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LETTER TO EDITOR  
Year : 2014  |  Volume : 57  |  Issue : 3  |  Page : 512-514
Acute megakaryoblastic leukemia M7 presenting with extreme myelofibrosis


Department of Pediatrics, B J Government Medical College, Pune, Maharashtra, India

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Date of Web Publication14-Aug-2014
 

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;57:512-4

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 2020 Mar 30];57:512-4. Available from: http://www.ijpmonline.org/text.asp?2014/57/3/512/138812


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: Bone marrow biopsy showing myelofibrosis (H and E)

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Figure 2: Bone marrow biopsy reticulin stain

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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 Top

1.
Mandal G, Dewan K, Mondal M, Lath C, Basu R, Bera H. Acute megakaryoblastic leukaemia (AML M7): Rare association of Down syndrome and haemoglobin E-beta thalassaemia. IOSR J Dent Med Sci 2013;5:65-7.  Back to cited text no. 1
    
2.
Sharma S, Nangia A, Jain Malhotra S, Narayan S, Harbhajanka A, Singh S. Clinico-haematological profile of acute megakaryoblastic leukaemia: Report of five cases. Adv Hematol 2009;2009:461912.  Back to cited text no. 2
    
3.
Athale UH, Razzouk BI, Raimondi SC, Tong X, Behm FG, Head DR, et al. Biology and outcome of childhood acute megakaryoblastic leukemia: A single institution's experience. Blood 2001;97:3727-32.  Back to cited text no. 3
    
4.
Bain BJ, Catovsky D, O'Brien M, Prentice HG, Lawlor E, Kumaran TO, et al. Megakaryoblastic leukemia presenting as acute myelofibrosis - A study of four cases with the platelet-peroxidase reaction. Blood 1981;58:206-13.  Back to cited text no. 4
    
5.
Imashuku S, Hibi S, Sako M, Lin YW, Ikuta K, Nakata Y, et al. Hemophagocytosis by leukemic blasts in 7 acute myeloid leukemia cases with t(16;21)(p11;q22): Common morphologic characteristics for this type of leukemia. Cancer 2000;88:1970-5.  Back to cited text no. 5
    
6.
Bene MC, Castoldi G, Knapp W, Ludwig WD, Matutes E, Orfao A, et al. Proposals for the immunological classification of acute leukemias. European Group for the Immunological Characterization of Leukemias (EGIL). Leukemia 1995;9:1783-6.  Back to cited text no. 6
    
7.
Bene MC, Bernier M, Casasnovas RO, Castoldi G, Knapp W, Lanza F, et al. The reliability and specificity of c-kit for the diagnosis of acute myeloid leukemias and undifferentiated leukemias. The European Group for the Immunological Classification of Leukemias (EGIL). Blood 1998;92:596-9.  Back to cited text no. 7
    
8.
Karandikar NJ, Aquino DB, McKenna RW, Kroft SH. Transient myeloproliferative disorder and acute myeloid leukemia in Down syndrome. An immunophenotypic analysis. Am J Clin Pathol 2001;116:204-10.  Back to cited text no. 8
    
9.
Landier W, Wallace WH, Hudson MM. Long-term follow-up of pediatric cancer survivors: education, surveillance, and screening. Pediatric Blood Cancer 2006;46:149-58.  Back to cited text no. 9
    
10.
Ghosh S, Shinde SC, Kumaran GS, Sapre RS, Dhond SR, Badrinath Y, et al. Haematologic and immunophenotypic profile of acute myeloid leukemia: An experience of Tata Memorial Hospital. Indian J Cancer 2003;40:71-76.  Back to cited text no. 10
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11.
Junghanss C, Waak M, Knopp A, Kleine HD, Kundt G, Leithäuser M, et al. Multivariate analyses of prognostic factors in acute myeloid leukemia: Relevance of cytogenetic abnormalities and CD34 expression. Neoplasma 2005;52:402-10.  Back to cited text no. 11
    

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Correspondence Address:
Rajesh Kulkarni
B J Government Medical College, Pune, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0377-4929.138812

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