25. Renal tumours (oncocytoma, renocellular cancer, Wilms tumor, urothelial carcinoma of the renal pelvis)

Many types of benign and malignant tumors occur in the urinary tract, however in the daily routine the most common ones are oncocytoma and renal cell carcinoma.

Benign renal tumours

Oncocytoma is the most important benign renal tumor. It originates from intercalated cells of the tubules. The name comes from the tumor cells are oncocytes, cells with large eosinophilic cytoplasm due to high content of mitochondria. The tumor is brownish on macroscopy. It can be hard to distinguish from chromophobe RCC, for which we must use cytogenetics.

Angiomyolipoma is a benign hamartoma of the kidney. It’s comprised of blood vessels, smooth muscle and adipose tissue, as the name suggests. It’s more frequent in patients with the systemic disease tuberous sclerosis.

Papillary adenoma is a small (5mm) and greyish benign tumor of the kidney.

Renal cell carcinoma

Renal cell carcinoma (RCC) is the most common histological type of kidney 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. Most are diagnosed with localised disease. Up to 70% of cases are incidentally diagnosed on imaging.

Malignancy of the renal pelvis is usually urothelial carcinoma and is therefore more similar to bladder cancer. It is not considered a renal cancer.

Risk factors

It's usually idiopathic, bue some risk factors are known:

• Smoking
• Cystic diseases of the kidney (polycystic kidney disease)
• Obesity
• Hypertension
• Hereditary RCC syndromes
  • von Hippel Lindau
  • Hereditary papillary RCC

Pathology

Renal cell carcinomas are adenocarcinomas which arise from the tubular epithelium. The most common types are clear cell carcinoma (80%+ of cases) and papillary carcinoma (10% of cases). Other types include:

• 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.

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.

Metastasis

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.

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.

Paraneoplastic syndromes

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
• Anaemia

Clinical features

Renal cell carcinoma may be asymptomatic in the initial stages, causing it to mostly be found incidentally. Up to 25% of cases already have distant metastases at diagnosis.

When symptomatic, 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

Non-dysmorphic haematuria, is usually present. There are no specific tumour markers.

Staging

The TNM staging of kidney tumors depend on the size, renal vein involvement and local invasion. 7 cm in size is the border between T1 and T2 tumours. Kidney tumors commonly infiltrate the fatty capsule and when they do they are T3. If they infiltrate beyond the renal fascia (Gerota fascia) the cancer is considered T4 and therefore inoperable.

Biopsy

Biopsi is often indicated, but is not necessary if the imaging findings are very typical for malignancy. If imaging cannot rule out benign tumour, biopsy is indicated.

Management

The main treatment for non-metastatic disease is surgical removal or resection of the kidney.

Wilms tumour

Wilms tumor or nephroblastoma is the most common malignant renal tumor in children; the average age the patient during diagnosis is 3 years old. It rarely occurs in adults, but it can happen. The tumor is comprised of blastema, the embryological tissue that the normal kidney develops from. This tumor may have primitive glomeruli and tubules.

Wilms tumor is associated with a mutation in the WT1 tumor suppressor, which especially occurs in case of WAGR syndrome.

Urothelial carcinoma can occur in the renal pelvis but it will be discussed in the next topic.