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. 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. Urothelial CIS arises from specialized urothelial cells that cover the inside surface of these organs and create a barrier called the urothelium.

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 are 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 is called “non-invasive” because the tumour cells are found entirely within a thin layer of tissue called 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 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.