Real-World Evaluation of the Sysmex XN-9100 WDF-WPC Workflow: Diagnostic Performance, False-Negative Burden, and...

Background: Modern hematology analyzers integrate multiparametric technologies and adaptive flagging algorithms to support rapid detection of abnormal leukocyte populations. The Sysmex XN-9100 employs the White Blood Cell Differential (WDF) channel for first-line screening and the White Precursor Cell (WPC) channel as a reflex test for improved detection of blasts and abnormal lymphocytes. Although widely implemented, the real-world diagnostic performance and workflow implications of this integrated strategy remain incompletely characterized. Objectives: To evaluate, in a large real-world cohort, the performance of the Sysmex XN-9100 WDF-WPC workflow, focusing on its diagnostic accuracy, its capability to identify pathological cases within the WDF-negative population, and its potential implications for blood smear review workload optimization. Methods: A retrospective analysis was performed on 4531 consecutive routine blood samples reviewed between February and June 2025. All samples were analyzed using the Sysmex XN-9100. WDF-positive cases ("Blasts/Abnormal lymphocytes?") underwent reflex WPC testing ("Blasts?" and "Abnormal lymphocytes?"). Peripheral blood smear morphology, based on the evaluation of 200 leukocytes using the DI-60 digital imaging system, constituted the reference standard. Diagnostic performance metrics, including sensitivity, specificity, predictive values, likelihood ratios, accuracy, and ROC analysis, were calculated for WDF and WPC channels using both individual and aggregated flag evaluations. Results: The WDF-B/AL (White Blood Cell Differential Channel-"Blasts/Abnormal lymphocytes?") flag demonstrated high sensitivity (88.24%) and negative predictive value (92.73%), supporting its role as an effective first-line screening tool, although specificity was limited (48.87%; AUC = 0.75). Unlike most previous studies, our workflow allowed evaluation of pathological cases occurring within the WDF-negative population, providing a realistic estimate of the false-negative burden. Disaggregated WPC analysis revealed complementary diagnostic profiles: WPC-B (White Precursor Cell Channel-"Blasts?") showed higher specificity (77.71%) and overall discriminative performance (AUC = 0.81), whereas WPC-AL (White Precursor Cell Channel-"Abnormal lymphocytes?") achieved higher sensitivity (92.18%) and negative predictive value (95.99%). Aggregated evaluation of WPC flags (logical OR) maximized sensitivity (92.68%) and reduced false-negative cases, supporting the role of the WPC channel as a second-level diagnostic safety net. Furthermore, within the integrated laboratory workflow, WPC-negative results may support the optimization of manual smear-review allocation when interpreted together with predefined institutional smear-review criteria, while maintaining diagnostic safety. Conclusions: The Sysmex XN-9100 WDF-WPC workflow constitutes a multilayered high-sensitivity screening strategy that prioritizes abnormality detection while optimizing laboratory efficiency. The complementary behavior of WPC-B and WPC-AL enhances overall workflow safety, whereas evaluation of WDF-negative pathological cases provides a more realistic assessment of screening performance than conventional reflex-based studies. Beyond analytical accuracy, the workflow may contribute to balancing diagnostic reliability, patient safety, and resource utilization in high-volume laboratory practice.