Institution: Massachusetts General Hospital
Additional authors:Robert P. Hasserjian
Session: AML with recurrent genetic mutations Part II
HISTORY
A 68 year old man with no significant prior medical history presented with a five-week history of worsening fatigue, cough and headache, and had more recently developed a rash. On physical exam he was found to have a low grade fever and petechiae over his lower extremities. CBC revealed a WBC of 92 x 10^9/L and a platelet count of 14 x 10^9/L. A peripheral blood smear revealed 79% blasts with frequent Auer rods. A bone marrow biopsy and aspirate confirmed a diagnosis of acute myeloid leukemia. Cytogenetic and molecular studies revealed a normal karyotype, FLT3 wildtype, NPM1 wildtype, CEPBA mutated AML. He received induction chemotherapy with idarubicin and cytarabine. His day 14 marrow was ablated, and a bone marrow biopsy 34 days post induction was consistent with complete remission.
DETAILS
The diagnostic bone marrow biopsy was taken from the posterior iliac crest, fixed in B+, and decalcified before processing. The marrow cellularity was overall 85% with markedly decreased normal hematopoietic elements. Primitive cells consistent with blasts occurred in sheets and comprised approximately 75% of the cellularity. A 200-cell count of the bone marrow aspirate smear revealed 59% blasts. The blasts had round to slightly irregular nuclei, fine chromatin, prominent nucleoli and occasional cytoplasmic granules and Auer rods.
IMMUNOHISTOCHEMISTRY AND FLOW CYTOMETRY
Flow cytometry of the peripheral blood and bone marrow aspirate specimens revealed myeloid blasts with the following immunophenotype: CD33+ CD13-/+ MPO+ CD117+ CD34+ CD14- HLA-DR+ CD11c+/- CD64+/- CD4+/- CD7+/-.
CYTOGENETIC FINDINGS
Normal karyotype: 46[X,Y].
MOLECULAR FINDINGS
There were no FLT3-ITD or TKD mutations and no NPM1 mutation.
A heterozygous CEBPA mutation was identified (nucleotide change: 934-939dup; amino acid change: Q312K313dup). Additional mutational analysis for 90 loci in 23 common cancer genes revealed no additional mutations.INTERESTING FEATURES
CEBPA mutations are associated with a favorable prognosis in the context of a normal karyotype and lack of a FLT3-ITD mutation. Therefore, mutational analysis in patients with normal karyotype AML may be important in guiding treatment strategies and predicting outcome. AML with mutated CEBPA is currently a provisional category in the WHO.
PROPOSED DIAGNOSIS
Acute myeloid leukemia with normal karyotype and mutated CEBPA
CONSENSUS DIAGNOSIS
Acute myeloid leukemia with heterozygous CEBPA mutation