We studied whether atypical, non-superficial urothelial cells (AUC) could be separated into new subcategories including AUC 'of undetermined significance' (AUC-US) and 'cannot exclude high grade'' (AUC-H) in order to help to standardize urine cytopathology reports, as it is widely accepted in the Bethesda system for gynaecological cytopathology. We investigated whether AUC-US and AUC-H, defined by distinctive cytological criteria, might be separated with statistical significance according to actual diagnosis and follow-up data. A series of 534 cyto-histological comparisons taken in 139 patients, including 221 AUC at various steps of their clinical history was studied. There were 513 (96.1%) postcystoscopy and 469 (87.8%) ThinPrep® liquid-based specimens (95.9% and 89.1% of AUC cases, respectively). Patients viewed between 1999 and 2011 had histological control in a 0- to 6-months delay and were followed-up during an additional 5.9±9.2 (0- to 56-) months period. The 221 AUC represented 0.8-2% of the specimens viewed during the study period. Among AUC-H cases, 70 out of 185 (37.8%) matched with high-grade lesions, compared with 3 of 38 (8.3%) of AUC-US cases (P=0.0003). Conservatively treated patients with AUC-H more frequently developed high-grade lesions than those with AUC-US (54.1% versus 16.7%, P=0.0007) with a 17.6-months mean delay. Nuclear hyperchromasia, a nuclear to cytoplasm (N/C) ratio>0.7 and the combination of both were the more informative diagnostic criteria, all with P<0.01. We conclude that the new subcategories could help to standardize urine cytopathology reports and contribute to the patient's management, provided it is validated by multicentric studies.
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