Leukemia - Acute
AML not otherwise categorized
Acute megakaryoblastic leukemia (AMKL, M7)

Author: Daniela Mihova, M.D. (see Authors page)

Revised: 6 April 2018, last major update February 2013

Copyright: (c) 2001-2018, PathologyOutlines.com, Inc.

PubMed Search: Acute megakaryoblastic leukemia AMKL M7

Related Topics: Acute megakaryoblastic leukemia with t(1;22)(p13;q13); RBM15-MKL1

Cite this page: Mihova, D. Acute megakaryoblastic leukemia (AMKL, M7). PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/leukemiaM7.html. Accessed July 21st, 2018.
Definition / general
  • Up to 10% of AML in children, 5% or less of adult AML (Orphanet (May 2004): Acute megakaryoblastic leukemia [Accessed 6 April 2018])
  • See also Myeloid leukemia associated with Down syndrome
  • Associated with marrow fibrosis due to megakaryoblast secretion of fibrogenic cytokines, which makes marrow aspiration difficult
  • In adults, median age 57 years, 59% have prior hematologic disorder or myelodysplastic syndrome (Blood 2006;107:880)
  • 19% had prior chemotherapy, classify now as AML-MRC (myelodysplasia related changes) or t-AML
  • Survival: poor, median overall survival is 6 months
  • Peripheral blood: often contains micromegakaryocytes and atypical platelets
  • Down Syndrome (DS): 150x increased risk of AML compared to non-Down children age 0 - 4 years; 70% are AML M7 compared to 3 - 6% in non-Down children
  • DS children ages 0 - 3 years: ALL vs AML risk is 1:1.2 compared to 4:1 for non-DS children
Clinical features
  • Thrombocytopenia, may have thrombocytosis, dysplastic features in neutrophils, erythroids, megakaryocytes and platelets
  • Infrequent hepatosplenomegaly
  • Associated with germ cell tumors in young boys
Diagnosis
  • WHO 2008: 20%+ blasts
  • 50%+ blasts of megakaryocytic lineage are present in bone marrow
  • Must exclude AML-MRC (myelodysplasia related changes), AML with t(1;22)(p13;q13); inv(3)(q21;q26.2); t(3;3)(q21;q26.2) and Down syndrome related
  • Megakaryocytic lineage is based on CD41+, CD61+ or positive platelet peroxidase reaction on EM
Case reports
Microscopic (histologic) description
  • Megakaryoblasts (often better morphology on biopsy than smear) are medium / large cells with blue vacuolated, agranular, eosinophilic cytoplasm containing fine granules, cytoplasmic projections (blebs and pseudopods) resembling platelets, irregular cytoplasmic borders and cytoplasmic zoning; may occur in clusters
  • Nuclei are round or slightly indented with finely reticular, dense chromatin and 1 - 3 nucleoli
  • Myelofibrosis or increased marrow reticulin is common; may also have small lymphoid-like blasts
Microscopic (histologic) images

Images hosted on PathOut server:

Bone marrow smears (Wright-Giemsa):
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Blasts have abundant cytoplasm

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Promegakaryocytes (larger than blasts,
cytoplasmic budding, irregular nuclei,
coarse chromatin) and large blasts

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Touch prep shows 3 blasts with
basophilic cytoplasm, coarse
chromatin and distinct nucleoli


Bone marrow biopsy:
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Extensive infiltration by blasts with sparse
cytoplasm, frequent convoluted nuclei
with fine chromatin and distinct nucleoli

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Marked proliferation of megakaryocytes with
variation in size and nuclear morphology


Stains:
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Reticulin stain shows marked increase in reticulin fibers

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PAS+ large megakaryocytes and micromegakaryocytes,
also immature cells and erythrocyte precursors



Images hosted on other servers:

Bone marrow biopsy:
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Extensive infiltration by blasts with sparse
cytoplasm, frequent convoluted nuclei
with fine chromatin and distinct nucleoli


Stains:
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CD61

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(figures C, D)

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CD34-red, podocalyxin-brown

Cytology images

Images hosted on other servers:
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FNA and CSF

Electron microscopy description
  • Megakaryoblasts have demarcation membranes and “bulls-eye” alpha granules with peroxidase activity in nuclear envelope and endoplasmic reticulum, but not in granules and Golgi complex
Differential diagnosis