Transitional cell carcinoma

The most common form of cancer in the lower urinary tract—or the bladder and the urethra— is transitional cell carcinoma (or TCC), and to be more specific, urothelial cell carcinoma (or UCC).

While this cancer can affect tissues in the upper urinary tract, such as the renal pelvis and the ureter, it most commonly arises in the urothelium of the bladder.

The urothelium (or uroepithelium) is a specific type of transitional cell epithelium that lines the inner surface of much of the urinary tract. This tissue is composed of 3–7 cell layers, and it forms a tight barrier which holds urine without allowing toxins to move across the epithelium and back into the body.

That barrier function is largely accomplished by large umbrella cells that line the inner or luminal surface of the urothelium, and are held together by high resistance tight junctions, and are lined with a unique protein/lipid complex, called a plaque, along their apical membrane.

Now when you think about the bladder, it’s going to cyclically change shape during the course of its normal function.

For example, after you chug a tall mango lassi, your bladder will become completely filled up only to be emptied again when you rush to the restroom. Therefore, the urothelium has to be able to maintain its impermeable properties during these normal changes in bladder shape. Most of this is allowed for by the unfolding of the mucosal surface when the bladder fills up.

When the bladder is empty, this surface is highly wrinkled with rugae which then smooths out as the bladder becomes distended. In addition to this, these umbrella cells of the urothelium, have the ability to stretch with an expanding bladder. In fact, the term “transition” of transitional epithelium refers to this ability to go through transitions of shape.

Cancers that affect the urothelium usually arise through two distinct mechanisms. One way for a urothelial cell carcinoma to arise is through a mutation in the tumor suppressor protein p53.

Mutations in p53 can allow urothelial cells to start growing horizontally like a flat pancake, some of which begin to invade deeper bladder tissues.

The other, less aggressive way for a urothelial cell carcinoma to arise is independent of p53 mutations, and occurs when finger like extensions called papillary tumors grow outward from the urothelium. Although, these can can occasionally invade deeper bladder tissues as well.

Regardless of the cause of the urothelial cell carcinoma invasion, a telltale sign of the presence of the cancer is the presence of red blood cells in the urine, a typically painless condition known as hematuria.

To make a definitive diagnosis, it's possible to look at the inside of the bladder with as cystoscope, which is a thin flexible tube fitted with a light, and a camera that is inserted up the urethra and into the bladder—a procedure called cystoscopy. This tool can also be used to take biopsies which are used for a subsequent histological analysis.

Urothelial cell cancers most commonly occur in older patients, and have been linked to various carcinogens.