Papillary urothelial carcinoma

by Jason Wasserman MD PhD FRCPC and Zuzanna Gorski MD
October 2, 2023

What is papillary urothelial carcinoma?

Papillary 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. The tumour is made up of urothelial cells that normally cover the inside surface of the urinary tract.

Where does papillary urothelial carcinoma start?

Papillary urothelial carcinoma starts from specialized urothelial cells that cover the inside surface of the urinary tract and create a barrier called the urothelium.

What are the symptoms of papillary urothelial carcinoma?

Symptoms of papillary urothelial carcinoma include bloody urine (hematuria), pain when urinating (dysuria), and the need to urinate more frequently.

What causes papillary urothelial carcinoma?

Studies have shown that a wide variety of toxins, medications, and infections are associated with an increased risk of developing papillary urothelial carcinoma. Toxins that can cause this type of cancer include tobacco smoke, opium, benzidine-based dyes, aromatic amines, arsenic, and aristolochic acid produced by Aristolochia plants (which are commonly used in herbal medications). Chronic (long-term) inflammation in the bladder caused by infections such as the Schistosoma haematobium, prolonged indwelling catheter, and some medical treatments including radiation to the pelvis and chemotherapy with chlornaphazine or cyclophosphamide are associated with an increased risk of developing this type of cancer in the bladder.

How is this diagnosis made?

The diagnosis 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. After the diagnosis is made, the entire tumour is usually removed in a procedure called transurethral resection (TURBT). 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 it mean if papillary urothelial carcinoma is described as low grade or high grade?

Pathologists divide papillary urothelial carcinoma into two grades – low and high – based on how the tumour cells look when examined under the microscope. A low grade tumour is made up of cells that look more like normal urothelial cells. In contrast, a high grade tumour is 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.​

What does it mean if the tumour is described as non-invasive?

Papillary urothelial carcinoma is described as non-invasive when the tumour cells are only seen in the urothelium. Most tumours are non-invasive. Non-invasive tumours are unable to spread to other parts of the body and are cured by surgery alone.

What does it mean if the tumour is described as invasive?

Papillary urothelial carcinoma is described as invasive if the tumour cells have spread into the layers of tissue below the urothelium. These layers include the lamina propria, muscularis propria, and perivesical soft tissue. Unlike non-invasive tumours, invasive tumours can spread to other parts of the body.

What does the depth of invasion mean and why is it important?

The distance that the tumour cells have spread 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).

How is papillary urothelial carcinoma staged?

​The pathologic stage is based on the TNM staging system, an internationally recognized system 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 a more advanced disease and a worse prognosis.

Tumour stage (pT)

All non-invasive tumours are given a special classification called Ta to indicate their non-invasive status. In contrast, all invasive tumours are given a tumour stage from T1 to T4 based on the depth of invasion.

• Ta – Non-invasive tumours.
• 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)

Papillary urothelial carcinoma is given a nodal stage between 0 and 3 based on the number of lymph nodes that contain tumour 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.