What causes squamous cell carcinoma of the urinary bladder?

Answer

Keratinous squamous metaplasia has been associated with an increased risk of developing squamous cell carcinoma, with approximately one half of the cases arising subsequent to the metaplasia.^{[3, 11, 12]}The majority of cases arise in the context of chronic cystitis.^[13]Chronic irritation secondary to lithiasis,^{[1, 2]}urinary retention, and indwelling catheters has also been linked to the development of squamous cell bladder carcinoma.^[2]

Having bladder diverticula may increase the likelihood that an individual will develop squamous cell carcinoma.^[14]Bladder exstrophy has been associated with the development of squamous cell carcinoma at a younger age than usual.^{[15, 16, 17, 18]}Squamous cell carcinoma may arise in a urachal remnant.^{[19, 20, 21, 22, 23]}

Smoking has a well-recognized role in the development of bladder carcinoma, with smoking duration and intensity directly related to an increased risk.^{[24, 25, 26]}The risk of developing bladder carcinoma is two to six times higher in smokers than in nonsmokers. Cyclophosphamide chemotherapy has also been reported to increase the incidence of squamous cell carcinoma of the bladder.^[27]Rarely, bacillus Calmette-Guérin (BCG) treatment for carcinoma in situ has been reported to lead to development of squamous cell carcinoma.^[28]

As previously mentioned, schistosomiasis is the major cause of squamous cell carcinoma of the bladder in African countries. Its pathogenetic role is well studied. In one study from Egypt, 82% of patients with bladder carcinoma were found to harbor Schistosoma haematobium eggs in the bladder wall.^[29]The presence of eggs was associated with the development of cancer at a younger age and with a predominance of squamous cell carcinoma, relative to egg-negative cases. A higher degree of adenocarcinoma has also been reported in schistosomal-associated bladder carcinomas.^[29]

Three pathogenic species responsible for the disease in humans are S haematobium, S mansoni, and S japonicum. The eggs reside in the pelvic and mesenteric venous plexus. In the bladder, the deposition of Schistosoma eggs commonly provokes a severe inflammatory response and fibrosis.

The eggs are found embedded in the lamina propria and muscularis propria of the bladder wall; many of the eggs are destroyed by host reaction and become calcified. This results in a granular, yellow-tan surface lesion commonly known as a sandy patch. S haematobium total antigen has been reported to increase proliferation, migration, and invasion of Schistosoma and to decrease apoptosis of normal epithelial cells.^[30]

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Pathology of of urinary bladder squamous cell carcinoma. This image shows a cross-section through the bladder, uterus, and vagina with squamous cell carcinoma of the bladder infiltrating through the bladder wall into the vaginal wall.
Pathology of of urinary bladder squamous cell carcinoma. This histologic image reveals deeply infiltrated, moderately differentiated squamous cell carcinoma of the bladder.
Pathology of of urinary bladder squamous cell carcinoma.Note the infiltration into the muscularis propria by small nests and individual tumor cells.
Pathology of of urinary bladder squamous cell carcinoma. This image shows squamous carcinoma in situ adjacent to the tumor.

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