Bladder -

Papillary urothelial carcinoma

This article was last reviewed and updated on August 31, 2019

by Jason Wasserman, MD PhD FRCPC

Quick facts:

  • Papillary urothelial carcinoma is a type of bladder cancer.

  • It develops from the cells that line the inside of the bladder.

  • Papillary urothelial carcinoma can also start in the ureters or the urethra.

The bladder and ureters

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 papillary urothelial carcinoma?

Papillary urothelial carcinoma is a type of bladder cancer. Papillary urothelial carcinoma develops from the urothelial cells in the epithelium. The tumour usually starts in the bladder but it can also start in the ureters or urethra.

 

How do pathologists make this diagnosis?

When examined under a microscope, papillary urothelial carcinoma looks like finger-like projections of tissue covered in cancer cells. Pathologists call these projections papilla.

Most papillary urothelial carcinomas are non-invasive which means the cancer cells are only seen in the epithelium. A tumour is called invasive if the cancer cells have traveled out of the epithelium and have entered the lamina propria below.

 

Whether or not a tumour is invasive can only be determined after tissue from the tumour is examined by a pathologist under the microscope. 

The diagnosis of papillary urothelial carcinoma is usually made by looking at a urine sample under the microscope or on a biopsy taken from the bladder. After the diagnosis of urothelial carcinoma is made, the tumour is removed in a resection.

Histologic grade​
Grade is a word pathologists use to describe the difference between the cancer cells and the normal urothelial cells that line the inside of bladder.

 

Papillary urothelial carcinoma is divided into two grades:

 

  • Low-grade - The cancer cells in a low-grade tumour are abnormal but can still look like urothelial cells.

  • High-grade - The cancer cells in a high grade tumour are very abnormal looking and are often hard to recognize as urothelial cells.

Why is this important? Grade is important because compared to low grade tumours, high grade tumours are associated with worse prognosis.​

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.

Presence of 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.

Extent of invasion
All papillary urothelial carcinomas start in the epithelium on the inner surface of the bladder. A tumour called non-invasive papillary urothelial carcinoma means that after careful examination under the microscope, cancer cells were still only seen in the epithelium.

 

In contrast, a tumour called invasive papillary urothelial carcinoma means that the cancer cells have traveled beyond the epithelium into at least the lamina propria below. The movement of cancer cells from the epithelium into the lamina propria is called invasion.

When examining an invasive papillary urothelial carcinoma, extent of invasion is used to describe how far the cancer cells have traveled from the epithelium into the wall of the bladder.

After examining the tumour under a microscope, your pathologist will describe the extent of invasion as one of the following:

 

  • Carcinoma in situ - The cancer cells are only seen in the epithelium. They have not entered the lamina propria below the inner surface of the bladder. 

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

  • Muscularis propria - The cancer cells that have entered the thick muscular 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 papillary 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 the normal tissue that surrounds a tumour and is removed with the tumour at the time of surgery. In papillary urothelial carcinoma, a margin is considered positive when there is no distance between the cancer cells and the cut edge of the tissue. A negative margins means that no cancer cells were seen at the cut edge of the tissue.

Margins will only be described in your report after the entire tumour has been removed.


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.

Lymph nodes on the same side as the tumour are called ipsilateral while those on the opposite side of the tumour are called contralateral.

Why is this important? The number of lymph nodes found to contain cancer cells is used to determine the nodal stage (see Pathologic stage below). Finding cancer cells in a lymph node is associated with worse prognosis and may require additional treatment.

Pathologic stage

​The pathologic stage for papillary 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) for papilary urothelial carcinoma:

All non-invasive papillary urothelial carcinomas are given a special classification called Ta in order to indicate their non-invasive status. In contrast, all invasive papillary urothelial carcinomas is given a tumour stage from T1 to T4 based on the extent of tumour invasion (see Extent of invasion above).

 

  • Ta: Non-invasive tumours.

  • T1: The tumour cells have entered the lamina propria just below the epithelium.

  • T2: The tumour cells have entered the thick muscular wall of the bladder.

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

  • T4: The tumour cells have invaded organs around the bladder such as the prostate, uterus, or pelvic wall.


Nodal stage (pN) for papillary urothelial carcinoma:

Papillary 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) for papillary urothelial carcinoma: 

Papillary urothelial carcinoma is given a metastatic stage of M0 or M1 based on the presence of cancer cells at a distant site in the body (for example the lungs). The metastatic stage can only be determined 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 MX.

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