Acute megakaryoblastic myeloid leukemia is a subtype of Acute Myeloid Leukemia (AML), defined by the presence of at least 20% blasts in the bone marrow, half of which belongs to the megakaryocytic lineage. The observation of more or less clearly differentiated micro megakaryocytes is often described [1]. We report the case of AML7 in a child diagnosed in our hematology laboratory. 

Observation

This is a 2-year-old Moroccan child, presented with a complete medullary insufficiency syndrome made up of generalized mucocutaneous pallor, bruises and bone pain, especially femoral, all of which progressed in a context of fever and deterioration of general condition. A blood count has been requested. it showed a bicytopenia: normochromic, normocytic aregenerative anemia (Hb = 6.2 G/dl; VGM = 78.8 fl; TCMH = 24.3 and reticulocyte count = 65000/μl), Thrombocytopenia (Platelets = 130 G/L) and hyperleukocytosis (GB = 13.79 G/L). This CBC was completed by a blood smear which objectified the presence of 50% of megakaryoblasts (Figure 1a) and small cells with round nucleus with condensed chromatin and mature cytoplasm of general texture of platelet orienting towards the micromegacryocytes (Figure 1b). 

Figure 1: Megakaryoblast from Blood Smear

A myelogram was carried out, the report of which detailed the presence of 93% of blasts of heterogeneous size, with a bilobed nucleus and loose chromatin. The cytoplasm is agranular hyperbasophilic. Some blasts have outer buds or pseudopodia orienting towards megakaryoblasts (Figure 2). The MPO was negative. As part of a multidisciplinary approach with cytology and in order to confirm the diagnosis of AML 7, immunophenotyping was performed. It showed weak CD45+blasts partially expressing the CD34 immaturity marker. CD33 and CD117 are positive.

Platelet markers, in particular CD 41 and CD 61, are positive. The B and T lymphoid markers are negative. Aberrant expression of CD56 was noted. The cytogenetic study was normal. The diagnosis of AMegL was retained. The patient initially received induction chemotherapy with favorable evolution.

Figure 2: Megakaryoblasts in Bone Marrow Smear

Acute megakaryoblastic leukemia (AMegL) is a hematological neoplasm characterized by clonal proliferation of primitive megakaryocytes. In the most recent 2016 WHO revision of myeloid neoplasms, AMegL is included in Acute Myeloid Leukemia Not Otherwise Specified (AML NOS) [1] and defined as ≥20% blasts in bone marrow cellularity, of which ≥50% are of the megakaryocyte lineage [2].

In pediatric population, the disease is divided into two major subgroups: AMegL in individuals with constitutional Down syndrome (DS-AMegL), which has a 150- fold greater incidence compared to the general pediatric population and has a positive prognosis. The second subgroup is de novo AMegL without Down syndrome (not DS-AMegL), which is usually associated with a poor prognosis and accounts for roughly 4-15 percent of all pediatric acute myeloid leukemia cases [3]. 

The diagnosis based primarily on complete blood count, which in the vast majority of cases shows cytopenia, especially thrombocytopenia or even pancytopenia [4].

The blood smear may reveal the presence of myeloid blasts in which the presence of micromegakarblasts. The Specific megakaryocytic origin is defined first by cytology (large cells with abundant cytoplasm, high nuclear to cytoplasm ratio and up to three distinct nucleoli) and then confirmed by flow cytometry [1].

Bone marrow aspiration is often challenging, due to extensive fibrosis induced by megacaryocytes, a condition commonly known as dry tap. reveals extensive myelofibrosis, which often makes aspiration in these patients difficult, In these cases, bone marrow biopsy, followed by immunohistochemistry is performed [1].

The threshold of 20% of blasts, more than half of which are megakaryoblasts, of unequal size, irregular nucleus loose and nucleolated chromatin, agranular basophilic cytoplasm often containing peripheral budding and sometimes containing platelets in the marrow, allows the diagnosis of acute megakaryoblastic leukemia. The cytochemistry and especially the reaction to myeloperoxidase is not very useful in AMegL because it is generally negative [4]. Nevertheless, the study of the expression of specific surface markers of platelets by immunophenotyping remains essential, because it makes it possible to establish the diagnosis with certainty by the expression of platelet antigens gp IIb/IIIa (CD41), gp IIIa (CD61) and gp Ib (CD42) on the surface of blasts [5].

AMegL is a separate entity that requires special attention from the cytologist. Immunophenotyping is the cornerstone of the diagnosis and the presence of cytogenetic abnormalities determines the prognosis.

1. De Marchi, F. et al. “Molecular Features, Prognosis, and Novel Treatment Options for Pediatric Acute Megakaryoblastic Leukemia.” Expert Review of Hematology, vol. 12, no. 5, 2019, pp. 285-293. https://doi.org/10.1080/ 17474086.2019.1609351.

2. Swerdlow, S.H. et al. “The 2016 Revision of the World Health Organization Classification of Lymphoid Neoplasms.” Blood, vol. 127, no. 20, 2016, pp. 2375-2390. https://doi.org/10. 1182/blood-2016-01-643569.

3. Pagano, L. et al. “Acute Megakaryoblastic Leukemia: Experience of GIMEMA Trials.” Leukemia, vol. 16, no. 9, 2002, pp. 1622-1626. https://doi.org/10.1038/sj.leu.240 2618.

4. Athale, U.H. et al. “Biology and Outcome of Childhood Acute Megakaryoblastic Leukemia: A Single Institution’s Experience.” Blood, vol. 97, no. 12, 2001, pp. 3727-3732. https://doi.org/10.1182/blood.v97.12.3727.

5. Lopez, C.K. et al. “Pediatric Acute Megakaryoblastic Leukemia: Multitasking Fusion Proteins and Oncogenic Cooperations.” Trends in Cancer, vol. 3, no. 9, 2017, pp. 631-642. https://doi.org/10.1016/j.trecan.2017.07.003.