Optimizing UroVysion Fluorescence In-Situ Hybridization Reflex Testing in Atypical Urothelial Cell Diagnosis: A Comprehensive Cytomorphological Analysis.

Objective: Urinary cytology is a key diagnostic tool for evaluating suspected urinary tract carcinoma, primarily high-grade urothelial carcinoma. The Paris System for Reporting Urinary Cytology (TPS), introduced in 2016, aimed to standardize reporting, though challenges with subjectivity and variability in diagnosing Atypical Urothelial Cells (AUCs) persist.

Methods: This retrospective study explored the correlation between cytomorphological features in "atypical" diagnosis and UroVysion fluorescence in-situ hybridization (U-FISH) results. We assessed 19 cytomorphologic parameters in 121 cases. Histologic diagnosis, clinical findings, and patient history were also documented.

Results: Of 121 cases, 38 (31.4%) tested U-FISH positive. The sensitivity and specificity of U-FISH in detecting malignancy were 93.5% and 91.1%, respectively. Five cytologic parameters-high atypical cellularity, nuclear/cytoplasmic ratio ≥0.7, nuclear enlargement (≥2.5 times), multinucleation, and mitosis-were significantly associated with U-FISH positivity. No association was found between TPS AUC criteria and U-FISH positivity. The majority of combinations of these key parameters exhibited high PPVs (>65.0%), suggesting their potential for classifying cases without U-FISH.

Conclusions: Cases exhibiting combinations of these five parameters or any four including mitosis demonstrated a 100% positive predictive value (PPV). However, subsets of cases with certain parameter combinations showed moderate PPVs, indicating the potential utility of reflex U-FISH testing.