Urothelial carcinoma

by Jason Wasserman MD PhD FRCPC
March 3, 2022

What is urothelial carcinoma?

Urothelial carcinoma is a type of cancer that starts in a part of the body called the urinary tract. The urinary tract includes the bladder, ureters, urethra, and kidneys. Most tumours are found in the bladder. Urothelial carcinoma arises from specialized urothelial cells that cover the inside surface of these organs and create a barrier called the urothelium.

How is the diagnosis of urothelial carcinoma made?

The diagnosis of urothelial carcinoma is usually made by looking at a urine sample under a microscope. The diagnosis can also be made after a small sample of tissue is removed from the urinary tract during a procedure called a biopsy. For larger tumours that involve the bladder or kidney, part or all of the organ may need to be removed in a procedure called a resection.

What does urothelial carcinoma look like under the microscope?

When examined under the microscope, the tumour cells in urothelial carcinoma look very abnormal compared to healthy urothelial cells. Pathologists use the terms atypia or atypical to describe these cells. For example, the tumour cells are usually larger than normal urothelial cells and the nuclei are hyperchromatic (darker).  Mitotic figures (tumour cells dividing to create new tumour cells) are also usually seen and some may be described as atypical mitotic figures because they are dividing abnormally.

Tumour grade

Pathologists divide urothelial carcinoma into two grades – low and high based on how the tumour cells look when examined under the microscope. Low-grade tumours are made up of cells that look more like normal urothelial cells while high-grade tumours are made up of more abnormal looking cells that tend to be larger, darker, and less organized than normal urothelial cells.​ The grade is important because high-grade tumours are more likely to re-grow after treatment and spread to other parts of the body.​

Variants of urothelial carcinoma

Most urothelial carcinomas are made up of tumour cells that look similar to the urothelial cells normally found in the urinary tract. However, some tumours are made up of cells that look very different. Pathologists use the term ‘variant’ or ‘variant histology’ to describe these tumours.

Common variants of urothelial carcinoma include nested, micropapillary, microcystic, plasmacytoid, lymphoepithelioma-like, clear cell, poorly differentiated, and sarcomatoid. Urothelial carcinoma with squamous differentiation is a specific type of variant where the tumour cells start to look like specialized squamous cells normally found in other parts of the body such as the skin.

Some variants such as nested, microcystic, sarcomatoid, micropapillary, and poorly differentiated are aggressive tumours that are more likely to spread into surrounding tissues and other parts of the body.

Depth of invasion

All urothelial carcinomas start in a thin layer of tissue called the urothelium that covers the inside surface of the urinary tract. As the tumour grows, the tumour cells spread into the layers of tissue below the urothelium. These layers include the lamina propria, muscularis propria, and perivesical soft tissue.

The distance that the tumour cells have travelled is called the depth of invasion and it can only be determined after the tumour is examined under the microscope. The depth of invasion is very important because tumours that invade deeper into the surrounding tissue are more likely to spread to other parts of the body. The depth of invasion is also used to determine the pathologic tumour stage (pT).

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 specialized vessels called lymphatics. The term lymphovascular invasion is used to describe tumour cells that are found inside a blood or lymphatic vessel. Lymphovascular invasion is important because these cells are able to metastasize (spread) to other parts of the body such as lymph nodes or the lungs.

lymphovascular invasion

Lymph nodes

Lymph nodes are small immune organs located throughout the body. Tumour 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 tumour cells from the tumour to a lymph node is called metastasis.

Your pathologist will carefully examine all lymph nodes for tumour cells. Lymph nodes that contain tumour 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 tumour 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.

The number of lymph nodes found to contain tumour cells is used to determine the pathologic nodal stage (pN). Finding tumour cells in a lymph node is associated with a worse prognosis and may require additional treatment.

Lymph node


A margin is the normal tissue that surrounds a tumour and is removed with the tumour at the time of surgery. A negative margin means that no tumour cells were seen at the cut edge of the tissue. A margin is called positive when there is no distance between the tumour and the cut edge of the tissue. A positive margin is associated with a higher risk that the tumour will grow back (recur) in the same location after treatment.


Pathologic stage for urothelial carcinoma

​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 (pT), lymph nodes (pN), and distant metastatic disease (pM)  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 a worse prognosis.

Tumour stage (pT) for urothelial carcinoma

Urothelial carcinomas are given a tumour stage from 1 to 4 based on the depth of invasion.

  • T1 – The tumour cells have entered the lamina propria just below the urothelium.
  • T2 – The tumour cells have spread into the muscularis propria.
  • T3 – The tumour cells are in the perivesical soft tissue.
  • T4 – The tumour cells have invaded surrounding organs such as the prostate, uterus, or pelvic wall.
Nodal stage (pN) for urothelial carcinoma

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 tumour cells are seen in any of the lymph nodes examined.
  • N1 – Tumour cells are found in one lymph node in the pelvis.
  • N2 – Tumour cells are found in more than one lymph node in the pelvis.
  • N3 – Tumour cells are found in the common iliac lymph nodes which are located outside of the pelvis.
  • NX – No lymph nodes were sent for pathologic examination.
Metastatic stage (pM) for urothelial carcinoma

Urothelial carcinoma is given a metastatic stage of 0 or 1 based on the presence of tumour 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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