High grade papillary urothelial carcinoma

by Jason Wasserman MD PhD FRCPC and Zuzanna Gorski MD
January 3, 2024


High grade 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 kidneys, bladder, ureters, and urethra. Most tumours are found in the bladder. Pathologists divide this type of cancer into non-invasive and invasive based on the presence of tumour cells in the tissue below the urothelium, a thin layer of tissue on the inside surface of the urinary tract. This distinction is important because non-invasive tumours are typically cured through surgery alone while patients with invasive tumours may require additional treatment after surgery.

This article will help you understand your diagnosis and your pathology report for high grade papillary urothelial carcinoma.

The urinary tract

The urinary tract is a system designed to help remove waste and excess water from the body through the production of urine. The urinary tract includes the kidneys, ureters, bladder, and urethra. Urine made in the kidneys flows into the bladder by way of the ureters. The bladder stores the urine until it is released from the body by way of the urethra. The inside surface of the entire urinary tract is lined by specialized urothelial cells that form a barrier called the urothelium.

Urothelium

What are the symptoms of high grade papillary urothelial carcinoma?

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

What causes high grade 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.

High grade papillary urothelial carcinoma

High grade papillary urothelial carcinoma starts from the urothelial cells normally found in the urothelium, a thin layer of tissue that covers the inside surface of the urinary tract. Although this tumour is most commonly found in the bladder, it can arise anywhere along the length of the urinary tract. The tumour is described as high grade because the tumour cells look very abnormal when examined under the microscope. As the tumour grows it forms long finger-like projections of tissue that stick out from the inside surface of the tissue. Pathologists use the term papillary to describe this pattern of growth.

Noninvasive and invasive tumours

Most high grade papillary urothelial carcinomas are non-invasive which means that the tumour is confined to the urothelium on the inside surface of the urinary tract. Non-invasive tumours are unable to spread to other parts of the body and are cured by surgery alone.

Noninvasive papillary urothelial carcinoma

However, some tumours evolve into invasive tumours which means that the tumour has spread into the tissue below the urothelium (for example, the lamina propria or muscularis propria). Unlike non-invasive tumours, invasive tumours can spread to lymph nodes and other parts of the body.

When examining an invasive high grade papillary urothelial carcinoma, your pathologist will try to determine how far the tumour cells have spread into the layers of tissue below the urothelium. This information is very important because tumours that invade deeper into the surrounding tissue are more likely to spread to other parts of the body. This information is also used to determine the pathologic tumour stage (pT).

Invasive papillary urothelial carcinoma

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.

Why is it important to sample the muscularis propria?

The muscularis propria is a thick layer of muscle inside the wall of the bladder. When doctors remove a tumour in the bladder, they try to remove some of the underlying muscularis propria at the same time. Sampling of the muscularis propria is important because pathologists cannot rule out muscle-invasive disease until the muscle is examined under the microscope. For this reason, after a TURBT is performed, most pathology reports will say whether muscularis propria was seen or not in the tissue provided.

Pathologic stage

​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.

About this article

This article was written by doctors to help you read and understand your pathology report. Contact us if you have any questions about this article or your pathology report. Read this article for a more general introduction to the parts of a typical pathology report.

Other helpful resources

Atlas of Pathology
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