Classification of acute myeloid leukemia by the revised fourth edition World Health Organization criteria: a retrospective single-institution study with appraisal of the new entities of acute myeloid leukemia with gene mutations in NPM1 and biallelic CEBPA

Abstract

The 2016/2017 World Health Organization (WHO2016/2017) classification for acute myeloid leukemia (AML) includes new entities with gene mutations in NPM1 (AML-NPM1mut) and biallelic CEBPA (AML-biCEBPAmut). To retrospectively identify and study these new molecularly defined WHO2016/2017entities, we reviewed clinicopathologic data and pretherapy archived pathologic materials at diagnosis for 143 consecutive AML cases (55.2% male, median age 62 [range 18-89] years) and classified all cases by the 2008 WHO (WHO2008) and revised WHO2016/2017 criteria. By WHO2008, cases included 21 (15%) with recurrent genetic abnormalities (52.3% male, median age 54 [range 18-82] years), 54 (38%) with myelodysplasia-related changes (57.4% male, median age 65 [range 32-84] years), 3 (2%) therapy related (100% male, median age 66 [range 32-84] years), and 65 (45%) not otherwise specified (52.3% male, median age 61 [range 19-89] years). Twenty-two (15.4%) cases (21 AML, not otherwise specified; 1 AML with myelodysplasia-related changes by WHO2008) reclassified by WHO2016/2017 as AML-NPM1mut showed female predominance (54.5%), and median (range) values were as follows: age 60.5 (23-84) years, hemoglobin 8.6 (5.6-12.9) g/dL, total leucocytes 30.1 (2.58-241.84) × 109/L, monocytes 1.65 (0-49.34) × 109/L, neutrophils 1.96 (0-29.79) × 109/L, platelets 55 (11-320) × 109/L, blasts (peripheral blood 41% [2%-98%], bone marrow 66% [17%-97%]), with myeloblastsCD34neg (17 [77%]/21), cytogeneticsnormal (20 [91%]/22), FLT3-ITDpos (9 [41%]/22), FLT3-ITDnegFLT3-TKDpos (5 [23%]/22), FLT3-ITDnegFLT3-TKDneg (8 [36%]/22), and extramedullary involvement (6 [27%]/22), including 1 novel cutaneous presentation. Notably, presenting features among AML-NPM1mut included those of anemia (22 [100%]) and thrombocytopenia (20 [91%]/22). This is also the first report of 4 [18%]/22 AML-NPM1mut (including 3 [75%]/4 nonsmokers) with a family history of leukemia and one 74-year-old with familial AML-biCEBPAmut. This study validates the application of the WHO2016/2017 classification criteria by retrospectively identifying AML-NPM1mut and AML-biCEBPAmut cases using single-gene molecular analyses. Additional studies are needed to characterize the complete spectrum of WHO2016/2017-defined AML-biCEBPAmut and for familial AML including AML-NPM1mut.