Classification of acute myeloid leukemia by the revised 4th 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

Human Pathology - 5d ago Preview

 
 
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Publication date: Available online 8 May 2019

Source: Human Pathology

Author(s): Rina Kansal

Summary

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 pre-therapy archived pathologic materials at diagnosis for 143 consecutive AML cases {55.2% males, median age 62(range 18–89)y}, 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% males, median age 54(range18–82)y}, 54(38%) with myelodysplasia-related changes (AML-MRC) {M:F = 31:23, median age 65(range 32–84)y}, 3(2%) therapy-related {100% males, median age 66(range 32–84)y}, and 65(45%) not otherwise specified (AML-NOS) {M:F = 34:31, median age 61(range 19–89)y}. 22(15.4%) cases (21 AML-NOS, 1 AML-MRC by WHO2008) reclassified by WHO2016/2017 as AML-NPM1mut showed female predominance (54.5%), and median(range) values: age 60.5(23–84)y, hemoglobin 8.6(5.6–12.9)g/dL, total leucocytes 30.1(2.58–241.84)x109/L, monocytes 1.65(0–49.34)x109/L, neutrophils 1.96(0–29.79)x109/L, platelets 55(11–320)x109/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 non-smokers} 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.