Bladder cancer pathophysiology

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Steven C. Campbell, M.D., Ph.D.

Overview

Genes involved in the pathogenesis of bladder cancer include HRAS, Rb1, PTEN/MMAC1, NAT2, and GSTM1.

Pathogenesis

• Under normal conditions, the bladder, the lower part of the kidneys (the renal pelvises), the ureters, and the proximal urethra are lined with a specialized mucous membrane referred to as transitional epithelium (also called urothelium).
• Most cancers that form in the bladder, the renal pelvises, the ureters, and the proximal urethra are transitional cell carcinomas (also called urothelial carcinomas) that derive from transitional epithelium.
• Urothelial carcinomas may be non-invasive (only in the lining of the bladder) or invasive (growing into other layers of the bladder wall).

Genetics

Genetic mutations:

• HRAS mutation
• Rb1 mutation
• PTEN/MMAC1 mutation
• NAT2 slow acetylator phenotype
• GSTM1 null phenotype

Gross Pathology

• Non-invasive urothelial carcinoma

• On gross pathology, flat lesions or papillary lesions are characteristic findings of non-invasive urothelial carcinoma.

• Invasive urothelial carcinoma

Microscopic Pathology

• Non-invasive urothelial carcinoma

• Flat lesions

• On microscopic histopathological analysis, loss of cell polarity, nuclear crowding, and nuclear crowding are characteristic findings.

• Papillary lesions

• On microscopic histopathological analysis, fibrovascular stalks, umbrella cells, and eosinophilic cytoplasm are characteristic findings.

• Invasive urothelial carcinoma