Indian Journal of Pathology and Microbiology

LETTER TO EDITOR
Year
: 2014  |  Volume : 57  |  Issue : 3  |  Page : 512--514

Acute megakaryoblastic leukemia M7 presenting with extreme myelofibrosis


Aniket Kumbhojkar, Rajesh Kulkarni, Akash Chheda, Prakash Gambhir, Aarti Kinikar, Sandhya Khadse 
 Department of Pediatrics, B J Government Medical College, Pune, Maharashtra, India

Correspondence Address:
Rajesh Kulkarni
B J Government Medical College, Pune, Maharashtra
India




How to cite this article:
Kumbhojkar A, Kulkarni R, Chheda A, Gambhir P, Kinikar A, Khadse S. Acute megakaryoblastic leukemia M7 presenting with extreme myelofibrosis.Indian J Pathol Microbiol 2014;57:512-514


How to cite this URL:
Kumbhojkar A, Kulkarni R, Chheda A, Gambhir P, Kinikar A, Khadse S. Acute megakaryoblastic leukemia M7 presenting with extreme myelofibrosis. Indian J Pathol Microbiol [serial online] 2014 [cited 2022 Dec 6 ];57:512-514
Available from: https://www.ijpmonline.org/text.asp?2014/57/3/512/138812


Full Text

Editor,

AMKL is a rare type of leukemia in children.Myelofibrosis in AMKL is known but is rare. Myelofibrosis may result in a 'dry tap' leading to difficulty in diagnosis on bone marrow aspiration.Bone marrow biopsy with immunophenotyping clinches the diagnosis in such cases.

A 6-month-old baby boy third child of nonconsanguineous marriage was referred to our hospital for progressive pallor and excessive crying since 1-month and fever since 15 days. There was no history of bleeding from any site or jaundice. Patient had received blood transfusion in the past at the age of 3 and 5 months without any investigations. Child was 2.2 kg at birth with normal development. There was history of death of one sibling at the age of 11 months due to severe anemia and abdominal distension, evaluation was not done in that child. There was no history of transfusion dependent anemia in the family.

On examination, child was severely pale with tachypnea and tachycardia. There was no evidence of lymphadenopathy, icterus or bleeding from any site. There were no dysmorphic features. Child had moderate acute malnutrition. Systemic examination revealed hepatosplenomegaly (liver 9 cm, spleen 4 cm firm nontender). Rest of the examination was normal.

Hemogram revealed severe anemia (Hb 2.7 g%), thrombocytopenia (platelet count 48,000) with white blood cell count of 7900 (77% lymphocytes, 14% neutrophils, 4% monocytes, 1% basophils and 4% blasts). Peripheral blood smear examination showed normocytic normochromic and occasional Nucletaed RBCS. Neutropenia with blasts seen as 10-12 micron in size with scanty blue cytoplasm and indistinct nucleolus. Platelets diminished in number.

Bone marrow aspiration returned dry tap. Bone marrow biopsy done showed normal bony trabeculae with fibrotic marrow spaces with normal hematopoisis suppressed. Grade III to IV fibrosis [Figure 1] and [Figure 2] with only few foci of hematopoietic cells were seen. Few round cells with scanty cytoplasm of inconspicuous morphology suggestive of blasts were present. Few such cells showed hemophagocytosis. Erythroid and megakaryocytic series were markedly diminished. Impression was myelofibrosis secondary to infiltration.{Figure 1}{Figure 2}

Bone marrow biopsy immunophenotyping was done showed immature cells that are squeezed in fibrous stroma. These cells strongly expressed CD34, C-kit and dimly expressed CD43, CD4and CD61 suggesting myeloid blasts expressing megakaryocytic phenotype. Myeloperoxidase was not expressed. CD68, CD123, CD7, and CD3 were not expressed. Impression was acute myeloid leukemia of megakaryocytic type with extreme myelofibrosis.

Cytogenetic study was planned to define underlying mutation, but was not done due to financial constraints. Parents were explained regarding nature of disease and its prognosis. They gave negative consent for chemotherapy. Patient is following up with us for palliative blood transfusion as and when required.

Acute megakaryoblastic leukemia (AMKL) is a very rare type of leukemia with poor prognosis. It represents approximately 3.1-10% of all childhood leukemia's with incidence of 0.5/million/year. [1] Patients with Down syndrome (DS) have increased incidence of AMKL however prognosis of AMKL in DS is better than general population. [3] AMKL may present in variety of ways. Nonspecific symptoms may be irritability, weakness, and dizziness. Specific symptoms are due to various cell line involvement viz. pallor, fever, mucocutaneous bleeding. Hepatosplenomegaly is a common finding, but lymphadenopathy is uncommon. [4] Neurological manifestations are headache, projectile vomiting, papilledema, cranial nerve palsies, chloromas due infiltration of tumor cells. Our patient presented with severe anemia, thrombocytopenia, and hepatosplenomegaly.

There are three types of AMKL. It can arise de novo, postchemotherapy or can progress from myeloproliferative syndrome. [2] Our patient had de novo AMKL without any phenotypic features of DS.

Bone marrow biopsy is essential because bone marrow aspiration is inconclusive frequently. In our patient bone marrow aspiration failed requiring bone marrow biopsy for confirmatory diagnosis. Hemophagocytosis and extreme myelofibrosis are commonly associated with AMKL. [5] Immunophenotyping is very rewarding in confirming diagnosis because AMKL is among very few types of acute megakaryoblastic leukaemia (AML) that unequivocally be proved by immunophenotyping. [6] CD34 and C kit positivity are markers of myeloid type of leukemia but are not specific for any particular subtype of AML. [7] CD61 positivity is specific marker for megakaryocytic type of leukemia. [3] Blasts in DS have aberrant expression of T cell marker CD7 unlike rest of AML. [8] In our patient, CD34, C-kit and CD61 markers were positive and CD7 was negative.

According to Children oncology group guidelines chemotherapy is with two cycles of induction therapy with infusions of daunomycin, cytosine arabinoside, etoposide (ADE therapy). After remission is induced, postinduction treatment is necessary, because more than 90% of patients otherwise relapse without additional treatment. [9] In patients without human leukocyte antigen-matched donors from their family, sequential cycles of chemotherapy are administered by using combinations of cytosine arabinoside and etoposide, mitoxantrone and cytosine arabinoside, and finally, high-dose cytosine arabinoside with L-asparaginase. Allogeneic bone marrow transplantation has been shown to reduce relapse rates but does not always improve overall survival because of treatment-related mortality. Chemotherapy in patients with DS is with reduced intensity and bone marrow transplantation is reserved for the second remission after a relapse. [9]

Advances in molecular pathology in recent years have helped us understanding biology of AML and development of treatment options however cure rates of AML have increased modestly in past decades. [10] Complex chromosomal aberrations predict poor outcome in spite of intensive chemotherapy. Children's cancer group investigators recently reported that the estimated rate of 4-year disease-free survival in this group of children was only 21%. [3] Cytogenetic factors are important in prognostication of AMKL; however, CD34 positivity is independent unfavorable prognostic factor in newly diagnosed AMKL patients. [11]

In our case, AMKL was de novo without associated DS, progression of disease was not fulminant, also in this case one sibling was having severe pallor and abdominal distension who died undiagnosed with possibility of similar illness in that child.

Recent WHO classification is based on cytogenetic studies but these are not readily available in our country. Clinical course, bone marrow biopsy and immunophenotyping can be diagnostic of few forms of leukemia like AMKL.

References

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