Renal Tumours
Benign Tumours
Renal Papillary Adenoma
- Small discrete adenomas arising from the renal tubular epithelium
- Found in 7-22% at post mortem
- Generally found in the cortex are discrete and are less that 20mm in diameter
- Microscopically they appear similar to renal cell carcinoma
- May metastasise
Renal Fibroma or Hamartoma (Renomedullary Interstitial Cell Tumour)
- Common small tumours found within the pyramids
- Microscopically they are composed of fibroblasts and collagenous tissue
- They have no malignant properties
Angiomyolipoma
- Benign tumour consisting of vessels, smooth muscle and fat
- Situated either in the cortex or medulla
- Are present in 25-50% of patients with tuberous sclerosis – a disease which is characterised by lesions of the cerebral cortex that produced epilepsy, mental retardation and variety of skin abnormalties
Oncocytoma
- Epithelial tumour composed of large cells which are granular with an eosinophilic cytoplasm and lots of mitochondria
- Thought to arise from the intercalated cells of the collecting ducts
- They are brownish, relatively homogenous and well capsulated but can get very large (up to 12cm)
- Benign
Malignant Tumours
Renal cell carcinoma
- Represents between 1-3% of all visceral cancers and 85% of all renal cancers
- Most often occurs between 60 and 80 and is 2 to 3 times more common in males
- They arise from the tubular epithelium and are therefore renal adenocarcinoma
Epidemiology
- Tobacco is the most significant risk factor
- Other risk factors;
- Obesity
- Hypertension
- Unopposed oestrogen therapy
- Exposure to asbestos, petroleum products and heavy metals
- Chronic renal failure
- Acquired cystic disease
- Tuberous sclerosis
- Obesity
- Mostly sporadic but unusual forms of autosomal dominant familial cancers occur. These include;
- Von Hippel-Lindau syndrome –
half to two thirds of VHL patients develop renal cysts and renal cell carcinoma. The VPL gene is implicated in the development of both hereditary and sporadic clear cell tumours - Hereditary clear cell carcinoma – confined to the kidney without the manifestations of VHL but with abnormalities involving the same or related gene
- Hereditary papilloma carcinoma – autosomal dominant. Characterised by multiple bilateral tumours with papillary origin. They exhibit mutations in the MET protooncogene
- Von Hippel-Lindau syndrome –
Classification of Renal cell carcinoma
1) Clear cell carcinoma
- Most common – 80% of cases
- Tumours are made up of cell with granular or clear cytoplasm and are nonpapillary
- 98% of tumours are associated with the VHL gene on the short arm of chromosome 3
- VHL acts as a tumour suppressor. It encodes part of a ubiquitin ligase complex involved in targeting proteins for degradation
- Two targets for VHL are HIF-1 and insulin-like growth factor 1. When upregulated these factors are involved in cell growth and angiogenesis
2) Papillary carcinoma
- Accounts for 10-15% of renal cancers
- It is associated with papillary growth
- Associated with the gene MET, a protooncogene which serves as the tyrosine kinase for hepatocyte growth factor (HGF). HGF is involved in growth, cell motility, invasion and differentiation
- Unlike clear cell carcinomas papillary carcinomas are frequently multifocal in origin
3) Chromophobe renal carcinoma
- Represents 5% of renal carcinomas
- Composed of cells with a prominent cell membrane, a pale eosinophilic nucleus usually surrounded by a halo
- Cytogenically these tumours exhibit multiple chromosome losses and extreme hypodiploidy
- They are though to derived from intercalated cells of the collecting ducts
- Have a better prognosis from clear cell and papillary carcinoma
4) Collecting duct carcinoma
- Represent around 1% of renal cancers
- Arises from the collecting duct cells of the medulla
- Histologically these tumours are characterised by nests of malignant cells enmeshed with a fibrotic stroma
- Form irregular channels lined by highly atypical epithelium with a hobnail pattern
Morphology
- Although tumours may arise anywhere most commonly they affect the upper pole
- Clear cell neoplasms arise from proximal tubular epithelium and form spherical masses of yellow(due to lipid accumulation)/grey material which can distort the renal outline. There may be areas of ischaemia, necrosis and haemorrhage
- Papillary tumours are though to arise from distal convoluted tubules and can be multifocal and bilateral. They can be large and are typically haemorrhagic and cystic. It is the most common renal cancer in patients who develop dialysis associated cystic disease
- Renal cell carcinoma may extend into the renal vein and grow as a solid column of cells within the vessel. This column may grow into the inferior vena cava and even into the right side of the heart
- Sarcomatoid changes can occur are an ominous feature
Clinical course
- The three classical diagnostic features of renal cell carcinoma are;
- Costovertebral pain
- Palpable mass
- Haematuria
- Costovertebral pain
- Renal cell carcinoma is classed as one of the ‘mimics’ of medicine because it produces diverse systemic symptoms. As well as fever and malaise it can also produce a number of paraneoplastic syndromes;
- Polycythaemia
- Hypercalcaemia
- Hypertension
- Hepatic dysfunction
- Feminisation or masculinisation
- Cushing syndrome
- Eosinophilia
- Amyloidosis
- Polycythaemia
- It has a tendency to metastasise before presenting with any signs
- 25% of patients presenting have metastases. Most common location of metastases;
- Lungs (50%)
- Bone (33%)
- Regional lymph nodes
- Liver
- Adrenal
- Brain
- Lungs (50%)
- 5 year survival rate is 45% or 70% in the absence of distant metastases
- With renal vein invasion or extension into the perirenal fat the figure is 15-20%
- Nephrectomy is the treatment of choice, either total or partial
Urothelial Carcinoma of the renal pelvis
- Approximately 5-10% of primary renal tumours arise from the urothelium of the renal pelvis
- These tumours span the range from benign papillomas to invasive urothelial (transitional cell) carcinoma
- Generally present quite early with haematuria
- Generally small when discovered
- May obstruct urinary outflow and lead to palpable hydronephrosis and flank pain
- Histologically they are the exact counterparts of transitional cell carcinoma of the bladder
- Urothelial tumours may be multiple involving the pelvis, ureters and bladder. In 50% of renal pelvic tumours there is a pre-existing bladder urothelial tumour
- There is an increased incidence of urothelial carcinoma in patients with analgesic nephropathy and is associated with analgesic abuse and exposure to aniline dyes
- Infiltration of the wall of the pelvis and calyces is common this is why the prognosis from these tumours is not good
- 5 year survival rate for low grade lesions is 50-70%. For high grade tumours it is 10%
Wilms Tumour
- The most common primary renal tumour of childhood and the fourth most common paediatric malignancy
- Incidence of 1 in 100,000 and is diagnosed between 2 and 5
- Males and females equally affected
- Derived from the primitive metanephros
- Approximately 5-10% of Wilms tumours occur bilaterally, either together or one after the other
- The onset of bilateral disease is approximately 10 months prior to disease of one kidney
Pathogenesis and genetics
- 90% of cases are sporadic
- About 15% of nonsyndromic patients with Wilms tumour demonstrate mutation in the WT1 tumour suppressor gene (Chr 11), that encodes a transcription factor expressed within the kidneys and gonads of the developing foetus
- Syndromes associated with mutations in WT1 (as well as other genes) include;
- WAGR syndrome – characterised by aniridia (lack of iris), genital anomalies, mental retardation and a 33% change of developing Wilms tumour. It is associated with a deletion of chromosome 11p3. Wilms tumour is due to a loss of WT1 and aniridia is due to a loss of PAX6
- Denys-Drash syndrome – characterised by gonadal dysgenesis and early onset nephropathy leading to renal failure. It is associated with a 90% chance of developing Wilms tumour. It is caused by a dominant negative mutation in the zinc finger domain of WT1, affecting its DNA binding properties. This affects the function of the WT allele yet this only causes genitourinary symptoms, for Wilms tumour to develop the WT allele must be inactivated
- Beckwith-Wiedemann syndrome - characterised by organomegaly, macroglossia, hemihypertrophy, omphalocele and adrenal cytomegaly. The locus that is involved is distal from the WT1 locus and is called WT2. Wilms tumour in these patients is associated with abherent methylation pattern, resulting in a loss of imprinting. In the locus the genes are normally only expressed from one parental allele, the other allele being silenced by hypermethylation. In Wilms disease this loss of imprinting results in increased expression of insulin-like growth factor-2 (IGF-2)
- WAGR syndrome – characterised by aniridia (lack of iris), genital anomalies, mental retardation and a 33% change of developing Wilms tumour. It is associated with a deletion of chromosome 11p3. Wilms tumour is due to a loss of WT1 and aniridia is due to a loss of PAX6
- In 15% of Wilms tumours there are b-catenin (involved in wnt signalling) mutations and there is a significant correlation between the presence of WT1 mutations and b-catenin mutations suggesting a synergistic role for these events in the development if Wilms tumour
Nephrogenic rests
- These are the putative precursor lesion in Wilms tumour
- Patients with nephrogenic nests are at increased risk of developing Wilms tumour in the contralateral kidney
- They may be hyperplastic or fibrotic
Morphology
- Tends to present as a large solitary, well-circumscribed mass
- On cut section the tumour is soft, homogenous, tan/grey with occasional foci of haemorrhage, cyst formation and necrosis
- Microscopically they are composed of three elements;
- Primitive small cell, blastematous tissue, resembling developing metanephric blastema
- Epithelial differentiation in the form of abortive tubules and glomeruli
- Stroma composed of spindle cells and striated muscle
- Primitive small cell, blastematous tissue, resembling developing metanephric blastema
Clinical features
- Present with large abdominal masses, haematuria, abdominal pain
- May also present with hypertension
- In a considerable number lung metastases are present at the time of presentation
- Prognosis is good with chemotherapy and nephrectomy – 2 year survival rate is 90%
- Some tumours can have anaplastic features and these display a poorer outcome