A urine cytology test examines cells shed into urine to look for changes that suggest high-grade urothelial cancer, especially bladder cancer and carcinoma in situ. It is not the same as a routine urinalysis. A cytopathologist studies the cells under a microscope and reports whether they look benign, atypical, suspicious, or malignant. Modern laboratories commonly use standardized terminology based on the Paris System for Reporting Urinary Cytology.
Urine cytology is most useful for detecting high-grade urothelial carcinoma. It is much less sensitive for low-grade bladder tumors, so a negative result does not rule out cancer. An “atypical” result also does not mean cancer is present; inflammation, stones, instrumentation, treatment effects, and cellular degeneration can create abnormal-looking cells. When cytology is abnormal, the next step depends on the exact category, symptoms, cystoscopy findings, prior cancer history, and whether the sample came from voided urine or directly from the urinary tract.
- What it looks for: abnormal urothelial cells shed from the bladder, ureters, renal pelvis, or urethra.
- Best use: detecting high-grade urothelial carcinoma and carcinoma in situ; it performs poorly for many low-grade tumors.
- Atypical cells: are not a cancer diagnosis and can result from inflammation, stones, treatment, instrumentation, or true neoplasia.
- Negative result: means no convincing high-grade cancer cells were seen, but bladder cancer can still be present.
- Positive or suspicious result: usually requires urologic evaluation, often including cystoscopy and investigation of the urinary tract.
Table of Contents
- What urine cytology is
- Why urine cytology is ordered
- Collection and sample quality
- Urine cytology result categories
- What atypical urothelial cells mean
- Accuracy and limitations
- Follow-up after an abnormal result
What urine cytology is
Urine cytology is a microscopic examination of cells that have entered the urine from the lining of the urinary tract. Most bladder cancers arise from urothelial cells, the specialized cells that line the bladder and much of the collecting system. Tumor cells can detach and appear in a urine sample, where a cytopathologist evaluates their size, nuclear features, chromatin pattern, cell clusters, degeneration, and other characteristics.
The test is designed primarily to identify high-grade urothelial carcinoma (HGUC). High-grade tumors have more pronounced cellular abnormalities and are therefore easier to recognize cytologically. Low-grade tumors often shed cells that look relatively bland, which is why a normal cytology result cannot reliably exclude a small or low-grade bladder tumor.
Urine cytology differs from several other urinary cancer tests. BTA testing measures tumor-associated proteins rather than cell appearance. UroVysion FISH looks for selected chromosome abnormalities within urinary cells. Newer gene-expression and DNA-based assays measure molecular changes. Cytology remains valuable because it evaluates the cells directly and is particularly specific when convincing high-grade malignant features are present.
A positive voided urine cytology result does not necessarily identify the exact location of the tumor. Abnormal cells can originate from the bladder, ureters, renal pelvis, or urethra. The urologist must therefore interpret the result in the context of cystoscopy and upper urinary tract imaging.
Cytology is not the same as biopsy pathology
Cytology answers a narrower question than a tissue biopsy. The cytologist sees individual cells and small groups that have exfoliated into urine, but usually cannot assess how deeply a tumor has invaded the bladder wall or determine the full architecture of a lesion. A transurethral resection or biopsy preserves tissue relationships and allows the pathologist to assign tumor type, grade, and—when enough tissue is present—whether the cancer invades the lamina propria or muscularis propria.
That distinction explains why even a report that is clearly positive for high-grade urothelial carcinoma is typically followed by cystoscopy and tissue sampling. Cytology can provide a strong warning signal, but treatment decisions such as intravesical therapy, repeat resection, or cystectomy depend on the tissue diagnosis and clinical stage. It also explains why a low-grade papillary tumor seen on cystoscopy may coexist with a “negative for high-grade urothelial carcinoma” cytology report without creating a contradiction: the cytology terminology is intentionally focused on high-grade disease.
Why urine cytology is ordered
Clinicians most often order urine cytology when there is concern for urothelial carcinoma or when a patient with known bladder cancer is being monitored. It may be part of the evaluation of visible blood in the urine, selected cases of persistent microscopic hematuria, suspicious urinary symptoms, or follow-up after treatment for non-muscle-invasive bladder cancer.
Cytology can be especially helpful when the clinical concern is carcinoma in situ (CIS). CIS is a flat, high-grade lesion that can be difficult to recognize on standard imaging and may be subtle on cystoscopy. Because CIS cells can have striking malignant features, cytology may add important evidence when cystoscopy is negative or equivocal.
However, cytology is not recommended as a universal screening test for everyone with microscopic blood in the urine. Modern hematuria guidelines use risk-based evaluation. Depending on age, smoking exposure, degree of hematuria, and other factors, cystoscopy and imaging may be more important than routine cytology.
Common reasons for ordering urine cytology include:
- visible hematuria with concern for urinary tract malignancy;
- persistent microscopic hematuria in selected higher-risk patients;
- irritative voiding symptoms with concern for CIS;
- surveillance after a previous high-grade bladder tumor;
- abnormal cystoscopy requiring additional information;
- evaluation of the upper urinary tract using selectively collected urine or washings.
Cytology should not replace cystoscopy when cystoscopy is indicated. A bladder tumor can be present even when no malignant cells are seen in the urine.
Collection and sample quality
Urine cytology can be performed on naturally voided urine or on samples collected during a urologic procedure. The source matters because cellularity and interpretation can differ.
For routine voided cytology, laboratories commonly prefer a freshly voided sample collected after the first morning urination, because cells that remain in the bladder overnight may become degenerated. Exact instructions vary, so patients should follow the collection directions from the laboratory. Some evaluations use more than one sample collected on different days because shedding can be intermittent.
A midstream clean-catch technique may be requested to reduce contamination, although the priorities for cytology are not identical to those for urine culture. The specimen should be delivered or preserved according to laboratory instructions so cells do not deteriorate before processing.
Samples can also come from bladder washings, catheterized urine, ureteral washings, or renal pelvis specimens. Instrumented samples may contain more cells but can also show reactive changes caused by manipulation.
Reasons a sample may be difficult to interpret
Low cellularity, severe degeneration, blood, inflammation, urinary tract infection, stones, recent procedures, and intravesical treatments can all complicate interpretation. Bacillus Calmette-Guérin (BCG) therapy and other bladder treatments can produce striking reactive cellular changes. Viral infections such as polyomavirus can also create atypical-appearing cells.
A report may be labeled nondiagnostic or unsatisfactory when there are too few well-preserved cells to make a meaningful assessment. That is not the same as a negative result. The clinician may repeat the sample or proceed with other testing based on the clinical concern.
When a specimen is too scant or degraded for confident interpretation, repeating the sample can be more informative than assigning meaning to an inadequate preparation. A new specimen provides a fresh population of shed cells and may reduce uncertainty caused by collection or preservation problems.
Urine cytology result categories
The Paris System was developed to standardize urine cytology and emphasize the detection of high-grade urothelial carcinoma. The second edition, published in 2022, refined terminology and criteria. Laboratories may use slightly different wording, but the major concepts are similar.
| Typical report category | What it means | General implication |
|---|---|---|
| Nondiagnostic / unsatisfactory | Not enough suitable cellular material for reliable interpretation | May need repeat sampling or another test |
| Negative for high-grade urothelial carcinoma | No convincing high-grade malignant cells seen | Reassuring for high-grade disease, but does not exclude low-grade cancer |
| Atypical urothelial cells | Cells have some abnormal features but do not meet criteria for suspicious or malignant | Clinical context and follow-up determine significance |
| Suspicious for high-grade urothelial carcinoma | Features raise substantial concern but are insufficient for a definitive HGUC call | Usually prompts further urologic evaluation |
| High-grade urothelial carcinoma | Cells show convincing malignant features | Strong evidence requiring localization and tissue confirmation |
The phrase “negative for high-grade urothelial carcinoma” is deliberate. It does not mean “negative for every possible bladder tumor.” Low-grade papillary tumors may be present even when cytology is negative because their shed cells often resemble normal urothelial cells.
Some laboratories may also report other malignant cell types when present. Squamous cell carcinoma, adenocarcinoma, prostate cancer involving the urinary tract, or metastatic malignancy can sometimes shed cells into urine, although these are less common contexts.
What atypical urothelial cells mean
“Atypical urothelial cells” is an indeterminate category, not a cancer diagnosis. The pathologist has identified cells that are more abnormal than expected but do not meet the threshold for “suspicious” or “high-grade urothelial carcinoma.”
Atypia can occur because of true neoplasia, but also because cells have been irritated or damaged. Common benign explanations include infection, urinary stones, recent cystoscopy or catheterization, radiation, intravesical therapy, and cellular degeneration. This is why an isolated atypical result is interpreted differently from repeated atypia in a person with prior high-grade bladder cancer.
Published series using the Paris System show that the risk of finding high-grade malignancy rises as the category progresses from negative to atypical to suspicious to HGUC. A 2022 meta-analysis estimated a pooled risk of high-grade malignancy of about 39% in the atypical category, but that number should not be applied as a personal probability. The studies included different populations and verification methods, and more recent second-edition experience reports a broad risk range.
A practical interpretation is:
- One atypical result with an obvious benign explanation may be repeated after the cause resolves.
- Persistent atypia without a clear benign cause deserves closer assessment.
- Atypia plus visible hematuria, abnormal cystoscopy, or prior high-grade cancer is more concerning.
- A suspicious or malignant cytology result generally requires prompt evaluation even if the bladder looks normal on an initial exam.
The exact wording in the pathology report matters. “Atypical,” “suspicious,” and “positive for high-grade urothelial carcinoma” are not interchangeable categories.
Accuracy and limitations
Urine cytology is known for high specificity but uneven sensitivity. Current European guidance cites sensitivity around 84% for high-grade/G3 tumors and about 16% for low-grade/G1 tumors in the evidence it summarizes, while individual studies vary considerably. Sensitivity for carcinoma in situ also varies because lesion size, shedding, sample quality, and interpretation differ.
Specificity in experienced hands often exceeds 90% for high-grade disease, which means a clearly malignant result is meaningful. The tradeoff is that many low-grade tumors are missed.
The test also has a sampling limitation: a tumor has to shed enough recognizable cells into the particular specimen that reaches the laboratory. A small lesion may be present while the collected urine contains few or no diagnostic cells. This is one reason a series of samples can sometimes increase yield, although repeated cytology still cannot substitute for direct inspection of the bladder when cystoscopy is indicated.
Another source of confusion is that the report may mention red blood cells, inflammation, crystals, or organisms in addition to the cytologic category. Those observations can help explain atypia but should not be treated as a complete urinalysis or urine culture unless those tests were separately performed. When infection is suspected, a clinician may order culture and repeat cytology after treatment, but persistent hematuria or cancer risk still needs its own evaluation.
For surveillance, trends in wording can be informative. A shift from repeatedly negative specimens to persistent atypical or suspicious findings deserves attention, especially after high-grade disease. Still, the change should be confirmed within the whole clinical picture rather than interpreted as a laboratory “tumor level” rising over time. Cytology is categorical and morphology-based, not a quantitative tumor-marker concentration.
Several factors influence performance:
- Tumor grade: high-grade cancers shed more obviously malignant cells.
- Tumor size and location: small lesions or upper tract tumors may shed fewer cells into a voided specimen.
- Sample quality: poorly preserved or sparsely cellular urine reduces sensitivity.
- Inflammation and treatment: reactive atypia can create false-positive or indeterminate results.
- Observer variability: cytology requires expert visual interpretation.
This is why cytology and cystoscopy complement each other. Cystoscopy can directly visualize papillary tumors that cytology misses, while cytology may flag a high-grade flat lesion that is subtle during cystoscopy.
Molecular tests can add information when cytology is equivocal. UroVysion is sometimes used after atypical cytology or in selected surveillance situations. NMP22, BTA, and newer transcript or methylation assays are other examples, but none should be assumed to replace standard evaluation simply because it is noninvasive.
Why “negative” can still require follow-up
A negative cytology result becomes less reassuring when pretest risk is high. Visible hematuria, a strong smoking history, abnormal imaging, a suspicious bladder lesion, or a history of high-grade urothelial cancer can justify cystoscopy and other evaluation despite negative cytology. The test result changes probability; it does not erase the clinical indication for workup.
Conversely, repeatedly abnormal cytology with normal cystoscopy raises a different question: whether malignant cells are coming from a flat bladder lesion that was not seen, the prostatic urethra in a man, or the upper urinary tract. The urologist may use enhanced cystoscopy, directed biopsies, upper-tract imaging, ureteroscopy, or molecular testing depending on the situation.
Follow-up after an abnormal result
Follow-up is based on the exact category rather than the general phrase “abnormal urine cytology.”
For nondiagnostic cytology, the clinician may repeat the specimen under better collection conditions. If symptoms or risk are already concerning, however, evaluation should not be delayed merely to obtain a better cytology sample.
For atypical cytology, the clinician looks for infection, stones, recent instrumentation, and prior treatment. Repeat cytology may be reasonable in a lower-risk situation. In a higher-risk patient, cystoscopy and imaging may be more important than waiting for a repeat sample.
For suspicious or positive high-grade cytology, prompt urologic evaluation is appropriate. Cystoscopy can identify visible bladder tumors, and tissue biopsy establishes the diagnosis. If cystoscopy does not explain a strongly positive cytology result, the rest of the urothelial tract may need assessment.
A positive result should also be distinguished from routine urinary symptoms. Burning, frequency, urgency, fever, and flank pain may indicate infection or another acute problem and should be evaluated clinically. Visible blood in the urine should be reported even when it occurs only once.
For people already under surveillance, the result must be interpreted within the risk category of the original tumor. A previous low-grade papillary tumor and a previous high-grade T1 tumor carry very different recurrence and progression risks. A urine test is most useful when it is integrated into that established surveillance plan.
When the laboratory calls a specimen unsatisfactory or limited, that is different from a true negative result. Too few urothelial cells, heavy blood or inflammation, degeneration, or poor preservation can prevent a confident interpretation. In that situation, a repeat specimen may be requested, but the timing and need for cystoscopy still depend on why testing was ordered and the patient’s underlying cancer risk.
References
- The Paris system for reporting urinary cytology: what worked and what still needs to be improved 2026 (Review)
- Pitfalls in Urinary Tract Cytopathology 2024 (Review)
- Diagnosis of Low-Grade Urothelial Neoplasm in the Era of the Second Edition of the Paris System for Reporting Urinary Cytology 2023
- The Paris System for Reporting Urinary Cytology: A Meta-Analysis 2022 (Meta-Analysis)
- Updates to Microhematuria: AUA/SUFU Guideline (2025) 2025 (Guideline)
- Implementation of The Paris System for Reporting Urine Cytology improves diagnostic accuracy of selective upper urinary tract cytology 2024
Disclaimer
This article is for general educational purposes and does not replace evaluation by a clinician or cytopathologist. Urine cytology cannot by itself confirm or exclude bladder or upper urinary tract cancer. Abnormal results, visible blood in the urine, or persistent concerning symptoms should be reviewed with a qualified healthcare professional.
