The finding of “atypical urothelial cells” (AUC) in a urine test is a common source of patient concern, but it is not a diagnosis of cancer. Urothelial cells line the entire urinary tract. Pathologists use the term “atypical” to describe cells that show microscopic changes or abnormalities that cannot be classified as definitively cancerous or definitively benign. This classification of uncertainty requires further medical investigation. While often benign, AUC can sometimes indicate an underlying pre-cancerous or cancerous condition.
Understanding Urothelial Cells and Cytology
Urothelial cells are a unique type of epithelial cell that form the lining (urothelium) of the urinary tract. This specialized, multi-layered lining extends from the renal pelvis in the kidneys, through the ureters, into the bladder, and down to the urethra. The primary function of the urothelium is to act as an impermeable barrier, protecting underlying tissues from the toxic components in urine.
A distinctive feature of these cells is their ability to stretch and contract, allowing the bladder to fill and empty while maintaining a protective seal. Cells naturally shed from this lining into the urine, which is the basis for urine cytology. In this non-invasive procedure, a pathologist examines a urine sample under a microscope to look for abnormal or malignant cells.
Cytology is particularly effective at detecting high-grade lesions because malignant cells from these tumors shed into the urine more readily. The identification of abnormal cells that do not meet the criteria for malignancy leads to the classification of “atypical urothelial cells.” This classification signifies that the cells exhibit changes in size, shape, or nuclear features that fall into a gray area between normal and cancerous.
Decoding “Atypical”: Non-Cancerous Causes of Cell Change
An AUC finding is a non-specific classification, meaning it can be caused by numerous non-malignant conditions. Many benign processes cause urothelial cells to react and change their appearance, mimicking the abnormalities seen in early malignancy. This reactive change is a common biological response to stress or irritation within the urinary tract.
Inflammation, such as a urinary tract infection (UTI) or cystitis, is a frequent cause of atypical cellular changes. Urinary tract stones (calculi) can also mechanically irritate the urothelium, leading to reactive changes in the exfoliated cells. Even recent medical procedures, like catheter insertion or other instrumentation, can cause temporary cellular changes classified as atypical.
Certain treatments, including radiation therapy or intravesical chemotherapy, are also known to cause significant cellular atypia. For example, the inflammatory response triggered by Bacillus Calmette-Guérin (BCG) treatment for bladder cancer often causes subsequent cytology results to show atypical cells. Therefore, the pathologist must consider the patient’s full clinical history to differentiate between true pre-cancerous change and benign reactive atypia.
The Spectrum of Risk and Potential Diagnoses
While many AUC findings are benign, the category is clinically significant as a potential marker for urothelial carcinoma. Studies indicate that 10% to 20% of patients with an initial AUC result may eventually be diagnosed with urothelial carcinoma. The risk is higher in those with factors like smoking history or blood in their urine, necessitating a comprehensive risk assessment by a urologist.
The risk associated with AUC depends on the specific type of cellular change present. A less aggressive form is the low-grade category, which includes low-grade papillary urothelial carcinoma (LGPUNC). These tumors are typically slow-growing, less likely to invade the bladder muscle, and have a lower chance of spreading. However, cells shed from low-grade tumors are often subtly abnormal and difficult to detect reliably with urine cytology, leading to low sensitivity for this tumor type.
Of greater concern is the possibility that AUC is associated with high-grade disease, such as high-grade urothelial carcinoma (HGUC) or carcinoma in situ (CIS). HGUC cells look very abnormal under the microscope, grow more quickly, and are more likely to recur or spread. Cytology is valuable in detecting high-grade lesions because the malignant cells have pronounced features, such as a high nuclear-to-cytoplasmic ratio and irregular nuclear membranes, and are more prone to shedding.
The Paris System for Reporting Urinary Cytology standardizes the interpretation of these findings, focusing attention on the features of high-grade disease. An AUC classification is a warning sign, indicating the cytologist could not definitively classify the cells as benign or malignant. This requires the urologist to intervene with more specific diagnostic tools.
Required Follow-Up and Diagnostic Procedures
Following an AUC report, the standard medical approach is a focused investigation to rule out malignancy. The management plan is determined by the patient’s individual risk factors, but it generally involves further testing to visualize the entire urinary tract.
The first step often involves repeating the urine cytology test in three to six months to see if the atypical finding is persistent or resolves. The urologist will typically perform a cystoscopy, which involves inserting a thin, lighted tube with a camera into the bladder through the urethra. This allows for a direct, visual examination of the bladder lining to identify any suspicious lesions or growths.
To ensure the entire urinary tract is evaluated, imaging of the upper tract is standard procedure. This commonly involves a CT urogram, which uses contrast dye and CT scans to visualize the kidneys and ureters, where urothelial cancer can occur. If suspicious areas are noted during the cystoscopy, a biopsy will be performed to obtain tissue for a definitive diagnosis. Consulting with a specialist is the most important step to manage the risk and establish a definitive diagnosis.