Non-urothelial bladder cancers

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Non-urothelial bladder cancers

Renal system


Non-urothelial bladder cancers


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Non-urothelial bladder cancers

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A 20-year-old man comes to the clinic due to burning urination for the past 3 weeks. The patient recently returned from a trip to Egypt, where he hiked and swam in freshwater. During that time, the patient developed an itchy rash over some parts of the body, which self-resolved after a few days. Medical history is unremarkable besides a gonorrhea infection 3 years ago, which was successfully treated with antibiotics. Vital signs are within normal limits. Physical examination shows no abnormalities. Complete blood count shows:  
 Laboratory value  Result 
 Hemoglobin  12 g/dL 
 Hematocrit  40% 
 Leukocyte count  12,100/mm3 
 Platelet count  400,000/mm3 
 Leukocyte count  16000/mm3 
 Neutrophils, segmented  54% 
 Neutrophils, banded  5% 
 Eosinophils  12% 
 Basophils  0% 
 Lymphocytes  25% 
 Monocytes  7% 
Urine sample is obtained and the specimen under light microscopy is shown below:    

Reproduced from: Wikimedia Commons  
If left untreated, this patient is most likely to develop which of the following complications?  

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Bladder cancer

cisplatin/carboplatin for p. 448

hematuria, with p. 618

hypercalcemia and p. 221

oncogenic microbes and p. 224

Schistosoma haematobium p. , 158, 158

Hematuria p. 620

bladder cancer p. 624

Schistosoma haematobium

bladder cancer p. 224


There are two types of bladder cancers—urothelial and non-urothelial types.

The urothelium is special type of transitional cell epithelium that forms a stretchy, protective barrier in the bladder. The majority of primary bladder tumors are urothelial cell carcinomas also known as transitional cell carcinomas that obviously originate from the urothelium.

Somewhat confusingly, non-urothelial tumors, like squamous cell carcinomas and adenocarcinomas, also often arise from the urothelium layer but are distinguished by the way that their cells differentiate.

For example, the normal bladder surface is not normally lined with squamous epithelium, yet the cells in the urothelium can change shape and take on a flat, pancake-like appearance of squamous cells. This non-cancerous change is called squamous cell metaplasia.

If these cells begin to grow unchecked they can turn into a squamous cell carcinoma. These tumors typically pop up in multiple locations, and show extensive keratinization, which is where the cytoplasm of the cells is filled with keratin, the same tough material in hair and nails.

Squamous cell carcinomas typically arise in response to chronic irritation like from recurrent urinary tract infections, and long-standing kidney stones.

Another cause, common in some parts of the world, is an infection with Schistosoma haematobium - a type of flatworm. In this infection, the infective larvae linger in the water and then burrow into human skin when given the opportunity, and travel to the liver to mature into adult flukes. From there young flukes migrate to the urinary bladder veins to sexually reproduce and lay eggs in the bladder wall. These eggs can get urinated out, but they also cause chronic inflammation in the bladder wall which is how they lead to squamous cell carcinomas.


Non-urothelial bladder cancers are a small subset of bladder cancers that confusingly, often arise from the urothelium. They include cancers like squamous cell carcinomas completely made of squamous cells, and adenocarcinomas entirely consisting of glandular cells. They are believed to arise from chronic irritation of the bladder, especially from an infection by a flatworm called Schistosoma haematobium. People with non-urothelial bladder cancer may present with hematuria, dysuria, urinary urgency and frequency, and weight loss.


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  3. "Pathophysiology of Disease: An Introduction to Clinical Medicine 8E" McGraw-Hill Education / Medical (2018)
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  6. "Bladder cancer, a review of the environmental risk factors" Environmental Health (2012)
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