Case 337

Submitting Author: McClure, Rebecca Frances, MD
Institution: Mayo Clinic
Additional authors:Rhett P. Ketterling MD
Session: AML with myelodysplasia-related changes

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HISTORY

59 yo female, 8 yr Hx non-insulin dependent diabetes mellitus Medications: Actos (oral thiazolidinedione), BYETTA (injectable blood sugar control), Lisinopril (ACE-inhibitor) 6/2012 – “losing stamina while dancing” Hb 7.2 g/dL WBC 1.6 x109/L Plt 100 x109/L Bone marrow: “fairly normal”, MPN-like megakaryocytes Flow: normal Karyotype: normal MDS FISH: normal Dx: Chronic myeloid neoplasm, NOS 8/2012 Hb 7.4 g/dL WBC 1.7 x109/L Plt 95 x109/L Blood: Circulating neutrophil and RBC precursors BM: 60% cellular, increased neutrophils, increased megakaryocytes (MPN-like), gr1 reticulin, no increase in blasts Flow: normal Karyotype: 46,XX,inv(3)(p21q27)[3]/46,XX[17] FISH: RPN1/MECOM in 7% nuclei (MECOM=EVI1) JAK2 V617F: negative MPL exon 10: negative Dx: Chronic myeloid neoplasm, NOS

DETAILS

11/2012 - Specimen for case presentation Hb 8.6 g/dL WBC 1.7 x109/L Plt 122 x109/L Blood: circulating neutrophil and RBC precursors, 15% circulating blasts BM aspirate: sparsely cellular, 18-21% blasts on Bx touch prep, ring sideroblasts BM Bx: 60% cellular, increased megakaryocytes (MPN/MDS-like & ? megakaryoblasts), decreased RBC precursors, intrasinusoidal hematopoiesis, gr1 reticulin fibrosis

IMMUNOHISTOCHEMISTRY AND FLOW CYTOMETRY

Immunoperoxidase stains: CD61 marked increase, CD34 borderline increase , CD117 moderate increase

Flow: Blasts 15% - express CD13, CD34, CD117, HLA-DR, CD45(dim), CD5(dim), CD7(dim)

CYTOGENETIC FINDINGS

Karyotype: 46,XX,der(3)inv(3)(p21q27)inv(3)(p21q26.2)[16]/46,XX[4] complex rearrangement of chromosome 3 in 16 metaphases FISH: RPN1/MECOM in 36% nuclei (MECOM=EVI1)

MOLECULAR FINDINGS

INTERESTING FEATURES

Tracked progression of evolving inv(3) from relatively normal to AML
Classification dilemma when have inv(3) with increased blast <20%
Nicely demonstrates mixed myeloproliferative/myelodysplastic features frequently seen with this genetic abnormality
Unusual inv(3) abnormality

PROPOSED DIAGNOSIS

Acute myelogenous leukemia with inv(3)(q21q26.2);RPN1-EVI1 arising from a prior chronic mixed myeloproliferative/myelodysplastic neoplasm, NOS (favored) or mixed myeloproliferative/myelodysplastic neoplasm, unclassifiable with increased blasts

CONSENSUS DIAGNOSIS

Acute myelogenous leukemia with myelodysplasia-related changes, with inv(3)(q21q26.2);RPN1-EVI1, arising from myeloproliferative/myelodysplastic neoplasm