Cuplike nuclei (prominent nuclear invaginations) in acute myeloid leukemia are highly associated with FLT3 internal tandem duplication and NPM1 mutation

BACKGROUND: A small subset of patients with acute myeloid leukemia (AML) have cuplike nuclei. Other investigators have demonstrated that these neoplasms have distinctive clinicopathologic and molecular features. METHODS: The authors searched for patients who had AML with cuplike nuclei at their institution over a 10-year interval. A strict definition for cuplike nuclei was used: ≥10% blasts with nuclear invaginations in ≥25% of the nuclear area. The relevant data were reviewed, and the results were compared with a control group of patients who had AML without cuplike nuclei. RESULTS: In total, 22 patients who had AML with cuplike nuclei were identified and were classified as AML without maturation (French-American-British classification M1) (AML M1). Compared with the control group (AML M1), patients who had AML with cuplike nuclei were associated significantly with fms-like tyrosine kinase 3 (FLT3)-internal tandem duplication (ITD) (86% vs 38%, respectively; P=.002); nucleophosmin 1 (NPM1) mutations (86% vs 19%; P < .0001); both mutations (77% vs 14%; P < .0001); normal karyotype (86% vs 40%; P=.003); bone marrow blast count (90% vs 84%; P=.016); myeloperoxidase positivity (95% vs 30% blasts; P=.001); higher D-dimer levels (>5000 ng/mL vs 569 ng/mL; P=.001); and the absence of CD7 (91% vs 52%; P=.007), CD34 (82% vs 5%; P < .0001), and human leukocyte antigen, D-related (59% vs 10%; P=.001). There were no differences in age, sex, or peripheral blood counts. The positive predictive value of recognizing AML with cuplike nuclei for FLT3-ITD, NPM1, and both mutations was 81%, 86%, and 77%, respectively. CONCLUSIONS: Cuplike nuclei in AML were highly associated with the presence of NPM1 and FLT3-ITD mutations and with several clinicopathologic and immunophenotypic features. Recognition of the distinctive morphologic features of AML with cuplike nuclei may be helpful in streamlining the workup of these neoplasms.