Non-urothelial bladder cancers

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.

Primary adenocarcinomas of the bladder are more rare, but unlike squamous cell carcinomas, they frequently metastasize. These are usually solitary, and derive from glandular tissue, so they can often produce a lot of mucin.

Adenocarcinomas are the main form of bladder tumors in patients with bladder exstrophy, which is where the bladder protrudes through a birth defect in the abdominal wall and partially or completely sits outside of the body.

Adenocarcinomas can also develop in response to Schistosoma haematobium infections.

Finally, it’s worth noting that adenocarcinomas of the urachus are quite similar to bladder adenocarcinomas. The urachus is the fibrous tissue sitting at the dome of the bladder which serves as the remnant of the allantois, the canal that allows urine to flow from the fetal bladder into the amniotic sac.