What are the types of renal tumours?
What is the malignant type we need to know all about?
Clear cell renal carcinoma (75% of tumours that arise)
Who gets Renal Cell Carcinoma most commonly?
50% more in men
Usually between 50 and 70 years of age
Risk factors: Smoking Hypertension Obesity Occupational exposure to toxins Genetic factors
Where do renal cell carcinomas come from?
The renal cortex
What does a tumour composed of clear cells look like under the microscope?
It is clear because cytoplasm is filled with carbohydrates and lipids and so the tumour looks yellow microscopically
What is Von Hippel-Lindau disease?
Disease in which people are unable to suppress tumours effectively due to a mutation in the VHL gene:
What happens to people with Von Hippel-Lindau disease?
People develop visceral cysts and tumours
Angiomas Haemangioblastomas Phaeochromocytomas Renal cell carcinoma Pancreatic cysts
What molecular mechanism causes sporadic clear cell RCC?
Loss of short arm of chromosome 3 either by deletion or unbalanced translocation and loss of one VHL gene.
Then other VHL gene undergoes mutation or hypermethylation
Which chromosome is the VHL gene on?
What happens when VHL is inactive?
IGF-1 is increased causing dysregulated cell growth.
IGF-1 upregulates hypoxia inducible factors which upregulate vascular endothelial growth factor (VEGF) and receptor causing new blood vessels to form
How do people present when they have RCC?
It was a silent cancer until very late in the disease.
Modern imaging means they often get picked up incidentally when other scans are being conducted
What are the classical symptoms of RCC?
Weight loss, fever, scrotal varices (Veins in the scrotum start to engorge)
Abdominal masses can be palpated in skinny patients and feels firm non-tender and moves with respiration
Costovertebratl angle pain
When does haematuria occur?
When the carcinoma invades the collecting system which means its pretty bad at that stage.
What is a potential complication with haematuria?
Clots can form that get stuck in the ureter which results in colicky pain
Why do scrotal varices occur?
IVC can be blocked by the carcinoma at the gonadal vein causing blood to pool at the scrotum.
This condition is very rare
What is renal cell carcinoma associated with? What other carcinoma is associated with this?
Small cell carcinoma of the lung can cause this to occur too
What are some paraneoplastic syndrome effects?
Hypercalcaemia (from overproduction of parathyroid hormone or metastasis to the bone)
Erythrocytosis (overproduction of erythropoietin)
Hypertension (overproduction of renin)
Cushing syndrome (overproduction of ACTH)
Other cytokines cause fever and weight loss
What is a common association between Renal Cell Carcinoma and veins?
As the carcinoma grows it gains access to the veins in the renal sinus which then goes to the IVC which makes it spread to lung, bone, and brain :(
What work is done when Renal Cell Carcinoma is suspected?
Bone scan if patient has bone pain
How is renal cell carcinoma staged?
On the basis of presence of absence of regional lymph node metastasis
M0 or M1 on the basis of presence or absence of distant metastasis
T1 or T2 is how big its getting and whether or not its accessed the veins of the renal sinus or IVC
T4 is when it invades into gerotas fascia
How is renal cell carcinoma treated typically?
Surgery as RCC is resistant to traditional chemotherapy and radiotherapy.
What are the types of therapies taking place at the moment?
Immunomodulatory therapies eg PD1 inhibitors and IL-2
Targeted therapies (block VEGF pathway)
Summary of RCC:
75% of cancers of the kidneys are clear cell renal cell carcinomas
Risk factors are smoking, obesity, and hypertension
Associated with inherited syndromes (VHL)
A silent cancer which may be present late or picked up incidentally
Classic triad: Haematuria, flank pain and palpable mass
Staged using the TNM system
What are the most common bladder tumours?
Urothelial carcinoma (90%)
Small percentage of them are squamous cell carcinomas
What is the previous name of urothelial carcinomas?
Transtional Cell Carcinoma
Where does the Urothelial / transitional cell carcinoma occur?
Anywhere in the urinary tract most common in the bladder
Clinically divided into superficial, muscle-invasive, and metastatic urothelial carcinomas
Who gets urothelial carcinomas?
Men more than women (3x)
What are the risk factors of bladder carcinoma?
Occupational carcinogen exposure (painters, rubber industry workers, textile industry workers, metal workers)
What part of the bladder does the urothelial bladder cell carcinoma occur?
What is the urothelium?
A multicellular tissue that is 3 - 7 cells thick and contains umbrella cell layer on surface to keep urine out of epithelium
What are the 2 pathways of urothelial cell carcinoma?
Flat pathway when malignant cells form a patch on the bladder surface.
Papillary pathway take supporting stroma and grow upward and outward and form cauliflower like bodies
What are the 2 types of bladder cancers>
P53 dependent (flat type and invade into bladder surface
P53 independent are low grade and less aggressive. They eventually lose P53 function and start metastasizing aggressively
What are the features of urothelial cell carcinoma?
They are multifocal and grow on several different cells at once and recurrent where they keep occuring repeatedly.
What are the 2 theories about the nature of urothelial cell carcinoma?
Field effect (Carcinogens acts on several cells of the bladder simultaneously)
Implantation theory (malignant cells float in urine and move from one place to another continuously
What are the symptoms of urothelial cell carcinomas?
Haematuria (must always be investigated)
No physical signs
What can be done to investigate urothelial cell carcinoma?
Urine cytology (urine analysis malignant cells looked for in urine)
Cytoscopy (taking image of the inside of the bladder
Imaging of the upper urinary tract (multifocal carcinoma)
If metastasis is suspected chest CT and bone scans
How is bladder cancer staged?
T1 into lamina propria
T2 into muscularis propria (deadly)
T3 paravesical fat
T4 adjacent organs
When is bladder cancer said to be deadly?
When it invades the detrusor muscle
What information does N staging use?
Absence or presence of nodal metastasis plus number of involved nodes (N0 to N3)
What does M indicate in staging?
Absence or presence of distant metastasis (M0 or M1)
How is urothelial carcinoma treated in non-muscle invasive urothelial carcinoma?
+/- local chemotherapy (attenuated version of tubercolosis used to fire up immune system)
How is urothelial carcinoma treated in muscle invasive carcinoma?
What is the incidence of squamous cell carcinoma?
less than 5% of bladder cancer in NA/Europe/Aus
In countries with schistosomiasis it is greater than 75% of bladder cancers (Egypt, South Africa, parts of Asia)
How do people get schistosomiasis?
They are located in water body which burrow through skin and they enter bladder which they irritate causing bladder cancer
What does squamous cell carcinoma look like?
Keratin layer around it is white and hard
Summary of bladder tumours
Usually urothelial carcinoma
More common in males
Cigarette smoking is a huge risk factor
Painless haematuria is a symptom
2 precursor lesions: Flat carcinoma and papillary urothelial carcinoma
TP53 and RB are central to development of muscle invasive urothelial carcinoma
Schistosomiasis infection is a risk factore for Squamous Cell Carcinoma