What is the significance of atypical urothelial cells (UCs) on urine cytology?

From the Guidelines

The finding of atypical urothelial cells on urine cytology requires immediate follow-up evaluation as it may indicate a precancerous or cancerous condition of the urinary tract, with a positive/atypical urinary cytology having a sensitivity of 57.7% and specificity of 94.9% 1. When atypical cells are identified, patients should undergo cystoscopy (bladder examination) and upper tract imaging such as CT urography to rule out malignancy. The significance of atypical cells falls between normal and suspicious for cancer, representing cellular changes that cannot be definitively classified as benign or malignant. Approximately 10-20% of patients with atypical cells will eventually be diagnosed with urothelial carcinoma, with higher risk in those with hematuria, smoking history, or prior bladder cancer. Follow-up typically includes repeat urine cytology in 3-6 months and surveillance cystoscopy, with the frequency determined by risk factors. Atypical cells may result from inflammation, stones, recent instrumentation, or chemotherapy/radiation effects, which can cause reactive changes mimicking cancer. The pathologist's specific comments about the degree of atypia are important, as "atypical cells cannot exclude high-grade urothelial carcinoma" carries more concern than simply "atypical cells present" 1. Proper clinical correlation with patient history and risk factors is essential for appropriate management, and the use of molecular analyses and bladder tumour marker tests, such as UroVysion, may be helpful in reducing the need for unnecessary diagnostic evaluations in intermediate- and high-risk bladder cancer patients 1. It is also important to note that the utility of protein-based markers in this setting has not been well tested, but as with cytology, inflammation may also negatively impact their ability to predict response 1. In patients with persistent atypical cytology, further diagnostic procedures such as ureteroscopy with/without biopsy or interval cystoscopy may be necessary 1. Overall, the management of atypical urothelial cells on urine cytology requires a comprehensive approach, taking into account the patient's history, risk factors, and the results of diagnostic tests, to ensure timely diagnosis and treatment of potential bladder cancer.

From the Research

Significance of Atypical Urothelial Cells

The presence of atypical urothelial cells in urine cytology is a significant finding that can indicate an increased risk of urothelial carcinoma.

• Atypical urothelial cells are defined as cells with nuclear abnormalities that do not meet the criteria for a definitive diagnosis of malignancy 2.
• The diagnosis of atypical urothelial cells can be subclassified into different categories, including "atypical urothelial cells of undetermined significance" (AUC-US) and "atypical urothelial cells cannot exclude high grade" (AUC-H) 2, 3.

Predictive Value of Atypical Urothelial Cells

The predictive value of atypical urothelial cells for urothelial carcinoma is a topic of ongoing research.

• Some studies have found that the presence of atypical urothelial cells is associated with an increased risk of urothelial carcinoma, particularly high-grade tumors 4, 3.
• Other studies have found that the subdivision of atypical urothelial cells into different categories does not improve diagnostic accuracy 5, 6.
• Certain cytomorphologic parameters, such as increased nuclear-cytoplasmic ratio and coarse chromatin, have been identified as predictive of high-grade urothelial carcinoma 2.

Clinical Implications

The clinical implications of atypical urothelial cells in urine cytology are significant.

• Patients with atypical urothelial cells may require close follow-up and further evaluation, including cystoscopy and biopsy 4, 3.
• The use of standardized terminology, such as AUC-US and AUC-H, can help to convey the risk of progression to high-grade tumors and guide clinical management 3.