Acute myeloid leukemia with inv(16)(p13.1q22), abnormal eosinophils, and absence of peripheral blood and bone marrow blasts

Abstract

Acute myeloid leukemia with inv(16)(p13.1q22), abnormal eosinophils, and absence of peripheral blood and bone marrow blasts To the Editor: Acute myeloid leukemia (AML) with inv(16)(p13.1q22) [inv(16)] or t(16;16)(p13.1;q22) [t(16;16)] is one of the biologically distinct AMLs in the category of AML with recurrent genetic abnormalities that does not account for blast percentage in the 2008 World Health Organization (WHO) classification. AML with inv(16) accounts for 5-8% of AML and it is usually associated with a relatively favorable prognosis with complete remission rates of 87% [1][2][3]. It usually presents as acute myelomonocytic leukemia and increased eosinophils by morphology in the bone marrow (BM) and/or peripheral blood (PB). One of the most distinctive features is the presence of abnormally large, coarse, purple-violet granules in the eosinophils and eosinophilic precursors. Vacuolation or hypersegmentation can be often observed in eosinophils. Monocytic and granulocytic differentiation is present although granulocytes may show dysplastic features such as cytoplasmic hypogranulation and/or abnormal segmentation.Here we describe an extremely rare case of AML with inv(16). A 54-year-old man presented with respiratory failure and hemoptysis. On admission, complete blood cell (CBC) count showed normocytic anemia, thrombocytopenia and mild monocytosis without leukocytosis or left-shift. Since three days after admission, CBC count has showed persistent leukocytosis (up to 38.3 3 10 3 /uL) with absolute monocytosis (up to 31.85 3 10 3 /uL). However, no circulating blasts or eosinophils were noted. Flow cytometric analysis on PB cells demonstrated an abnormal immunophenotype in the monocytic population with aberrant expression of CD2 and CD3 without the coexistence of myeloid blasts. The patient was started on Hydroxyurea (500 mg/daily) for the presumed diagnosis of chronic myelomonocytic leukemia. Subsequent BM biopsy showed hypercellular marrow (70-80%) with trilineage hematopoietic maturation and increased eosinophils (Fig. 1C). A 500-cell differential count on adequate aspirate smears demonstrated 0% blasts, 17% CORRESPONDENCE myelocytes to segmented neutrophils, 9% eosinophils, 5% monocytes, 42% erythroid precursors, 21% lymphocytes, and 6% plasma cells. Interestingly, many mature and immature eosinophils were present with large coarse basophilic granules, abnormal nuclear segmentation, and occasional cytoplasmic vacuoles (Fig. 1D-F). In addition, mild dysgranulopoiesis was noted. A CD34 immunohistochemical stain demonstrated the absence of blasts in the BM biopsy (inlet in Fig. 1C). PDGFRA and PDGFRB translocations were negative by fluorescent in situ hybridization (FISH). BCR/ABL1 fusion transcripts and KIT (exons 8 and 17) mutations were negative by polymerase chain reaction (PCR). Cytogenetic testing showed a 46 XY, inv (16) (Fig. 1A). FISH analysis using break-apart probes in the BM cells confirmed the presence of CBFB/MYH11 translocation in 53 of 200 (27%) interphase nuclei (Fig. 1B). A comprehensive...

Automated Deep Learning-Based Diagnosis and Molecular Characterization of Acute Myeloid Leukemia using Flow Cytometry

“…Finally, some markers show strong importance for individual models but otherwise weak importance. For example, monocytic markers CD14 and CD64 had high importance scores for prediction of inv(16)/t(16;16)( CBFB :: MYH11 ), which often exhibits monocytic differentiation 33 . Additionally, CD117 had a relatively high importance score for prediction of IDH2 mutations; prior studies have associated IDH2 R172 mutations with high CD117 expression 34 , and IDH2 -targeting therapies have been shown to decrease CD117 expression in AML 35 .…”

Review of Peripheral Blood Eosinophilia: Workup and Differential Diagnosis

“…Acute eosinophilic leukemia, an acute myelomonocytic leukemia with eosinophilia or M4Eo, is a specific subcategory of acute myeloid leukemia and is not considered to be a part of the myeloid/lymphoid neoplasms with eosinophilia that was mentioned above. M4Eo shows a distinct translocation on chromosome 16 (inv(16) and t16;16), which leads to the fusion of the CBFB gene to the smooth muscle myosin heavy MYH111, resulting in the CBFB-MYH11 fusion gene [109,110]. This fusion disrupts normal hematopoiesis and bone development, leading to impaired hematopoietic maturation and leukemogenesis [109].…”

“…M4Eo shows a distinct translocation on chromosome 16 (inv(16) and t16;16), which leads to the fusion of the CBFB gene to the smooth muscle myosin heavy MYH111, resulting in the CBFB-MYH11 fusion gene [109,110]. This fusion disrupts normal hematopoiesis and bone development, leading to impaired hematopoietic maturation and leukemogenesis [109]. Clinically, patients with M4EO have symptoms, such as fever and weight loss, that are found with other categories of AML.…”

“…However, this subcategory seems to present with organomegaly and is more common in younger patient populations [111][112][113]. There is a high index for suspicion for M4Eo when the peripheral smear exhibits 5-10% eosinophils with distinct large basophilic granules and the typical eosinophilic granules in bone marrow aspirations [109,110,112]. Further investigation via fluorescent in situ hybridization, PCR, and cytogenetic testing can clarify this diagnosis.…”

The expression of CCL11/eotaxin, CCR3 receptor and eosinophil peroxidase in tumor tissue in gastric and colon cancers

“…(2007), повышение активности ЕРХ в ýозинофилах крови отмечается при множественной миеломе и лимфогранулематозе, ассоциированных с ýозинофилией [13]. Другие исследователи отмечали высокую активность ЕРХ в крови при миелоидном лейкозе [22]. В свою очередь, S. Schroeder et al (2017) идентифицировали увеличение концентрации отдельных белков ýозинофильных гранул у больных с негематологическими опухолями.…”