Institution: University of Pittsburgh
Additional authors:Eric Safyan, MD
Session: AML with recurrent genetic abnormalities Part I
HISTORY
35 year old male who presented with ecchymosis, cough, and subconjunctival hemorrhages. There is no history of prior malignancy or splenomegaly. Peripheral blood evaluation showed leukocytosis (59.6 x10^9/L), anemia (Hg 8 g/dL) and thrombocytopenia (17 x 10^9/L) as well as 44% circulating blasts (see peripheral blood smear image)
DETAILS
Wright-Giemsa-stained bone marrow aspirate smears showed 48% blasts and increased (11%) eosinophils and their precursors (see image). Subset of the blasts/immature cells show prominent dense purple-violet granules (see image). Cytochemical stains showed that the blasts were positive for for MPO and NSE. No bone marrow biopsy was received.
IMMUNOHISTOCHEMISTRY AND FLOW CYTOMETRY
Flow cytometric studies showed the following myeloid blast phenotype: dim CD45 positive, CD34 positive, CD117 positive, HLA-DR positive, CD14 negative, CD36 negative, CD64 subset positive, CD7 negative, CD56 positive, MPO negative, TdT negative, CD3 negative (surface and cytoplasmic)
CYTOGENETIC FINDINGS
Classical cytogenetic studies show the following karyotype: 46,XY,der(16)inv(16)(p13q22)del(16)(p11.2p13.1)[2]/46,XY,idem,t(9;22)(q34;q11.2)[18]
Fluorescence in situ hybridization studies are positive for the BCR/ABL1 and CBFB gene rearrangements, and is negative for the PML/RARA gene rearrangement.MOLECULAR FINDINGS
Quantitative real-time PCR analysis for the BCR/ABL fusion transcript is positive at the BCR/ABL minor breakpoint region, and negative at the BCR/ABL major breakpoint region.
INTERESTING FEATURES
The coexistence of t(9;22) and inversion 16 is uncommon, and usually occurs in the clinical context of blast-phase chronic myelogenous leukemia and portends a poor prognosis. However, in de novo AML, acquisition of t(9;22) does not appear to impact the favorable prognosis when inversion (16) is the primary event. These cases are also characterized by involvement by the minor BCR/ABL breakpoint (p190 fusion transcript). Clinical-pathologic correlation is essential in establishing the diagnosis. In our case, the patient received induction and consolidation chemotherapy as well as daily imatinib and has remained in complete remission over 3 years.
PROPOSED DIAGNOSIS
De novo acute myeloid leukemia with inversion (16)(CBFB-MYH11) and t(9;22)/BCR/ABL.
CONSENSUS DIAGNOSIS
Acute myeloid leukemia with inv(16)(p13.1q22); CBFB-MYH11, and t(9;22)(q34;q11.2); BCR-ABL1 as possible clonal evolution