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Year : 2016  |  Volume : 59  |  Issue : 1  |  Page : 104-106
Acute monoblastic leukemia with abnormal eosinophils and inversion (16): A rare entity

1 Department of Pathology, Christian Medical College, Vellore, Tamil Nadu, India
2 Department of Transfusion Medicine and Immunohematology, Christian Medical College, Vellore, Tamil Nadu, India
3 Department of Haematology, Christian Medical College, Vellore, Tamil Nadu, India
4 Department of Cytogenetics, Christian Medical College, Vellore, Tamil Nadu, India

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Date of Web Publication9-Mar-2016


Acute myeloid leukemia (AML) is a malignant hematopoietic stem cell disorder which is sub-classified based on bone marrow morphology and the presence of specific genetic abnormalities. One such cytogenetic abnormality is the pericentric inversion (inv) of chromosome 16 which is typically seen in AML M4 with eosinophilia and is associated with a favorable prognosis. We report the inv (16) in a young woman with AML M5 and abnormal eosinophils. This is a rare entity with only about 20 cases being reported till date.

Keywords: Acute myeloid leukemia, AML-M5, Eosinophilia, Inversion 16

How to cite this article:
Gnanasekaran KK, Chacko MP, Manipadam MT, Bindra M S, George B, Srivastava VM. Acute monoblastic leukemia with abnormal eosinophils and inversion (16): A rare entity. Indian J Pathol Microbiol 2016;59:104-6

How to cite this URL:
Gnanasekaran KK, Chacko MP, Manipadam MT, Bindra M S, George B, Srivastava VM. Acute monoblastic leukemia with abnormal eosinophils and inversion (16): A rare entity. Indian J Pathol Microbiol [serial online] 2016 [cited 2020 Dec 6];59:104-6. Available from: https://www.ijpmonline.org/text.asp?2016/59/1/104/174829

   Introduction Top

Acute myeloid leukemia (AML) is classified into various subtypes based on lineage differentiation and level of maturation of myeloid cells, as well as the presence of specific genetic abnormalities. One such entity is AML with the inversion (16)(p13.1q22) or t(16;16)(p13.1;q22) which is typically associated with acute myelomonocytic leukemia with abnormal eosinophils (AML-M4Eo). [1] It also may be seen in other subtypes of AML, notably AML M5. [2] AML with inv (16) is associated with a favorable prognosis. A high index of suspicion is required for the identification of inv (16) which may be overlooked because it is a subtle abnormality. We report a de novo AML M5 with abnormal eosinophils and inv (16).

   Case Report Top

A 30-year-old female presented with a two-week history of fever, cough with dyspnea and chest pain, generalized weakness, and erythematous papules over the dorsum of her right hand and bleeding per vaginum.

She had bicytopenia (Hb: 8.6 g/dl, platelet count: 19 10 3 /μL) and leukocytosis (white blood cell count: 294 10 3 /μL) with a differential count of 25% blasts, 55% monocytoid cells, 2% myelocytes, 8% neutrophils, 6% lymphocytes, 3% eosinophils, and 1% basophils. Bone marrow (BM) smears showed solidly cellular fragments and hypercellular cell trails with 81% monoblasts and promonocytes, 8% eosinophils, 8% other myeloid cells, and 3% erythroids. The eosinophils showed large, coarse, and basophilic intracytoplasmic granules [Figure 1]a. Sudan black B positivity was seen in ≥3% of the blasts. With dual esterase stain, 22% of cells showed positivity for nonspecific esterase, 5% showed positivity for chloroacetate esterase, and 73% were neutral [Figure 1]b. The blasts were periodic acid-Schiff negative. Although abnormal eosinophils are typically associated with AML M4, the morphological and cytochemical findings favored a diagnosis of AML M5. Trephine biopsy showed a hypercellular marrow with dense interstitial infiltrates of immature cells and a mild increase in eosinophil precursors [Figure 1]c and d. Skin biopsy was consistent with leukemia cutis with a superficial dermal infiltrate of large cells with moderately pleomorphic round vesicular nuclei, prominent nucleoli, and scant cytoplasm, some of which were positive for myeloperoxidase and CD117 [Figure 2]a and b. Flow cytometry showed expression of CD13, CD33, CD34, CD14, human leukocyte antigen-DR, CD117, and the monocytoid markers CD64 and CD11. Cytogenetic analysis of the BM showed the inv(16)(p13.1q22) [Figure 2]c. The patient was treated with cytarabine and daunorubicin. However, she developed sepsis and succumbed on day 14.
Figure 1: (a) Bone marrow smear, MGG, ×1000: Monoblasts, promonocytes, and abnormal eosinophils. (b) Bone marrow smear, double esterase stain, ×1000: Monocytoid cells, brown; myeloid cells, blue. (c) Trephine biopsy, H&E, ×200: Hypercellular marrow. (d) Trephine biopsy, H&E, ×400: Eosinophilia

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Figure 2: (a) Leukemia cutis, H&E, ×100: Superficial dermal infiltrate of atypical cells. (b) Leukemia cutis, IHC: MPO stain, ×200: Granular cytoplasmic staining. (c) 46XX, inv(16)(p13.1q22)

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   Discussion Top

Among the various morphological subtypes of AML described by the World Health Organization (WHO), AML M4 and AML M5 are associated with monocytic differentiation. The differentiation between these two subtypes is based on the number of monocytoid cells (≤80% in AML M4 and ≥80% AML M5). In AML M4, the myeloid precursors account for at least 20% of the marrow population. [3] Esterase stains are useful in this regard. Nonspecific esterase identifies monocytoid cells, while specific esterase highlights myeloid cells.

AML M5 is commonly associated with bleeding manifestations as well as widespread infiltration of tissues such as the gums, skin, and central nervous system. There are two subtypes of AML M5:AML M5a (monoblastic) with ≥80% monoblasts and AML M5b (monocytic) with ≤80% monoblasts. [3]

Monoblasts are large cells up to 30 μ in diameter with round to oval nuclei, delicate or lace-like chromatin, prominent nucleoli and basophilic cytoplasm. Promonocytes, the next cells in the hierarchy, which are also counted along with the monoblasts, are similar to monoblasts except that their nuclei are convoluted or indented. Monocytes are slightly smaller (up to 25 μ) and have folded nuclei, reticular chromatin, inconspicuous nucleoli, and gray vacuolated cytoplasm. [4]

The pericentric inversion (16) accounts for ~5% of the cytogenetic abnormalities seen in AML and is associated with a favorable prognosis. This abnormality can occur at any age, with a median age of 35 years. The genes involved in this rearrangement are the core binding factor beta (CBFβ) gene at band q22 on the long arm of chromosome 16 and the myosin heavy chain 11 gene (MYH11) at band p13.1 on its short arm. As a result of the inversion, these genes are juxtaposed to form the CBFβ/MYH11 fusion gene which is leukemogenic. Approximately 90% of inv(16) are associated with AML-M4Eo with other morphological subtypes accounting for the remainder. [5] The inv (16) has been reported in only 20 patients with AML M5 till date. [2] The inv (16) was the sole abnormality in 11 patients while nine had one or more additional abnormalities [Table 1].
Table 1: Cases of monocytic leukemia with inv(16)

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According to the WHO classification, if the inv(16) is present, a diagnosis of AML must be made irrespective of the percentage of blasts in the blood or BM. [1] The marrow in AML with inv (16) shows increased numbers of eosinophils at all stages of maturation with abnormal eosinophil precursors being seen in about 85% of cases. These abnormal eosinophilic myelocytes and promyelocytes have large, prominent, dark, almost basophilic granules which may be numerous, obscuring nuclear details. Often, these granules are admixed with the typical eosinophil granules. Other cytological abnormalities such as nuclear hyper/hypolobation and Charcot-Leyden crystals in the mature eosinophils have also been described. [5]

The inv(16) is a subtle abnormality which is difficult to detect by conventional cytogenetics if the morphology of the metaphases is suboptimal; in such instances, fluorescence in situ hybridization using a probe for the CBFβ gene might be necessary for its identification. It is important to note that the presence of abnormal eosinophils in the BM warrants a careful search for this abnormality regardless of the morphological subtype of AML. Identification of this cytogenetic abnormality is important because of its favorable prognosis and a high rate of complete remission when treated with cytarabine.

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Conflicts of interest

There are no conflicts of interest.

   References Top

Vardiman JW, Thiele J, Arber DA, Brunning RD, Borowitz MJ, Porwit A, et al. The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: Rationale and important changes. Blood 2009;114:937-51.  Back to cited text no. 1
Mitelman Database of Chromosome Aberrations and Gene Fusions in Cancer (2015). Mitelman F, Johansson B, Mertens F (Eds.), http://cgap.nci.nih.gov/Chromosomes/Mitelman. [Last accessed on 2015 Feb 01].  Back to cited text no. 2
Brunning RD, Matutes E, Flandrin D, Vardiman J, Bennett J, Head D. Acute myeloid leukaemia not otherwise categorised. In: Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, et al., editors. Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissues. 4 th ed. Lyon: IARC Press; 2008.  Back to cited text no. 3
Goasguen JE, Bennett JM, Bain BJ, Vallespi T, Brunning R, Mufti GJ; International Working Group on Morphology of Myelodysplastic Syndrome. Morphological evaluation of monocytes and their precursors. Haematologica 2009;94:994-7.  Back to cited text no. 4
Bain BJ, Clark DM, Wilkins BS, editors; Acute myeloid leukaemia, Mixed phenotype acute leukaemia, the myelodysplastic syndromes and histiocytic neoplasms. Bone Marrow Pathology. 4 th ed. Hong Kong: Wiley-Blackwell; 2010.  Back to cited text no. 5

Correspondence Address:
Mary P Chacko
Department of Transfusion Medicine and Immunohematology, Christian Medical College, Vellore, Tamil Nadu
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0377-4929.174829

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  [Figure 1], [Figure 2]

  [Table 1]


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