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Micromegakaryocytes (MMGKs), a common finding in bone marrow, have been rarely described in peripheral blood (PB). MMGKs are known to occur commonly in PB of patients diagnosed with Chronic Myeloid Leukemia (CML).1 A characteristic of chronic phase of CML, they are considered to be dysplastic, although they produce morphologically normal platelets. Circulating MMGKs (ie, MMGK in PB) have also been reported in more aggressive types of myelodysplasia (such as refractory anaemia with excess blasts (RAEBs) and refractory anaemia with excess blasts in transformation (RAEB-t) and have been known to correspond to a poor prognosis.2 Circulating MMGKs are also known to occur in cases of hypoplastic myelodysplasia (MDS).3 We highlight a case of acute myeloid leukaemia(AML) demonstrating many MMGKs in PB.
A 25-year-old man presented with chief complaints of left mandibular region swelling for 1 month and gum bleeding with fever for 2 weeks. On examination, the patient had gum hypertrophy, 2 cm palpable liver and cervical lymphadenopathy. His laboratory tests at presentation showed haemoglobin (Hb) level of 61g/L, a Total leucocyte count (TLC) of 10.47×10 3/L and a platelet count of 19 ×109/L. Other laboratory parameters were within normal limits. PB examination showed 86% blasts with many circulating MMGKs (figure 1A). Flow cytometric immunophenotyping(FCMI) of PB showed 62% CD45 dim+blasts which were cMPO+, CD13+, CD34+, CD117+, CD38+ and negative for CD79a, CD7, cCD3, sCD3, CD16, CD123, CD11b, CD36, CD56, CD64, CD4, CD14, CD22 and CD20. Flow cytometry immunophenotyping (FCMI) also identified a cCD41 and cCD61 bright positive population representing MMGK (figure 1B). Bone marrow aspirate showed near total replacement by blasts and occasional megakaryocyte showed dysplastic changes.
BCR-ABL 1 was negative while cytogenetics showed translocation t (6;11) (q27;23). The translocation breakpoint involves the MLL gene, which is the human homologue of the Drosophila trithorax gene, at 11q23 and the AF6 gene at 6q27. The patient was diagnosed as Acute Myeloid Leukemia (AML) M 1 (according to French–American–British classification) and AML not otherwise specified according to the WHO classification. Our patient has been given 3+7 induction of cytarabine and is on follow-up.
Thorough search of literature revealed that the first case of circulating MMGK associated with a leukaemia was reported in 1984 in a 26-year-old man diagnosed with erythroleukaemia.4 Megakaryocytic features were defined by morphological and cytochemical studies using light and electron microscopy with platelet-megakaryocyte peroxidase staining. In another study to gain perspective on platelet production in the fetus and the newborn, large numbers of megakaryocytes, mostly mature, were found in umbilical arteries and veins, more than previously observed circulating in adult blood.5
Circulating MMGKs may be often missed by a naïve screener as they are not only rare but also often lack specific morphological features and may resemble small lymphocytes. These maybe missed on routine Romanowsky stains and some studies3 detected these immunocytochemically with monoclonal antibodies to platelet glycoprotein Ila. As many as 34 % of MDS cases demonstrated MMGK in peripheral blood.2 Elghetany et al’s study sharply contrasted with observations of FAB group6 which stated that ‘rarely micromegakaryocytes can be seen in peripheral blood’. MMGKs were also found to be more common in RAEB-1 and RAEB-2 which are known to possess dysmegakaryocytic features in bone marrow. The study also postulated that the presence of these circulating MMGKs may predict their evolution into acute leukaemia and hence a routine evaluation of PB films for these cells could be warranted in the future as a part of clinical workup. In some cases of acute myeloid leukaemia, Immuno-alkaline phosphatase staining(APAAP) staining of blood smears revealed circulating pro-megakaryoblasts and MMGKs.7
This is an interesting and first case of circulating micromegakaryocytes associated with AML.
It highlights the importance of morphological evaluation of peripheral blood.
Its association with impact on prognosis or treatment outcome, if any, needs to be evaluated by observing such cells in other smears of AML.
GJ and CK are joint first authors.
Contributors CK, GJ and AC screened the morphology slides and reported the flow cytometry. CK and GJ wrote the manuscript and AC approved the same with suggestions and guidance.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Disclaimer Case reports provide a valuable learning resource for the scientific community and can indicate areas of interest for future research. They should not be used in isolation to guide treatment choices or public health policy.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.
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