Myeloproliferative Neoplasm or Reactive Process? A Rare Case of Acute Myeloid Leukemia and Transient Post-Treatment Megakaryocytic Hyperplasia with JAK-2 Mutation

Extract

Administration of granulocyte-macrophage colony-stimulating factor (GM-CSF) to patients who had received chemotherapy for acute myeloid leukemia (AML) has been found to cause a transient increase in the number of marrow megakaryocytes with no subsequent increase in the peripheral platelet count. Here we report a 33-year-old male patient who was diagnosed with a de novo AML-M1 with no known history of chronic myeloproliferative disease. His first marrow biopsy on 9/6/2013 showed 95% cellularity with 70% CD13, CD33, CD117, HLA-DR(+), CD34(−) myeloblasts demonstrating Sudan black B positivity. Cytogenetic study revealed a normal karyotype with NPM-1 mutation. The patient achieved complete remission after induction therapy with FLAG-Ida. GM-CSF was given following induction and a cycle of HiDAC consolidation started in 11/2013. The postinduction marrow showed granulocytic hyperplasia, marked increased megakaryocytes (25/HPF), reticulin fibrosis (3/4), and a peripheral platelet count of 731,000/uL. No residual acute leukemia was identified. Based on the findings, JAK2 mutation analysis was performed and a JAK-2 V617F mutation was detected. The subsequent marrow biopsy in 3/2014 revealed a normocellular marrow with mild megakaryocytic hyperplasia (7/HPF), a peripheral platelet count of 358,000/uL and complete resolution of marrow fibrosis. The JAK-2 mutation remains positive. The findings of resolving megakaryocytic hyperplasia and reticulin fibrosis with normalization of the platelet count are suggestive of a reactive process. However, the presence of the JAK2 mutation indicates a pre-existing chronic myeloproliferative disorder. It is also possible that the patient's AML may have arisen from a previously undiagnosed chronic myeloproliferative disorder, two separate and distinct stem cell disorders, or less likely a de novo AML with JAK2 mutation. This rare case demonstrates the challenges of firmly establishing a diagnosis between similar, but distinct, disease entities. Further clinical follow-up, synthesized interpretation of available data and review of the literature are required to reach the correct diagnosis.