Urothelial carcinoma in situ (CIS)

by Jason Wasserman MD PhD FRCPC
August 9, 2022


What is urothelial carcinoma in situ (CIS)?

Urothelial carcinoma in situ (CIS) is a type of non-invasive cancer. It can occur anywhere along the urinary tract which includes the bladder, ureters, urethra, and kidneys. Urothelial CIS arises from specialized urothelial cells that cover the inside surface of these organs and create a barrier called the urothelium. If left untreated, urothelial CIS can change over time into a type of invasive cancer called urothelial carcinoma.

Where is urothelial carcinoma in situ normally found?

Urothelial CIS can start anywhere along the urinary tract which includes the bladder, ureters, kidneys, and urethra. The most common location is the bladder.

What are the symptoms of urothelial carcinoma in situ?

Symptoms associated with urothelial CIS include blood in the urine, pain when urinating, and the need to urinate more frequently or with greater urgency. For some patients, urothelial CIS does not produce any symptoms and the disease is found incidentally (by accident) when tests are performed for another reason.

What causes urothelial carcinoma in situ?

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

Can urothelial carcinoma in situ spread to other parts of the body?

When urothelial CIS occurs on its own, the tumour cells will not spread to other parts of the body. However, urothelial CIS is often found with an invasive type of cancer called urothelial carcinoma which can spread to other parts of the body.

How is the diagnosis of urothelial carcinoma made?

The diagnosis of urothelial CIS is usually made after a small piece of tissue is removed from a part of the urinary tract in a procedure called a biopsy or transurethral resection (TURBT). The tissue is then sent to a pathologist for examination under a microscope. This diagnosis cannot be made from cells collected in a urine sample.

Why is urothelial carcinoma in situ called non-invasive?

Urothelial CIS starts in a thin layer of tissue on the inside of the urinary tract called the urothelium. Invasion is a term pathologists use to describe the movement of tumour cells into surrounding normal tissues. Urothelial CIS is called non-invasive because all of the tumour cells are found within the urothelium. Non-invasive tumour cells are unable to spread to other parts of the body.

What stage is urothelial carcinoma in situ?

When urothelial CIS occurs on its own, it is given the pathologic tumour stage Tis which stands for “in situ” or “non-invasive” disease. When urothelial CIS is found along with an invasive cancer such as urothelial carcinoma, the final tumour stage depends on how far the tumour cells in the urothelial carcinoma have spread into the tissues below the urothelium.

What does urothelial carcinoma in situ look like under the microscope?

When examined under the microscope, abnormal urothelial cells are seen in a thin layer of tissue called the urothelium. The tumour cells are usually larger than normal urothelial cells and the nuclei are hyperchromatic (darker). Pathologists often use the terms atypia or atypical to describe these abnormal tumour cells. 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.

urothelial carcinoma in situ
Urothelial carcinoma in situ. This picture shows abnormal urothelial cells covering the inside surface of the bladder.
What is a margin?

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. Most pathology reports for urothelial CIS do not include information about margins.

Margin

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