Bladder Neoplasms

Quick review of bladder structure:

Inside we find the ureter openings and trigone; inferior to it is the prostate.

It’s lined by transitional epithelium (like the ureters and urethra). Remember the layers, from bottom to top:

-         Basement membrane

-         Basal layer of cells

-         Multiple layers of urothelial cells (transitional epithelium cells)

-         Umbrella cells: the top layer of large cells with lots of cytoplasm. These help the bladder stretch and protect the organ from the toxic urine.

Basics about Urinary Bladder Tumors

·          50,000 new cases/year in the U.S., and 10,000 deaths/year. Found more in industrialized nations.

·          3X more prevalent in males. Bladder tumors usually occur between 50-80 years.

·          95% are epithelial in origin.

·          Risk factors:

-         smoking

-         exposure to arylamines (effects may kick in 40 years later)

-         long-term analgesic use

-         heavy long-term exposure to cyclophosphamide (causes hemorrhagic cystitis, too)

-         schistosoma haematobium, which is often found in Egypt. The eggs irritate the walls of the renal venous plexus, causing metaplasia à dysplasia à neoplasia (props to Alex S. for making us look bad in small group by knowing this).

Cytogenetic and molecular alterations in urinary bladder tumors

• Issues with chromosome 9 lead to loss of a tumor suppressor gene there
    - How? Chromosome 9 monosomy or deletions of 9p & 9q
• Loss of functional p53
    - How? Deletions of 17p includes p53 gene and mutation of p53.
• Loss of RB gene via 13q deletion.
• Deletions of 13p, 11p, & 14q.
• Increased expression of ras, c-myc and EGFR seen.

Testing for these tumors

• Urinalysis using in situ hybridization or probes for these chromosomes will reveal whether there are changes in the genes above, which indicates cancer growth.

Types of Urinary Bladder Tumors

These are all listed on a slide but not all were discussed.

•          Urothelial (TCC) tumors

–         Inverted papilloma

–         Papilloma (exophytic)

–         Urothelial tumors of low malignant potential (these are “between” benign and malignant—we can only determine which one they are based on their histology)

–         Urothelial carcinoma (low and high grade)

–         Carcinoma in situ

•          Squamous cell carcinoma

•          Mixed carcinoma

•          Adenocarcinoma

•          Small cell carcinoma (very aggressive!)

•          Sarcoma

What’s “in situ”?

• 95% of bladder tumors arise from the top layer of the epithelium (the mucosa).

• If they stay there, they are called “in situ”
  (or “non-infiltrating”). So tumors A and B are considered in situ.
• C and D, the invasive (“infiltrating”) forms, are not in situ.
  -  Superficial infiltrating tumors only reach the submucosa and top of the muscle.
  -  Deep infiltrating tumors reach the deep muscle, perivesical tissue, and lymphatic tissue.
     By the time tumors get here, 40% have metastasized to the lymph nodes.
• Note the difference between papillary (exophytic) and flat carcinoma.

OK now it gets better: some pictures of toomahs, and then a little on clinical stuff and staging.

 A. This is flat carcinoma in situ. Note the intact basement membrane (the tumor is only in the
     mucosa). This happens to be a malignant tumor. How do we know?

-         prominent pleomorphic nuclei

-         high nucleus: cytoplasm ratio

-         loss of polarity

Gross appearance of a hemorrhagic tumor in the posterior bladder wall (the trigone region). Note the irregular tumor that differs from the normal pale mucosa.
 

 B. This is papillary carcinoma. Remember that papillae have a fibrovascular core lined by neoplastic cells.

Papillary carcinomas can be exophytic (grow outwards) or grow into the bladder wall.
 

C. As stated above, superficial and deep infiltrating tumors reach the muscle layer (deep tumors get to the deep muscle)
 

D. Squamous cell carcinoma arises from squamous cells, not the urothelial epithelium (it’s obvious but your brain might be fried).

     -  Note the polygonal squamous cells and intercellular keratin bridges.     
     -  There’s a poor prognosis.

Clinical Course of Bladder Cancer

• Painless hematuria (initially microscopic, then macroscopic). Possible dysuria. Occasional frequency or urgency.
• 70% of tumors localize to the bladder
• Tumors expressing the A, B, H antigens have a better prognosis
   

 
Staging

Tumor characteristics (T in TNM) depend on how deep the tumor has grown and where it’s located. So Dr. Das included these two lists. Basically the deeper the tumor has grown, the farther beyond the original location it has spread.

•          T1- lamina propria

•          T2 - superficial muscularis propria

•          T3a - deep muscularis propria

•          T3b - perivesicle tissue

•          T4 - adjacent structures

•          T1 - Tumor <7cm, limited to kidney

•          T2 - Tumor >7cm, limited to kidney

•          T3 - Extends into major veins, adrenal gland, or perinephric tissue, but not beyond Gerota’s.

•          T4 - Tumor invades beyond Gerota’s fascia.

FINALLY - Some information on bladder inflammation, but the slides aren’t online. Here it is.

A. Acute and chronic cystitis

• Patient presents with frequency, pain, and dysuria.
• This can be caused be E.coli and other bacterial infection, viral, drugs, radiation.
• Can progress to pyelonephritis.

B. Interstitial cystitis

• More common in women
• Patient presents with dysuria
• Fissures (ulcers) in bladder mucosa lead to a fibrosed bladder wall. There may be some association with autoimmune diseases (which is why women have a higher incidence).
• There’s no specific treatment.

C. Malacoplakia

• Yellow plaque on bladder mucosa.
• Histo: Foamy histocytes with laminated concretions that stain purple. These concretions are calcified bacterial products (i.e., from E. coli or Proteus).

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