Urothelial cells line the urinary tract, forming a protective barrier. When these cells appear “atypical,” they show changes from their normal appearance. This finding often raises concerns about cancer, but atypical cells are not definitively cancerous. Instead, they signal a need for further investigation into the underlying cause of these cellular changes.
What Are Atypical Urothelial Cells?
Urothelial cells, also known as transitional cells, create the inner lining of the urinary system, including the kidneys, ureters, bladder, and urethra. This specialized lining, called the urothelium, forms a barrier that prevents urine from entering surrounding tissues. Urothelial cells are unique because they can stretch and contract, allowing the bladder to accommodate varying volumes of urine.
When a pathologist identifies “atypical” urothelial cells, it indicates these cells display unusual features under a microscope. These changes might include variations in cell shape, size, or nuclear appearance, such as an enlarged nucleus with a high nuclear-to-cytoplasmic ratio. However, these abnormalities are not severe enough to be definitively classified as cancerous. The term “atypical” is a descriptive classification that suggests cellular changes exist, but it does not confirm a cancer diagnosis.
Why Atypical Cells Appear
Atypical urothelial cells can arise from various causes, ranging from benign, reactive processes to more serious pre-cancerous conditions. Inflammation is a common reason for cells to appear atypical, often stemming from urinary tract infections, kidney stones, or irritation caused by medical instruments like catheters. Even radiation therapy can induce atypical changes in healthy cells. In these scenarios, the cellular changes are often temporary and can revert to normal once the underlying irritation or inflammation resolves.
Atypical cells can also be a reaction to medical conditions or treatments. For instance, after certain bladder treatments like Bacillus Calmette-Guerin (BCG) therapy, atypical cells are expected due to the inflammatory response induced in the bladder lining. In such cases, the atypical appearance reflects the body’s reaction to therapy rather than a progression towards cancer. While these reactive changes can mimic cancer, they are distinct from true malignant transformation.
How Atypical Cells Are Diagnosed
The initial detection of atypical urothelial cells occurs through a urine cytology test, which examines a urine sample for abnormal cells. This non-invasive test screens for infection, inflammatory disease, and potentially cancerous or pre-cancerous conditions of the urinary tract. While urine cytology is useful for detecting high-grade urothelial carcinoma, its ability to definitively identify low-grade cancer cells is limited.
If atypical cells are found, further diagnostic procedures are usually recommended to determine their significance. These may include repeat urine cytology tests to monitor the persistence or progression of the atypical cells. Imaging studies, such as CT scans or ultrasounds, might be performed to visualize the urinary tract. A cystoscopy, where a doctor uses a thin scope to look inside the bladder and urethra, is often necessary to directly examine the bladder lining and collect tissue samples through a biopsy for a more definitive diagnosis. This comprehensive approach helps clarify whether the atypical cells are benign or indicate a more serious condition.
The Spectrum of Urothelial Cell Changes
The spectrum of urothelial cell changes ranges from reactive atypia to various stages of pre-cancer and cancer. Beyond reactive atypia, which is typically benign, the classification progresses to more concerning categories. Urothelial dysplasia, also known as low-grade dysplasia, represents a pre-malignant lesion where cells show mild nuclear changes and some architectural disorganization. This condition signifies cellular instability and can progress to cancer in some cases, requiring active clinical follow-up.
A more advanced pre-cancerous condition is carcinoma in situ (CIS), also known as high-grade dysplasia. CIS involves severe cellular abnormalities, including enlarged and irregular nuclei, that affect the full thickness of the urothelium but have not yet invaded beyond the lining. The most serious finding is invasive urothelial carcinoma, where malignant cells have broken through the basement membrane and invaded deeper tissues. This is the most common type of bladder cancer. Approximately 10-20% of patients with atypical cells may eventually be diagnosed with urothelial carcinoma, with a higher risk in individuals with hematuria, a smoking history, or a prior diagnosis of bladder cancer.