The bone marrow core biopsies are 0.5 cm and 1.9 cm. The subcortical area is hypocellular; however, the overall cellularity is 40%. There is a proliferation of atypical megakaryocytes that are small and mono-lobated/bi-lobated in a fibrotic background. There are focal clusters of cells that are suspicious for blasts demonstrating convoluted nuclear membranes and small but distinct nucleoli. Immunohistochemical stain with CD34 highlights a population of blasts that vary in size from small to medium and account for ~20% of the marrow cellularity. Background granulopoiesis and erythropoiesis are progressive. There is background stromal damage and edema as well as multifocal lipogranulomas.  A reticulin stain is performed and shows focally mild to moderately increased fibrosis (MF 1-2/3).

The aspirate smears demonstrates blasts that show similar morphologic findings as the peripheral blood smear and the bone marrow core biopsy. There are numerous megakaryocytes that are small in size and are mono-lobated/bi-lobated. Erythroid precursors demonstrate dysplastic features including irregular nuclear membranes, nuclear blebbing, and rare bi-nucleate forms. 

The blasts account for ~20% of live events (CD45 intermediate, SSC intermediate). The blasts are positive for CD34, CD117, CD33, CD13, CD38, HLA-DR, and aberrant CD7 (partial), a frequent finding in this AML. The blasts are negative for CD16, CD19 and CD65. These findings are immunophenotypically consistent with the patient's previous diagnosis.

At the time of diagnosis cytogenetics was positive for a t(3;3)(q21;q26.2) and a loss of chromosome 7. At the time of relapse, three years after diagnosis cytogenetics was positive for a t(3;3)(q21;q26.2) and a loss of chromosome 7 as well as a t(11;21)(p11.2;q22.1). The t(3;3) is a recurring abnormality in AML, and is associated with abnormalities of megakaryocytes in the bone marrow. The loss of chromosome 7 is a recurring abnormality in myeloid neoplasms and is commonly observed in associated with t(3;3). The significance of the t(11;21) observed at the time of relapse is uncertain, but represents clonal evolution.

Fluorescence in situ hybridization (FISH) analysis using a tri-color EVI1 (MECOM) break-apart probe demonstrates one tri-color (red/green/aqua) fusion signal and one green/aqua and separate red signal, indicative of a t(3;3).