The term “reactive” is a descriptive finding that does not signify cancer. Urothelial cells form the urothelium, the specialized, multi-layered lining of the urinary tract, including the bladder, ureters, and renal pelvis. This lining acts as a barrier, preventing toxic urine components from seeping into the underlying tissue. When a pathologist identifies reactive changes, they are observing a benign, temporary response by these cells to some form of irritation or injury.
Understanding Urothelial Cells and Reactivity
The urothelium is a dynamic tissue, designed to stretch and contract as the bladder fills and empties. Urothelial cells are constantly shedding into the urine, which is why they are present in urine cytology samples. When irritated, these cells may enlarge, multiply, and show minor alterations in their internal structures. The changes are considered orderly and uniform across the affected cells, reflecting a coordinated biological defense mechanism.
Common Triggers for Reactive Changes
Reactive changes in urothelial cells are typically linked to inflammation or physical trauma within the urinary tract. The most frequent causes of this irritation include:
- Urinary tract infection (UTI), where the presence of bacteria and the resulting immune response directly irritate the urothelium.
- Kidney or bladder stones (calculi), which cause mechanical friction as they move or sit within the urinary tract, physically damaging the urothelial lining.
- Recent medical procedures, such as catheterization, cystoscopy, or other instrumentation, which can induce temporary reactive changes.
- Certain medications, like the chemotherapy drug cyclophosphamide, which can cause chemical cystitis that results in urothelial irritation.
Differentiating Reactive Cells from Malignancy
The primary method for a pathologist to distinguish a reactive change from a true malignancy is through a detailed examination of the cell morphology. Reactive cells exhibit a low nuclear-to-cytoplasmic (N/C) ratio, which is a measurement of the nucleus size compared to the entire cell size. This ratio is typically maintained in reactive cells because the cytoplasm, the substance surrounding the nucleus, often enlarges alongside the nucleus.
In contrast, malignant cells, especially high-grade urothelial carcinoma, display a significantly high N/C ratio, meaning the nucleus is disproportionately large relative to the cell’s total size. Reactive cell nuclei usually maintain a smooth, round, or oval contour, and the internal genetic material, the chromatin, remains finely granular and evenly dispersed. Malignant cells, however, show irregular, jagged nuclear membranes and chromatin that is coarse, clumpy, or hyperchromatic, giving the nucleus a dark, disorganized appearance.
Reactive cells may show prominent nucleoli, which is a common sign of increased metabolic activity due to inflammation, not a sign of cancer. The changes seen in reactive cells are generally uniform across the sample, whereas cancerous cells are characterized by marked pleomorphism, meaning a significant variation in cell size and shape. The presence of a clean background, often alongside numerous inflammatory white blood cells, also favors a benign reactive process over a malignant one.
Clinical Management and Follow-Up
The finding of reactive urothelial cells in a cytology report often leads to a practical clinical approach focused on resolving the underlying irritation. If a urinary tract infection or stone is present, the initial step involves appropriate treatment, such as antibiotics or procedures to manage the stone. In many cases, once the underlying cause is resolved, the reactive changes disappear.
For patients without an obvious cause of irritation, or for those with persistent or recurring reactive features, the physician may recommend a repeat cytology test after a period of time. This re-evaluation helps confirm the reversible nature of the cellular changes. The finding of “reactive” cells alone does not carry a significantly increased risk of urothelial cancer compared to a benign finding.
If the reactive changes are accompanied by other concerning symptoms, such as persistent blood in the urine, or if the cytology report uses the term “atypical, favoring reactive,” further investigation may be warranted. This can include imaging tests, such as a CT urogram, or a cystoscopy, where a small camera is used to visually inspect the bladder lining. Cystoscopy remains the standard for ruling out any visible tumors, especially since cytology has a lower sensitivity for detecting low-grade lesions.