Jakovic, Ljubomir (21742748500)Ljubomir (21742748500)JakovicDjordjevic, Vesna (57215460423)Vesna (57215460423)DjordjevicKraguljac Kurtovic, Nada (37037758700)Nada (37037758700)Kraguljac KurtovicVirijevic, Marijana (36969618100)Marijana (36969618100)VirijevicMitrovic, Mirjana (54972086700)Mirjana (54972086700)MitrovicTrajkovic, Lazar (59347542100)Lazar (59347542100)TrajkovicVidovic, Ana (6701313789)Ana (6701313789)VidovicBogdanovic, Andrija (6603686934)Andrija (6603686934)Bogdanovic2025-06-122025-06-122024https://doi.org/10.3390/medicina60091443https://www.scopus.com/inward/record.uri?eid=2-s2.0-85205253640&doi=10.3390%2fmedicina60091443&partnerID=40&md5=106ea14eef4c8df2870cd31f677eb4bfhttps://remedy.med.bg.ac.rs/handle/123456789/929Background and Objectives: With the advent of novel therapies for nucleophosmin gene (NPM1)-mutated acute myeloid leukemia (AML), there is a growing need for the reliable prediction of NPM1 mutations. This study explored the role of cytomorphological features in the early prediction of NPM1-mutated AML. Materials and Methods: Altogether, 212 de novo AML cases with normal karyotypes, diagnosed and treated at a single institution within 5 years (2018–2023), were retrospectively evaluated. A final diagnosis of NPM1-mutated AML, based on the World Health Organization (WHO) integrated criteria, including real-time based identification of NPM1 mutation and normal karyotype, was established in 83/212 (39.15%) cases. Results: Cup-like blasts (CLBs), a cytomorphological feature suggestive of NPM1-mutated AML, were detected in 56/83 (67%) patients. Most cases (44/56, 78.6%) had CLB ≥ 10%. In total, 27 of 83 AML NPM1-mutated patients had no CLB morphology (missed call). Additionally, two of 212 had CLB morphology without confirmed NPM1 mutation (wrong call). The positive/negative predictive values of cytomorphological evaluation for CLB ≥ 10% were 95.7%/75.6%, with sensitivity/specificity of 53%/98.5%, while the accuracy was 80.7%. We noted an increased percentage of CLBs (≥15%) in 77.8% and 50% of patients with AML without and with granulocytic maturation, respectively (the specificity for NPM1 mutation prediction was 100%). CLB was associated with fms-like tyrosine kinase 3 (FLT3) mutation (p = 0.03), but, without statistical significance for CLB ≥ 10% and CLB ≥ 15%. Conclusions: Our investigation confirmed that the morphological identification of CLB at diagnosis represents a reliable and easily reproducible tool for the early prediction of NPM1 mutations, enabling a streamlined genetic work-up for its confirmation. This may facilitate considering the early administration of individualized therapies by clinicians for specific patients. © 2024 by the authors.acute myeloid leukemiacup-like blastNPM1 mutation