When a laboratory report indicates the presence of cancer cells in a urine sample, it means that cells with abnormal features have been shed from the lining of the urinary tract. This finding is typically the result of a specialized test called urine cytology, often performed during a workup for symptoms like blood in the urine (hematuria). The presence of these malignant cells indicates potential pathology within the urinary system, requiring detailed investigation. While the test is not a final diagnosis, a positive result signals a high suspicion for a cancerous or pre-cancerous condition somewhere along the urinary tract.
Cancers That Shed Cells into Urine
The primary source of cancer cells found in urine originates from the urothelium, the specialized tissue lining the entire urinary tract from the kidneys down to the bladder and urethra. Cancer arising from these cells is called urothelial carcinoma, previously known as transitional cell carcinoma. The location of these tumors, in direct contact with the urine, facilitates the shedding of malignant cells into the fluid stream.
Bladder cancer represents the vast majority of urothelial carcinomas, accounting for approximately 90% of all cases. As a tumor grows on the inner surface of the bladder, its cells naturally detach and mix with the urine before it is voided. This makes the bladder the most common anatomical source for malignant cells detected in a urine sample.
Urothelial carcinoma can also occur in the upper urinary tract, specifically in the renal pelvis and the ureters. Though tumors in these upper tract locations are much rarer than bladder cancer, they are also composed of urothelial cells and will shed into the urine. A positive cytology result can therefore indicate a tumor anywhere along this continuous lining.
In rare instances, non-urothelial tumors may also contribute to the finding. Kidney cancers, such as renal cell carcinoma, are less likely to shed cells into the urine stream unless the tumor is advanced or has invaded the collecting system of the kidney. Therefore, the detection of cancer cells points most strongly toward urothelial carcinoma.
Methods for Detecting Cancer Cells
The primary laboratory technique for identifying these exfoliated cells is urine cytology. This method involves preparing the collected urine sample onto glass slides, which are then stained and examined under a microscope by a specialized physician called a cytopathologist. The pathologist looks for specific cellular characteristics that indicate malignancy, such as an enlarged nucleus, irregular nuclear membranes, and a darker, clumped appearance of the genetic material (hyperchromasia).
Traditional analysis is often complemented by newer, more sensitive molecular tests. These advanced methods analyze the urine sample for genetic changes or specific biomarkers associated with cancer, rather than relying solely on the cell’s appearance. For example, some assays use Fluorescence In Situ Hybridization (FISH) to detect abnormalities in the number of chromosomes within the urothelial cells.
Molecular tests may also search for specific cancer-related mutations, such as those in the TERT promoter gene, which is frequently altered in urothelial carcinoma. These molecular approaches offer a standardized, objective measure to support or clarify traditional cytology findings. While cytology remains the established, cost-effective initial screening tool, molecular markers are increasingly used to improve the detection of tumors.
Understanding the Test Results
A urine cytology report typically uses specific terminology to classify the findings into a spectrum of risk. A “negative” result means the pathologist found no evidence of malignant cells, suggesting a low likelihood of high-grade urothelial carcinoma. Conversely, a “positive” result indicates that cells with definitive malignant features were identified, making the presence of cancer highly probable.
Between these clear-cut findings is the category of “atypical” or “suspicious” cells. An atypical result means the cells show some abnormal features, such as slight nuclear enlargement, but they do not meet all the criteria for a definitive diagnosis of cancer. This ambiguous finding can be caused by inflammation, infection, kidney stones, or recent instrumentation, but it still carries a low to moderate risk of cancer.
A significant limitation of urine cytology is its variable accuracy based on the tumor’s grade. The test is highly specific for high-grade urothelial carcinoma, meaning a positive result is reliable. However, its sensitivity for low-grade tumors is poor, often resulting in a false-negative. Low-grade tumors shed fewer cells that look less abnormal, making them difficult to distinguish from benign changes. Therefore, a negative result does not completely rule out the presence of a low-grade tumor.
Next Steps After Detection
The detection of cancer cells or atypical cells mandates a thorough follow-up to confirm the exact location and nature of the pathology. The most common next step is a procedure called cystoscopy, where a physician inserts a thin, lighted tube into the bladder through the urethra. This allows for a direct visual inspection of the entire bladder lining to identify any visible tumors or suspicious areas.
To evaluate the entire urinary system, the physician will also order specialized imaging, such as a computed tomography (CT) urogram. This scan uses intravenous contrast dye to visualize the kidneys, renal pelvis, and ureters. This is important to ensure there is no tumor originating in the upper urinary tract, as cystoscopy only visualizes the bladder.
If a suspicious lesion is found during cystoscopy or through imaging, a tissue biopsy is required for a definitive diagnosis. Biopsies provide the tissue sample necessary for a final histopathological examination. Only through this analysis can the doctor confirm the presence of cancer, determine its type, and establish its severity or grade, which dictates the appropriate treatment plan.

