Case 333

Submitting Author: McClure, Rebecca Frances, MD
Institution: Mayo Clinic
Additional authors:Rhett P. Ketterling MD
Session: Therapy-related myeloid neoplasms

HISTORY

46 yo male 25 pack-year Hx smoking, quit 5 yrs prior to initial symptoms Aspestos exposure 4/2004 – Shortness of breath, 20lb weight loss, lung nodules Dx: Large B-cell lymphoma associated with EBV (WHO- lymphomatoid granulomatosis, grade 1) Rx: CHOP + rituximab for 2 cycles R-EPOCH x 3 cycles cyclophosphamide 3/2005 - Blood and bone marrow specimens presented in this case

DETAILS

Blood: Hb: 12.4 g/dL WBC 9.8 x109/L 13% blasts, monocytosis Plt 109 x109/L Bone Marrow: 90% cellular 40% blasts/promonocytes with atypical eosinophilic granules, 10% monocytes, 21% eosinophil precursors, dysplastic neutrophils

IMMUNOHISTOCHEMISTRY AND FLOW CYTOMETRY

Flow: Blasts expressing CD13,CD33, CD117, CD34 (partial), HLA-DR (partial)

CYTOGENETIC FINDINGS

Karyotype: 46,XY,inv(16)(p13.1q22)[12]/46,XY[8]

FISH: Rearrangement of CBFB in 59% of nuclei

MOLECULAR FINDINGS

Sanger Sequencing: KIT mutations exons 8 & 17 negative

INTERESTING FEATURES

Classification alert for therapy-related myeloid neoplasms that might otherwise fit in WHO category of AML with a recurrent genetic abnormality
Prognostic implications and significance of KIT mutations in this setting can be discussed
Nice example of inv(16) cytology and genetics

PROPOSED DIAGNOSIS

Therapy-related acute myeloid leukemia with inv(16)(p13.1q22);CBFB-MYH11

CONSENSUS DIAGNOSIS

Therapy-related myeloid neoplasm, acute myeloid leukemia with inv(16)(p13.1q22); CBFB-MYH11