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ASH Image Bank (2001); doi:10.1182/ashimagebank-2001-100184
Copyright © 2001 by the American Society of Hematology.
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Full Case Study

Acute Megakaryoblastic Leukemia

John Lazarchick, M.D.

Medical University of South Carolina



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Figure 1. Marrow aspirate smear showing three megakayroblasts with cytoplasmic pseudopod formation and granular basophilic area in the cytopalsm.

 


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Figure 2. Flow cytometric analysis showed the blasts To positive only for dim CD45 (A) and for dim CD 45 (not shown). All myeloid and lymphoid markers tested were negative. Megakaryocytic markers were not available.

 


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Figure 3. Marrow biopsy showing blasts with prominent nucleoli. Cytoplasmic borders are ill-defined. Mature megakaryocytes are not present.

 


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Figure 4. Immunohistochemical stain of marrow biopsy for von Willebrand Factor antigen demonstrates essentially all of the blast to be positive, consistent with the diagnosis of acute megakaryoblastic leukemia.

 


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Figure 5. Reticulin stain on the marrow biopsy shows increased reticulin consistent with marked marrow fibrosis.

 


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Figure 6. Glycophorin A stain of the marrow showing paucity of erythroid presursors. Most of the positive cells noted are mature red blood cells (RBCs).

 


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Figure 7. Karyotype analysis performed is illustrated. There were 16 normal metaphases and 6 abnormal metaphases. 48,XY,del(9)(p13),add(11)(q24),+19[1]/50,idem+19,+22[5] and 46,XY[16].

 

    Clinical Summary
 TOP
 Clinical Summary
 Diagnosis
 Discussion
 Differential Diagnosis
 
A 3-year-old Hispanic boy was seen by his pediatrician for evaluation of multiple bruises on his thorax and extremities. The patient and his family have no history of a bleeding diathesis.  The child’s parents were unaware of any recent fever, cough, or diarrhea.  The child was not taking any medications except for vitamin tablets.

His vital signs showed a temperature of 100.4 F and a heart rate of 110.  He was normally developed for his age.

Small shotty nodes were palpable in the cervical, axillary, and inguinal areas.  The spleen was palpable 3cm below the left costal margin; the liver edge was 1cm below the right costal margin. Multiple ecchymotic areas of variable resolution were present on the thorax and extremities.

Lab: Hemoglobin (Hgb) 10.6g/dL, white blood cells (WBC) 4400 ( 2 blasts noted), platelets 43,000/uL.  Lactate dehydrogenase (LDH) 696.  Prothrombin time, partial thromboplastin time, and fibrinogen were normal.

Sex
Male

Age
3

Ethnicity
Hispanic


    Diagnosis
 TOP
 Clinical Summary
 Diagnosis
 Discussion
 Differential Diagnosis
 
Course: A diagnosis of acute megakaryoblastic leukemia presenting with pancytopenia was made and the child was started on induction therapy. He has two older siblings who will be considered for allogeneic bone marrow transplantation if his induction phase is successful.


    Discussion
 TOP
 Clinical Summary
 Diagnosis
 Discussion
 Differential Diagnosis
 
Acute megakaryoblastic leukemia (AML) is an uncommon acute leukemia comprising approximately 10% of pediatric and 5% of adult acute myelogenous leukemias.  In the FAB classification scheme it is designated as M7 and in the World Health Organization (WHO) classification as acute megakaryoblastic leukemia.  In children its incidence is highest among infants with Down syndrome (trisomy 21) and has been linked to children with mediastinal germ cell tumors.  Chromosomal abnormalities are unusual except for t(1:22)(p13q13) noted in infants in which there is a stromal pattern of bone marrow infiltration that may mimic a metastatic tumor.  The blasts vary in size from small to large and may have distinct blebs with deeply basophilic cytoplasm that is granular.  Circulating micromegakaryo-blasts may be seen on examination of the peripheral smear. Blasts tend to be clustered on bone marrow preparations. Characteristically, the blasts are myeloperoxidase negative both by histochemical and immunohistochemical staining, but stain positive for platelet-specific markers CD41 (glypcoprotein IIb/IIIa) and CD61 (glycoprotein IIIa) and for von Willebrand factor antigen.  Immunophenotypically, these cells are positive for CD45, CD34, CD41, CD61, and TdT.  Myeloid markers CD33 and 13 are common.  Lymphoid markers, with the exception of CD2 and CD7, are not found.

Cytopenias, particularly thrombocytopenia, are common at presentation but the platelet count can be normal or even increased.  Serum LDH levels are increased.  Marrow fibrosis is often present and may be extensive frequently resulting in difficulty obtaining an aspirate.

Hemorrhagic manifestations are related to the degree of thrombocytopenia and can be readily managed with platelet transfusion therapy.  The prognosis in both children and adults with this form of leukemia is poor.  Approximately 50% of patients will obtain an initial remission with cytarabine and an anthracycline but median survival is only 10.5 months. The prognosis in children with associated Down syndrome is better but few survive more than 3 years.  The role of bone marrow transplantation is uncertain at this time.


    Differential Diagnosis
 TOP
 Clinical Summary
 Diagnosis
 Discussion
 Differential Diagnosis
 
Children - acute undifferentiated leukemia, acute myeloblastic leukemia, acute lymphoblastic leukemia, metastatic neuroblastoma

Adults - minimally differentiated AML, acute panmyelosis with myelofibrosis,  blastic transformation of CML


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Related ASH-SAP Chapter:space logo
Chapter 10: Acute myeloid leukemia

This Article
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Right arrow Articles by Lazarchick, J.
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Right arrow Platelet Disorders - Quantitative Abnormalities - Mucocutaneous hemorrhage
Right arrow Related ASH-SAP Chapter
Right arrowRelated Image Bank Image Sets
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Copyright © 2001 by the American Society of Hematology.