PMC5614759_01
Patient 1: (A): Bone marrow biopsy from 2013 shows granulocytic hyperplasia. Megakaryocytes are increased in numbers with frequent clusters, including occasional hyperchromatic forms. (B): Reticulin stain on 2013 bone marrow biopsy shows marked fibrosis. (C): Bone marrow biopsy from 2015 shows sheets of myeloid blasts, consistent with acute myeloid leukemia. (D): Molecular analysis shows CALR mutant allele frequency increased over time, with appearance of IDH2 mutation and transient BCR-ABL1 positivity.
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Her first bone marrow biopsy in 2013 showed a hypercellular marrow, with granulocytic hyperplasia, increased megakaryocytes with hyperchromatic forms and marked reticulin fibrosis (Fig. 1A,B). The bone marrow demonstrated acute myeloid leukemia in a background of extensive fibrosis (Fig. 1C). Examination of the mutant allele frequencies over time suggests that the CALR was the earliest genetic event and the founder mutation of patient's MPN (Fig. 1D).
PMC5614759_02
Patient 2: (A): Rare dysplastic neutrophils are noted in the peripheral blood smear. (B): Bone marrow aspirate smear shows occasional dysplastic megakaryocytes with nuclear separation.
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However, occasional dysplastic megakaryocytes with nuclear separation that are often present in myelodysplastic syndromes (MDS) were also seen (Fig. 2).