Flashcards in Module 4: Renal: Renal Cell Carcinoma, Bladder Cancer, cystitis Deck (36):
Starting off will be Renal Cell Carcinoma, what is the pathogenesis for this?
Mutation of VHL (von-hippel lindau) tumor supressor gene (3p)
--more common in older men 60-70
--unilateral and unifocal for sporadic and bilateral and multifocal for inherited
What is the origin for renal cell carcinoma?
Proximal tubule epithelial cells that arise from the cortex
What are the pre-disposing factors for renal cell carcinoma sporadic?
Acquired polycystic kidney disease
--long standing dialysis
There is also renal cell carcinoma that is inherited (5%) that is seen in younger adults. What is it associated with?
Bilateral and Multifocal
--associated with pheochromocytoma, cerebellar and retinal hemangioblastomas
What are the three types of renal cell carcinoma?
Clear cells (most common): has glycogen and lipids
Papillary: has psammoma bodies
What is the classic triad of manifestations for patients with renal cell carcinoma?
Painless hematuria (no casts because the problem is in the kidney not below)
What is the treatment for renal cell carcinoma?
Subtotal nephrectomy (excisional biopsy)
--urine cytology not good
Dont take incisional biopsy because you can spread it in the blood
--dx can be confirmed by renal ultrasound scan --- bilateral shrunken kidneys
What is seen on histology for patients with clear cell renal carcinoma?
scanty stroma containing blood vessels and glycogen and lipids (Hence why its clear)
What other diseases have a mutation in the VHL gene?
Renal Cell Carcinoma
Retinal and Cerebellar Hemangioblastomas
What are complications associated with renal cell carcinoma?
Hematogenous spread: lungs (cannonball lesions), brain and bones (lytic lesions)
--does not spread through lymph (Exception)
FSGS from subtotal nephrectomy: due to compensatory hyperfiltration by the other kidney now.
What other carcinomas spread through the blood and not the lymph?
Renal Cell Carcinoma
--liver, lung, brain, bone and kidneys
Renal cell carcinoma also is responsible for paraneoplastic syndromes, which ones?
EPO: polycythemia (high EPO does not allow for negative feedback)
ACTH: cushing's syndrome
PTH-like peptide: Hypercalcemia
Leukamoid Reaction: neutrophilia (elevated LAP score--unlike CML with normal LAP score)
Moving onto pathologies associated with the bladder. What is a diverticula in the bladder?
Pouch-like eversion/evagination of the bladder wall
What is the congenital versus acquired pathogenesis for Diverticula?
Congenital: due to defect in development of muscle wall of the bladder
Acquired: due to increased intravesical pressure secondary to obstruction to urine outflow (BPH)
What are complications seen with Diverticula?
Urine Stasis, infection, stone formation and carcinomas
What is a urachus in regards to bladder pathology?
Persistent tubular structure
--between bladder and umbilicus
--fibrosis of the cord is basically formed
--if not surgically excised patients can pee out of the belly button and patients have an increased risk for adenocarcinoma
Now moving onto cystitis, what are some features?
Occurs secondary to infection or radiation (hemorrhagic cystitis)
--bacteria: E.coli, proteus, klebsiella, and enterobacter
--parasites: S. hematobium
What are pre-disposing factors to cystitis?
More common in females (short urethra)
--Instrumentation (catheter or cystoscopy)
--bladder outlet obstruction (BPH)
What is the presentation for cystitis?
There is also chronic interstitial cystitis which is common in middle aged females. What is seen on cystoscopic exam?
Edema, hemorrhage, ulceration of bladder mucosa
What is seen on pathology of chronic interstitial cystitis?
Chronic inflammation (macrophages) and mast cells
What is the presentation for cystitis?
Severe suprapubic pain, frequent/urgent urination, dysuria and hematuria
The next big bladder pathology will focus on Bladder Cancer. What type is the most common?
Transitional or Urothelial Carcinoma
--also have adenocarcinoma and squamous
What are the risk factors for transitional or urothelial carcinoma?
Analgesic abuse (phenacetin)
Naphthylamine (Rubber factories)
Mutations in p53, Rb and p16
--more common in males
What are the different types of transitional bladder cancer?
Papillary carcinoma or invasive papillary carcinoma (invades the actual bladder )
Flat non invasive carcinoma (carcinoma in situ) and flat invasive carcinoma (invasion into the bladder)
--most invasive flat comes from the non invasive flat carcinoma
How do all the bladder cancers present?
Urgency and Frequency
Now first lets talk about papillary urothelial carcinoma, what are some features?
Note 1a and 1b
Projects into lumen of the bladder and causes obstructive symptoms so patient presents early --- better prognosis
--much more common
--exophytic, multifocal, low grade with a high chance of recurrence
More common, more likely to re-occur after surgery and more likely to cause hydroureter/hydronephrosis
What is the histology seen for papillary urothelial carcinoma?
More than 5 layers with non-uniform layers --- if there is infiltration as seen on the image then this is invasive carcinoma
Once papillary carcinoma becomes invasive what are features?
greater than 10 layers with atypica and invasion of fibrovascular core
What are complications of invasive papillary carcinoma?
Obstruction --- back up of urine --- bilateral hydroureters/hydronephrosis -- chronic renal failure --- recurrent kidney and bladder stones/infections and acute urinary retention
What is seen on the urine results for invasive papillary carcinoma?
Two casts: WBC (Acute pyelonephritis) and waxy (chronic renal failure)
--patients also get iron deficiency anemia due to the painless hematuria
RBC without casts because its below the kidney
The second type of urothelial cancer is flat carcinoma and again it can be invasive and non invasive. What are some features?
High Grade Tumor
Poor prognosis b/c it invades bladder wall
--most invasive flat come from non invasive not de novo.
How is a diagnosis made of flat or papillary carcinoma?
Cystoscopy and biopsy most accurate test
--atypical epithelial cells and multilayering
--flat is worse because it can invade the bladder wall
--papillary is more likely to cause bilateral hydronephrosis (also more likely to recur following resection)
Now very briefly, when do you see patients with squamous bladder cancer?
Only seen in Egyptian Immigrants
--S. hematobium: causes squamous dysplasia, squamous carcinoma and keratin pearls
---has to be purely squamous
Also seen in patients with bladder stones
Now again very briefly, when do you see patients with adenocarcinoma of the bladder?
Associated with bladder urachus (persistence of a cystic structure from umbilicus to the dome of the bladder)
--glandular dysplasia -- adenocarcinoma --malignant glands invading the bladder wall
--has to be purely adenocarcinoma