has a typical triad of symptoms:

• Haematuria (with normal and not dysmorphic RBCs)
• Costovertebral pain
• Palpable mass in the flank

..., however it's rare for RCC to present with the triad. It may also cause non-specific symptoms like fever and weight loss.

Diagnosis and evaluation

Haematuria, especially dysmorphic haematuria, is usually present.

Imaging

CT with contrast is required to make the diagnosis, but ultrasound is sometimes the first imaging modality used. Ultrasound may show an expanding hyperechoic or hypoechoic process. On CT renal cell carcinoma is visible as the tumour enhances with contrast. Invasion of the renal vein is common.

Management

The main treatment is surgery.

Complications

RCC can cause various paraneoplastic syndromes:

• Hypertension – as it can produce renin
• Hypercalcaemia – as it can produce parathyroid hormone-related protein (PTHrP)
• Polycythaemia – as it can produce EPO
• Secondary hypercortisolism (Cushing syndrome) – as it can produce ACTH

RCC can also cause a left-sided varicocele, a pathological dilation of the venous plexus of the scrotum. This tumor commonly spreads locally to the renal vein, where it can block the point the left testicular vein drains into the renal vein. This blockage causes pressure to build up in the venous plexus of the scrotum which may be felt as a soft lump.

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