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  • Title: Cuplike nuclei (prominent nuclear invaginations) in acute myeloid leukemia are highly associated with FLT3 internal tandem duplication and NPM1 mutation.
    Author: Chen W, Konoplev S, Medeiros LJ, Koeppen H, Leventaki V, Vadhan-Raj S, Jones D, Kantarjian HM, Falini B, Bueso-Ramos CE.
    Journal: Cancer; 2009 Dec 01; 115(23):5481-9. PubMed ID: 19672946.
    Abstract:
    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: >or=10% blasts with nuclear invaginations in >or=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.
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