Module 4: Renal: Renal Cell Carcinoma, Bladder Cancer, cystitis

Question 1

Starting off will be Renal Cell Carcinoma, what is the pathogenesis for this?

Answer 1

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

Question 2

What is the origin for renal cell carcinoma?

Answer 2

Proximal tubule epithelial cells that arise from the cortex

Question 3

What are the pre-disposing factors for renal cell carcinoma sporadic?

Answer 3

HTN
Obesity 
Smoking 
Cadmium (batteries)
 Acquired polycystic kidney disease
B2 microglobulin 
--long standing dialysis

Question 4

There is also renal cell carcinoma that is inherited (5%) that is seen in younger adults. What is it associated with?

Answer 4

Bilateral and Multifocal

–associated with pheochromocytoma, cerebellar and retinal hemangioblastomas

Question 5

What are the three types of renal cell carcinoma?

Answer 5

Clear cells (most common): has glycogen and lipids
Papillary: has psammoma bodies
Chromophobe

Question 6

What is the classic triad of manifestations for patients with renal cell carcinoma?

Answer 6

Painless hematuria (no casts because the problem is in the kidney not below)
Flank Pain
Flank Mass

Question 7

What is the treatment for renal cell carcinoma?

Answer 7

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

Question 8

What is seen on histology for patients with clear cell renal carcinoma?

Answer 8

scanty stroma containing blood vessels and glycogen and lipids (Hence why its clear)

Question 9

What other diseases have a mutation in the VHL gene?

Answer 9

Renal Cell Carcinoma
Phenochromocytoma
Retinal and Cerebellar Hemangioblastomas

Question 10

What are complications associated with renal cell carcinoma?

Answer 10

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.

Question 11

What other carcinomas spread through the blood and not the lymph?

Answer 11

Renal Cell Carcinoma 
Choriocarcinoma 
Follicular Carcinoma 
Hepatocellular Carcinoma 
--liver, lung, brain, bone and kidneys

Question 12

Renal cell carcinoma also is responsible for paraneoplastic syndromes, which ones?

Answer 12

Renin: HTN
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)
Amyloidosis: AA

Question 13

Moving onto pathologies associated with the bladder. What is a diverticula in the bladder?

Answer 13

Pouch-like eversion/evagination of the bladder wall

Question 14

What is the congenital versus acquired pathogenesis for Diverticula?

Answer 14

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)

Question 15

What are complications seen with Diverticula?

Answer 15

Urine Stasis, infection, stone formation and carcinomas

Question 16

What is a urachus in regards to bladder pathology?

Answer 16

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

Question 17

Now moving onto cystitis, what are some features?

Answer 17

Occurs secondary to infection or radiation (hemorrhagic cystitis)

• -bacteria: E.coli, proteus, klebsiella, and enterobacter
• -fungus: Candida
• -parasites: S. hematobium

Question 18

What are pre-disposing factors to cystitis?

Answer 18

More common in females (short urethra)

• -DM
• -Instrumentation (catheter or cystoscopy)
• -bladder calculi
• -bladder outlet obstruction (BPH)

Question 19

What is the presentation for cystitis?

Answer 19

Urinary frequency 
Dysuria 
Suprapubic pain 
Fever 
Chilis 
Microhematuria

Question 20

There is also chronic interstitial cystitis which is common in middle aged females. What is seen on cystoscopic exam?

Answer 20

Edema, hemorrhage, ulceration of bladder mucosa

Question 21

What is seen on pathology of chronic interstitial cystitis?

Answer 21

Chronic inflammation (macrophages) and mast cells

Question 22

What is the presentation for cystitis?

Answer 22

Severe suprapubic pain, frequent/urgent urination, dysuria and hematuria

Question 23

The next big bladder pathology will focus on Bladder Cancer. What type is the most common?

Answer 23

Transitional or Urothelial Carcinoma

–also have adenocarcinoma and squamous

Question 24

What are the risk factors for transitional or urothelial carcinoma?

Answer 24

Smoking 
Analgesic abuse (phenacetin) 
Cyclophosphamide (immunosuppressant) 
Naphthylamine (Rubber factories) 
Mutations in p53, Rb and p16 
--more common in males

Question 25

What are the different types of transitional bladder cancer?

Answer 25

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

Question 26

How do all the bladder cancers present?

Answer 26

Painless hematuria Dysuria Urgency and Frequency Flank pain

Question 27

Now first lets talk about papillary urothelial carcinoma, what are some features?

Answer 27

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

Question 28

What is the histology seen for papillary urothelial carcinoma?

Answer 28

More than 5 layers with non-uniform layers --- if there is infiltration as seen on the image then this is invasive carcinoma

Question 29

Once papillary carcinoma becomes invasive what are features?

Answer 29

greater than 10 layers with atypica and invasion of fibrovascular core

Question 30

What are complications of invasive papillary carcinoma?

Answer 30

Obstruction --- back up of urine --- bilateral hydroureters/hydronephrosis -- chronic renal failure --- recurrent kidney and bladder stones/infections and acute urinary retention

Question 31

What is seen on the urine results for invasive papillary carcinoma?

Answer 31

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

Question 32

The second type of urothelial cancer is flat carcinoma and again it can be invasive and non invasive. What are some features?

Answer 32

High Grade Tumor Presents late Poor prognosis b/c it invades bladder wall --most invasive flat come from non invasive not de novo.

Question 33

How is a diagnosis made of flat or papillary carcinoma?

Answer 33

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)

Question 34

Now very briefly, when do you see patients with squamous bladder cancer?

Answer 34

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

Question 35

Now again very briefly, when do you see patients with adenocarcinoma of the bladder?

Answer 35

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

Question 36

What is more common mets to the bladder or primary bladder cancer?

Answer 36

Mets to the bladder is more common than primary bladder cancer