Bladder, ureters, and urethra -

Urothelial carcinoma

This article was last reviewed and updated on June 27, 2019
by Jason Wasserman, MD FRCPC

Quick facts:

  • Urothelial carcinoma is a type cancer.

  • It starts from the cells that line the inside of the bladder, ureters, or urethra. 

  • The most common location for urothelial carcinoma is the bladder.

  • Movement of cancer cells into the muscle of the bladder wall is an important feature that will impact the treatment you receive.

The normal bladder

The bladder is a hollow organ located in the pelvis. The purpose of the bladder is to store urine and then to release it out of the body through a tube called the urethra. Urine is made in the kidneys and travels to the bladder by two long tubes called ureters.

The inside of the bladder is lined by cells called urothelial cells. These cells form a barrier on the inner surface of the bladder called an epithelium. The tissue directly below the epithelium is called the lamina propria. The inside of the ureters and urethra are also lined by urothelial cells.

 

What is urothelial carcinoma?
Urothelial carcinoma is a type of cancer. This type of cancer can start in the bladder, ureters, or urethra. It develops from the urothelial cells in the epithelium.

 

When the cancer cells are only seen in the epithelium, the disease is called urothelial carcinoma in situ. When the cancer cells break out of the epithelium and enter the lamina propria, the diagnosis changes to urothelial carcinoma. The movement of cancer cells from the epithelium into the lamina propria is called invasion.

The diagnosis of urothelial carcinoma is usually made after a pathologist looks at a urine sample or biopsy taken from the bladder through a microscope. After the diagnosis of urothelial carcinoma is made, the tumour is removed in a resection.

Variants

There are different kinds of urothelial carcinoma and each is called a variant. Your pathologist will determine the variant by examining the tissue under the microscope and looking at the size and shape of the cancer cells and the way they stick together as they grow. 

The most common variant is called conventional. Because it is so common, most reports will leave out the word conventional and simply say "invasive urothelial carcinoma". However tumours that are made up of a less common variant are given a special name. If your pathologist sees one of these less common variants in your tissue sample, it will be described in your pathology report.

 

Less common histologic variants of urothelial carcinoma include:

 

Why is this important? The nested, microcystic, sarcomatoid, micropapillary, and poorly differentiated variants present at a higher stage and are associated with more aggressive tumour behavior and worse prognosis.

Histologic grade​
Pathologists use the word grade to describe how different the cancer cells in urothelial carcinoma look compared the urothelial cells normally found in the bladder, ureters, and urethra.

 

Pathologists divide the grade into two categories based on how the cancer cells look when examined under the microscope.

 

  • Low grade - The tumour cells look similar to normal urothelial cells.

  • High grade - The tumour cells look very little like urothelial cells and additional tests such as immunohistochemistry may be needed to confirm that the tumour is a urothelial carcinoma.


Why is this important? Most urothelial carcinomas are high grade.​

Tumour size

This is the size of the tumour measured in centimeters (cm). Tumour size will only be described in your report after the entire tumour has been removed. The tumour is usually measured in three dimensions but only the largest dimension is described in your report. For example, if the tumour measures 4.0 cm by 2.0 cm by 1.5 cm, your report will describe the tumour as being 4.0 cm.

Muscularis propria

There is a thick bundle of muscle in the wall of the bladder called the muscularis propria. When the bladder is full of urine, the muscularis propria squeezes which forces all of the urine out of the bladder and into the urethra.

The muscularis propria is found in the middle of the wall of the bladder below the lamina propria. Cancer cells that travel past the lamina propria can enter the muscularis propria. The movement of cancer cells into the muscularis propria is called invasion.

When examining a tissue sample from your bladder under the microscope, your pathologist will look for muscularis propria. If there is no muscularis propria in the tissue sample, your pathologist will not be able to say if there is invasion of the muscularis propria.

Why is this important? Invasion of the muscularis propria by cancer cells increases the tumour stage (see Pathologic stage below) and is associated with worse prognosis.

Tumour extension

All urothelial carcinomas start in the epithelium on the inner surface of the bladder, ureter, or urethra. Tumour extension describes how far the cancer cells have traveled from the epithelium into the deeper layers of tissue under the epithelium. The movement of cancer cells from the epithelium into the tissue below is called invasion.

The extent of invasion will be described in your report as follows:

 

  • Urothelial carcinoma in situ - The cancer cells are only seen in the epithelium. This is a non-invasive type of cancer.

  • Lamina propria - The cancer cells have broken out of the epithelium and are in the lamina propria just below the inner surface.

  • Muscularis propria - The cancer cells that have entered the thick muscle that sits in the middle of the wall of the bladder.

  • Perivesical tissue - The cancer cells that have gone through the entire wall of bladder and are touching the outer surface of the bladder.


Why is this important? The extent of invasion plays a very important role in the staging of urothelial carcinoma (see Pathologic stage below) and is the most important feature when determining the type of treatment that will be offered.

Lymphovascular invasion

Blood moves around the body through long thin tubes called blood vessels. Another type of fluid called lymph which contains waste and immune cells moves around the body through lymphatic channels.

Cancer cells can use blood vessels and lymphatics to travel away from the tumour to other parts of the body. The movement of cancer cells from the tumour to another part of the body is called metastasis.

 

Before cancer cells can metastasize, they need to enter a blood vessel or lymphatic. This is called lymphovascular invasion.

Why is this important? Lymphovascular invasion increases the risk that cancer cells will be found in a lymph node or a distant part of the body such as the lungs.

Margins
A margin is any tissue that has to be cut by the surgeon in order to remove the tumour from your body. In urothelial carcinoma, a margin is considered positive when there is no distance between the cancer cells and the cut edge of the tissue.


Why is this important? A positive margin is associated with a higher risk that the tumour will recur in the same site after treatment.

Lymph nodes

Lymph nodes are small immune organs located throughout the body. Cancer cells can travel from the tumour to a lymph node through lymphatic channels located in and around the tumour (see Lymphovascular invasion above). The movement of cancer cells from the tumour to a lymph node is called a metastasis


Your pathologist will carefully examine all lymph nodes for cancer cells. Lymph nodes that contain cancer cells are often called positive while those that do not contain any cancer cells are called negative. Most reports include the total number of lymph nodes examined and the number, if any, that contain cancer cells. 


Why is this important? Finding cancer cells in a lymph node is important because it is associated with a higher risk that the cancer cells will be found in other lymph nodes or in a distant organ such as the lungs. 

Pathologic stage

​The pathologic stage for urothelial carcinoma is based on the TNM staging system, an internationally recognized system originally created by the American Joint Committee on Cancer.

 

This system uses information about the primary tumour (T), lymph nodes (N), and distant metastatic disease (M)  to determine the complete pathologic stage (pTNM). Your pathologist will examine the tissue submitted and give each part a number. In general, a higher number means more advanced disease and worse prognosis.

 

Pathologic stage is not reported on a biopsy specimen. It is only reported when the entire tumour has been removed in an excision or resection specimen.

Tumour stage (pT)

Urothelial carcinoma is given a tumour stage from 1 to 4 based on the amount of tumour extension (see Tumour extension above). 

  • Tis: This stage is called urothelial carcinoma in situ. The cancer cells are only seen in the epithelium. There is no invasion.

  • T1: Cancer cells are seen in the lamina propria just below the epithelium.

  • T2: The cancer cells have entered the thick muscle in the middle of the wall of the bladder.

  • T3: The cancer cells have gone through the entire wall of the bladder and are on the outer surface of the bladder.

  • T4: The cancer cells have gone through the entire wall of the bladder and entered adjacent organs such as the prostate, uterus, or pelvic wall.

 

Nodal stage (pN)

Urothelial carcinoma is given a nodal stage between 0 and 3 based on the number of lymph nodes that contain cancer cells and the location of those lymph nodes.

  • ​N0: No cancer cells are seen in any of the lymph nodes examined.

  • N1: Cancer cells are found in one lymph node in the pelvis.

  • N2: Cancer cells are found in more than one lymph node in the pelvis.

  • N3: Cancer cells are found in the common iliac lymph nodes which are located outside of the pelvis.

If no lymph nodes are sent for pathological examination, the nodal stage cannot be determined and the nodal stage is listed as pNX.

Metastatic stage (pM)

Urothelial carcinoma is given a metastatic stage of 0 or 1 based on the presence of cancer cells at a distant site in the body (for example the lungs). The metastatic stage can only be assigned if tissue from a distant site is submitted for pathological examination. Because this tissue is rarely present, the metastatic stage cannot be determined and is listed as pMX.

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