Cancer cytopathology · 2025
Neutrophil-calibrated atypical squamous cells in ThinPrep urine cytology for detecting squamous differentiation in urothelial carcinoma.
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Furuhata Ayako, Teramoto Yuki, Minamiguchi Sachiko, Hirata Masahiro, Haga Hironori
Аннотация
BACKGROUND: Urothelial carcinoma with squamous differentiation (UCSD) carries adverse outcomes, yet cytological recognition is challenging because keratinized atypical squamous cells (ASCs) often show deceptively low nuclear-to-cytoplasmic ratios. A size-based ASC classification anchored to neutrophils was evaluated as a biological internal reference.
METHODS: All cytology specimens were prepared with the ThinPrep liquid-based cytology system. Seventeen urine cytology specimens from histologically confirmed UCSD and 79 cytologically benign (BE) specimens with squamous cells were retrospectively reviewed. ASCs with orangeophilic cytoplasm were subclassified by nuclear size relative to the adjacent neutrophils: ASC-S (small nuclei; >1× neutrophil) and ASC-L (large nuclei; >2× neutrophil). Counts were obtained from five high-power fields. UCSD was stratified by the extent of squamous differentiation (<50% vs. ≥50%).
RESULTS: No ASC-S/L was identified in BE specimens, whereas either subtype was present in 15 of the 17 UCSD cases, which yielded a cohort-level sensitivity of 88% and specificity of 100% for UCSD detection (95% CI, 65.7%-96.7% and 95.4%-100%, respectively). ASC-S was more prevalent than ASC-L, and was observed across Paris System categories-including atypical urothelial cells (AUCs)-whereas ASC-L appeared mainly in suspicious for high-grade urothelial carcinoma/high-grade urothelial carcinoma. ASC-S counts tended to increase with greater histological squamous differentiation, and were detectable even when tissue involvement was <50%.
CONCLUSIONS: Neutrophil-calibrated ASC classification provides an objective, biologically grounded framework that aligns cytology with histology in UCSD. Reporting ASC-S/L-particularly ASC-S in equivocal (AUC) specimens-may facilitate earlier recognition of squamous differentiation and inform subsequent tissue evaluation. Prospective, multi-institutional validation with interobserver agreement and receiver operating characteristic-based thresholds is warranted.
METHODS: All cytology specimens were prepared with the ThinPrep liquid-based cytology system. Seventeen urine cytology specimens from histologically confirmed UCSD and 79 cytologically benign (BE) specimens with squamous cells were retrospectively reviewed. ASCs with orangeophilic cytoplasm were subclassified by nuclear size relative to the adjacent neutrophils: ASC-S (small nuclei; >1× neutrophil) and ASC-L (large nuclei; >2× neutrophil). Counts were obtained from five high-power fields. UCSD was stratified by the extent of squamous differentiation (<50% vs. ≥50%).
RESULTS: No ASC-S/L was identified in BE specimens, whereas either subtype was present in 15 of the 17 UCSD cases, which yielded a cohort-level sensitivity of 88% and specificity of 100% for UCSD detection (95% CI, 65.7%-96.7% and 95.4%-100%, respectively). ASC-S was more prevalent than ASC-L, and was observed across Paris System categories-including atypical urothelial cells (AUCs)-whereas ASC-L appeared mainly in suspicious for high-grade urothelial carcinoma/high-grade urothelial carcinoma. ASC-S counts tended to increase with greater histological squamous differentiation, and were detectable even when tissue involvement was <50%.
CONCLUSIONS: Neutrophil-calibrated ASC classification provides an objective, biologically grounded framework that aligns cytology with histology in UCSD. Reporting ASC-S/L-particularly ASC-S in equivocal (AUC) specimens-may facilitate earlier recognition of squamous differentiation and inform subsequent tissue evaluation. Prospective, multi-institutional validation with interobserver agreement and receiver operating characteristic-based thresholds is warranted.