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Leukemia - Acute

AML not otherwise categorized

Acute megakaryoblastic leukemia (AMKL, M7)

Reviewer: Daniela Mihova, M.D. (see Reviewers page)
Revised: 2 February 2013, last major update September 2012
Copyright: (c) 2001-2013, PathologyOutlines.com, Inc.


● Up to 10% of AML in children, 5% or less of adult AML (Orphanet (May 2004))
● 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


● 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

● 1 year old child with anemia and thrombocytopenia (Univ of Pittsburgh Case #439)
● Child with bi-allelic deletions within 13q14 and transient trisomy 21 with absence of GATA1 (Pediatr Blood Cancer 2011;57:516)
● Young boy with coexisting mediastinal germ cell tumor (Clin Transl Oncol 2007;9:329)
● 25 year old man with findings on FNA and CSF (Cytojournal 2011;8:17)
● 25 year old man with i(12p) related disease after primary mediastinal germ cell tumor (J Korean Med Sci 2011;26:1099)
● 58 year old woman with coexisting myeloid sarcoma of femur (Srp Arh Celok Lek 2011;139:805)
● Diagnosis 15 years after kidney transplantation (Ann Hematol 2011;90:843)
● "Cannibalistic" phagocytosis in acute megakaryoblastic leukemia (AML M7) with t(10;17)(p15;q22) (Leuk Lymphoma 2010;51:1944)
● Coexistence of meningeal infiltration and multiple lymphadenopathy as the initial presentation of de novo adult acute megakaryoblastic leukemia (Leuk Res 2011;35:e50)

Micro 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

Micro images

Bone marrow smears (Wright-Giemsa):

Blasts have abundant cytoplasm

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

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

Bone marrow biopsy:

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

Marked proliferation of megakaryocytes with variation in size and nuclear morphology

CD61                                   (figures C, D)

Reticulin stain shows marked increase in reticulin fibers

CD34-red, podocalyxin-brown    CD42b (figure c)

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

Cytology images


Positive stains

● CD41 and CD61 (megakaryocyte specific), CD42b (Mod Pathol 2005;18:603), CD34, CD36, factor VIII and von Willebrand factor
● Variable CD13, CD33, CD71, alpha naphthyl acetate esterase, PAS and HLA-DR
● Rarely positive for alpha-1-antitrypsin, alpha-1-antichymotrypsin or lysozyme (Am J Surg Pathol 1987;11:883)

Negative stains

● Myeloperoxidase, Sudan Black B, CD14, CD64 and glycophorin A

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

● Blastic transformation of CML
● Metastatic small blue cell tumors in children

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


● Uncommmon; <1% of AML; translocation appears to be specific to AMKL (Atlas of Genetics and Cytogenetics)
● WHO 2008: AML generally showing maturation in the megakaryocyte lineage, with indicated translocation, without Down syndrome
● Infants and young children (<3 years old), usually girls
● Most cases present within first month of life with marked hepatosplenomegaly (Blood 1991;78:748), prominent myelofibrosis, anemia, thrombocytopenia and moderately elevated WBC
● Tissue involvement resembles metastatic tumor
● Poor outcome (Leukemia 2000;14:216); but may respond well to intensive chemotherapy

Case reports

● 1 month old infant with hepatic involvement and no initial marrow involvement (Pediatr Dev Pathol 2008;11:55)
● 9 month old girl with proliferation of erythroid and megakaryocytic lineages (Rinsho Ketsueki 1999;40:230)
● 59 year old man with RBM15-MKL1 (OTT-MAL) fusion transcript (Am J Hematol 2005;79:43)
● Hemophagocytosis by leukemic megakaryoblasts (J Pediatr Hematol Oncol 2012;34:576)

Micro description

● Bone marrow is normocellular to hypercellular with prominent collagenous and reticulin fibrosis; blasts may be spindled and form intertwining bundles resembling metastatic disease (Am J Clin Pathol 1992;98:214)
● If <20% blasts on aspirate smear, check bone marrow for fibrosis which may mask blast count; if blasts are actually <20%, closely monitor for more definitive evidence of AML
● Small and large megakaryoblasts (medium to large with basophilic agranular cytoplasm, possibly with distinct blebs or pseudopods; round slightly irregular nuclei, fine reticular chromatin, one to three nucleoli), micromegakaryocytes, undifferentiated blasts, but no dyserythropoiesis and no dysgranulopoiesis

Micro images

Various images

Positive stains

● CD41+, CD61+ (cytoplasmic CD41 and CD61 more sensitive and specific), CD42+, CD36+; CD13 and CD33 may be positive

Negative stains

● CD34, HLD-DR, CD45
● Cytochemistry: negative for Sudan Black and myeloperoxidase

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

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