Urine cytology is a laboratory test used to examine cells found in a urine sample under a microscope. Unlike a routine urinalysis, which evaluates substances such as protein, glucose, blood, and other chemical or physical characteristics of urine, urine cytology focuses specifically on the appearance and characteristics of urinary cells.
Healthcare professionals may order urine cytology when they need to investigate abnormal urinary findings, persistent urinary symptoms, blood in the urine, or abnormalities involving the urinary tract. The test can identify certain abnormal cells, including cells that may be associated with urothelial cancers.
Urine cytology is particularly useful for detecting high-grade urothelial abnormalities, although it has important limitations and cannot reliably detect every type of urinary tract cancer. For this reason, cytology is usually interpreted together with the patient’s symptoms, medical history, physical examination, and other diagnostic tests.
Because bladder cancer is one of the important conditions evaluated with urine cytology, understanding how the test is used in this setting can be helpful. For a more detailed discussion, see our article on urine cytology for bladder cancer.
This article explains what urine cytology is, why it is performed, how the sample is collected and analyzed, what different results mean, how accurate the test is, and what may happen after an abnormal result.
What Is Urine Cytology?
Urine cytology is a type of cytological examination in which cells shed into the urine are collected and examined microscopically.
Cells from different parts of the urinary system can naturally detach and enter urine. These cells may originate from structures lined by epithelial tissue, particularly the urothelium that lines much of the urinary tract.
A laboratory professional examines the cells for changes in their size, shape, organization, and nuclear characteristics. These microscopic features can sometimes indicate inflammation, infection, cellular abnormalities, or malignancy.
Definition of Urine Cytology
The term cytology refers to the study of individual cells. Therefore, urine cytology literally means the microscopic examination of cells present in urine.
A urine cytology specimen is typically prepared in a laboratory so that urinary cells can be concentrated and examined under a microscope. Depending on the laboratory and collection method, different preparation techniques may be used.
The test is fundamentally different from a urine culture. A culture attempts to grow microorganisms responsible for infection, whereas urine cytology examines cells.
It is also different from a routine urinalysis, which provides information about the chemical and physical characteristics of urine and may identify blood cells, white blood cells, protein, glucose, crystals, and other components.
What Cells Can Be Found in Urine?
Normal urine can contain small numbers of cells. These may include:
- Urothelial cells, which originate from the lining of the renal pelvis, ureters, bladder, and part of the urethra.
- Squamous epithelial cells, which may originate from the lower urinary or genital tract and can sometimes indicate contamination of a specimen.
- Renal tubular cells, which originate from the kidney tubules and may be present in certain circumstances.
- Inflammatory cells, such as white blood cells.
- Red blood cells, particularly when bleeding occurs somewhere in the urinary tract.
The presence of cells does not automatically mean disease. Cytologists evaluate the appearance and quantity of the cells and interpret the findings in their clinical context.
We have a dedicated blog post if you need to learn more about epithelial cells in urine tested during urinalysis.
What Can Urine Cytology Detect?
Urine cytology is primarily used to identify abnormal urinary tract cells.
Depending on the specimen and disease, cytology may detect:
- High-grade urothelial abnormalities
- Some urothelial carcinomas
- Certain other malignant cells
- Cellular changes associated with inflammation
- Some infectious or reactive changes
Why Is Urine Cytology Done?
Urine cytology is not routinely required for every person undergoing urine testing. It is usually ordered when there is a specific clinical reason to examine urinary cells.
The decision to perform the test depends on symptoms, previous diagnoses, risk factors, physical findings, and results from other investigations.
Blood in the Urine (Hematuria)
One reason urine cytology may be considered is hematuria, which means blood is present in the urine.
Hematuria can have many causes, ranging from urinary tract infections and kidney stones to structural abnormalities and urinary tract cancers.
The presence of blood does not mean that a person has cancer. However, persistent or unexplained hematuria may require further evaluation.
Depending on the clinical situation, this evaluation can involve urinalysis, urine culture, imaging, cystoscopy, and sometimes urine cytology or other urine-based tests.
Investigating Urinary Tract Symptoms
Urine cytology may also be considered when a patient has persistent or unexplained urinary symptoms.
Symptoms involving the urinary tract can include:
- Blood in the urine
- Frequent urination
- Painful urination
- Urgency
- Difficulty urinating
- Pelvic discomfort
These symptoms are nonspecific and can occur with many conditions. Urine cytology alone cannot determine the cause of urinary symptoms.
Instead, it may provide additional information when a healthcare professional is investigating a suspected urinary tract abnormality.
Monitoring People With a History of Urinary Tract Cancer
Another important application of urine cytology is surveillance.
People who have previously been diagnosed with certain urinary tract cancers may undergo periodic evaluations to look for evidence of recurrence or persistent disease. Depending on the individual’s diagnosis and risk category, urine cytology can be used alongside procedures such as cystoscopy and other investigations.
Its role is particularly relevant for detecting high-grade urothelial disease.
How Is a Urine Cytology Test Performed?
The urine cytology process generally involves collecting a urine sample, transporting it appropriately to the laboratory, processing the specimen, and examining the cells microscopically.
The exact procedure can vary between healthcare facilities and laboratories.
Collecting the Urine Sample
Urine cytology commonly uses a clean-catch midstream urine specimen.
The patient is generally instructed to clean the genital area before collection and begin urinating before collecting the sample in a sterile container. This helps reduce contamination from cells and microorganisms originating outside the urinary tract.
It is important to follow the specific instructions provided by the laboratory or healthcare professional because collection requirements can differ.
Unlike some other urine tests, the first morning urine is not necessarily preferred for cytology in every situation. Some laboratories may recommend collecting samples later in the day because cells that remain in the bladder for a prolonged period may undergo degenerative changes.
Laboratory Processing of the Sample
Once the urine sample reaches the laboratory, it is processed to recover cells that are present in the specimen.
The laboratory may concentrate the cellular material and prepare it for microscopic examination. Depending on the laboratory, techniques such as centrifugation, cytocentrifugation, liquid-based cytology, or other preparation methods may be used.
The prepared specimen is then examined by a trained cytologist or pathologist.
The examiner evaluates cellular characteristics such as:
- Cell size
- Cell shape
- Nuclear size and appearance
- Nuclear-to-cytoplasmic ratio
- Chromatin characteristics
- Cellular organization
- Presence of abnormal or malignant features
The final report is interpreted using standardized cytological terminology.
How Many Urine Samples Are Needed?
The number of samples required depends on the reason for testing and the laboratory’s protocol.
Multiple specimens may sometimes be collected because urinary cell shedding can vary over time. Examining more than one specimen can increase the opportunity to identify abnormal cells.
If multiple samples are requested, it is important to collect and label each specimen according to the instructions provided.
Does Urine Cytology Require Special Preparation?
In most cases, urine cytology does not require extensive preparation.
Patients should follow the laboratory’s instructions regarding:
- Sample collection
- Timing
- Container type
- Transportation
- Storage
Patients should also inform their healthcare provider about recent urinary tract procedures, catheterization, infections, or other relevant circumstances because these factors can influence the appearance of urinary cells.
Urine Cytology Results and Their Meaning
Urine cytology reports can use several different categories to describe the findings. The terminology may vary slightly between laboratories.
A result should always be interpreted in conjunction with the patient’s clinical history and other diagnostic findings.
Negative for Malignant Cells
A result reported as negative for malignant cells generally means that the examiner did not identify cancerous cells in the submitted specimen.
This is reassuring, but it does not necessarily mean that there is no urinary tract cancer.
A tumor may not release enough abnormal cells into the urine to be detected. In addition, some low-grade tumors can contain cells that are difficult to distinguish from benign urothelial cells.
Therefore, a negative urine cytology result does not always eliminate the need for further investigation when symptoms or other findings remain concerning.
Atypical Cells
An atypical result means that some cells do not look completely normal but do not have enough characteristics to classify them as clearly malignant.
Atypical cells can occur for several reasons.
Possible explanations include:
- Inflammation
- Infection
- Irritation
- Recent instrumentation
- Stones
- Reactive cellular changes
- Other benign conditions
- An underlying neoplastic process
An atypical result therefore does not automatically mean cancer.
Depending on the clinical circumstances, a healthcare provider may recommend repeat cytology, additional urine testing, cystoscopy, imaging, or another diagnostic evaluation.
Suspicious for Malignancy
A report described as suspicious for malignancy means that the cells have concerning features, but the findings may not be sufficient for a definitive diagnosis.
This category generally requires additional clinical evaluation.
The next step depends on factors such as the patient’s symptoms, previous history, cytology findings, cystoscopy results, and imaging findings.
Positive for Malignant Cells
A positive cytology result indicates that malignant cells have been identified in the urine specimen.
This finding can be highly significant and usually requires further evaluation to determine the source of the abnormal cells and the extent of disease.
Urine cytology can identify malignant cells, but it does not necessarily show exactly where a tumor is located.
Additional procedures may therefore be necessary to identify the underlying lesion.
Unsatisfactory or Inadequate Sample
Sometimes a urine cytology specimen cannot be adequately interpreted.
This may occur because:
- Too few cells are present.
- The cells are poorly preserved.
- There is excessive blood or debris.
- The sample is contaminated.
- Technical problems affect specimen preparation.
An inadequate result does not necessarily indicate that anything is wrong with the urinary tract. It means that the specimen did not provide enough reliable information.
A repeat specimen may therefore be recommended.
Accuracy, Limitations, and What Happens After the Test
Understanding the strengths and limitations of urine cytology is essential when interpreting the test.
How Accurate Is Urine Cytology?
The diagnostic performance of urine cytology depends heavily on the type and grade of urinary tract disease.
One of its major strengths is its ability to identify high-grade urothelial abnormalities, where abnormal cells often have more pronounced microscopic changes.
However, sensitivity is generally lower for low-grade urothelial tumors because their cells may retain many features of normal urothelial cells.
This creates an important distinction:
A negative urine cytology result can be reassuring, but it does not completely exclude urinary tract cancer.
The test is generally more useful as part of a broader diagnostic or surveillance strategy than as an isolated test.
Factors That Can Affect the Result
Several factors can complicate urine cytology interpretation.
These include:
Urinary Tract Infection
Inflammation associated with infection can cause reactive changes in urinary cells. These changes can sometimes make interpretation more difficult.
Blood in the Urine
A heavily blood-contaminated specimen can make it harder to evaluate the relevant epithelial cells.
Recent Procedures or Instrumentation
Catheterization, cystoscopy, biopsies, or other urinary procedures can cause reactive cellular changes.
Poor Sample Quality
A specimen containing too few cells, excessive degeneration, or contamination may be difficult to interpret.
These factors are why cytology results should always be considered together with the patient’s clinical circumstances.
Other Tests Used With Urine Cytology
Healthcare professionals may combine urine cytology with other tests depending on the suspected condition.
These may include:
Urinalysis:
Provides information about blood, protein, glucose, leukocytes, nitrites, specific gravity, and other urinary characteristics.
Urine culture:
Used to identify microorganisms that may cause urinary tract infections.
Molecular urine tests:
Some laboratory tests detect genetic or molecular markers associated with urinary tract cancer.
Cystoscopy:
A procedure in which a clinician directly examines the inside of the bladder and urethra using a specialized instrument.
Imaging:
Ultrasound, computed tomography (CT), magnetic resonance imaging (MRI), or other imaging studies may be used to evaluate the urinary tract when clinically appropriate.
These tests answer different questions. A urine cytology test examines shed cells, while cystoscopy allows direct visualization of the bladder and imaging evaluates anatomical structures.
