title: Cuplike nuclei (prominent nuclear invaginations) in acute myeloid leukemia are highly associated with FLT3 internal tandem duplication and NPM1 mutation.
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.
authors: Department of Pathology, The University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, USA.
authors: Weina
authors: W
authors: Chen
authors: Sergej
authors: S
authors: Konoplev
authors: L Jeffrey
authors: LJ
authors: Medeiros
authors: Hartmut
authors: H
authors: Koeppen
authors: Vasiliki
authors: V
authors: Leventaki
authors: Saroj
authors: S
authors: Vadhan-Raj
authors: Dan
authors: D
authors: Jones
authors: Hagop M
authors: HM
authors: Kantarjian
authors: Brunangelo
authors: B
authors: Falini
authors: Carlos E
authors: CE
authors: Bueso-Ramos
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002467:Cell Nucleus / Q000235:genetics / Q000473:pathology*; D005260:Female; D020440:Gene Duplication; D006801:Humans; D016130:Immunophenotyping; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D000090243:Nucleophosmin; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics*
chemical_list: C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D000090243:Nucleophosmin; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3