University of Virginia Health System

Acute Megakaryoblastic Leukemia
(M7 AML)

(a) M7 AML- Bone marrow aspirate smear, Wright-Giemsa stain, 1000x

 
(b) M7 AML evolving from myelofibrosis- Bone marrow aspirate smear, Wright-Giemsa stain, 1000x

Description:

Represents up 5% of all cases of AML. The morphology of the proliferating clonal blasts is quite variable ranging from a predominance of microblasts resembling lymphoblasts with irregular cytoplasmic blebs and membrane projections and fine cytoplasmic granules (micromegakaryoblastic subtype) (a) to a very heterogenous population of blasts including large megakaryoblasts with very blue cytoplasm, with or without nuclear lobation and cytoplasmic granules. A mixture of these various morphologic forms is often seen. On a biopsy specimen, fibrosis, ranging from reticulin to colagenous fibrosis is usually seen. Attempts to aspirate a bone marrow sample often results in a "dry tap". The entity referred to as acute panmyelosis or acute myelofibrosis represents a variant of acute megakaryoblastic leukemia in some instances. Acute megakaryoblastic leukemia is probably the most common subtype that emerges from chronic myeloproliferative disorders, especially primary myelofibrosis (b) and essential thrombocythemia. Similar to M6 AML there is an association with mediastinal germ cell tumors in young males. An increased incidence of this subtype is also seen in Down's syndrome.

Cytochemistry:

May show positivity with acid phosphatase, PAS and NSE stains. Myeloperoxidase and Sudan black B stains are negative.

Immunophenotype:

• Stem cell and hematopoietic progenitor markers- CD34- and HLA-DR-; a unique feature is that the leukocyte common antigen (CD45) is negative
• Megakaryocyte lineage markers- CD41 (glycoprotein IIb/IIIa) and/or CD61 (glycoprotein IIIA) usually positive. CD36 (glycoprotein IIIb) is positive.
• Myeloid lineage markers- CD13 and CD33 may be positive

Cytogenetics:

No signature cytogenetic abnormality has been identified. In infants under one year of age the t(1;22) often is present.

Differential Diagnosis:

1. ALL, L1 and L2 subtypes: may require immunophenotyping to distinguish, especially since reticulin fibrosis is common in ALL
2. M2 AML: usually when the blasts are small with type II morphology
3. Acute panmyelosis: since many of these probably represent M7 AML, differentiation may not be possible
4. Small blue cell, non-hematologic tumors metastatic to bone marrow, (e.g. small cell lung cancer, neuroblastoma)- Immunophenotyping is necessary to distinguish
5. In cases in which the large, atypical megakaryoblasts predominate, other tumors (e.g. carcinomas, sarcomas) may also require immunohistochemistry to distinguish.

Clinical and Laboratory Manifestations:

In addition to those associated with acute leukemia in general, splenomegaly is a frequent finding in those that evolve from one of the chronic myeloproliferative disorders, especially primary myelofibrosis with myeloid metaplasia. In these patients a variable leukopenia and anemia is present, but the platelet count may be high, normal or low with increased numbers of large and atypical platelets seen. A leukoerythroblastic peripheral blood picture, often with teardrop red cells usually is present in this setting. In contrast, in those cases that occur de novo (acute panmyelosis with myelofibrosis), splenomegaly usually is not seen, and teardrop red cells are less conspicuous.

Prognosis:

Poor in most cases. In some cases, particularly those emerging from a chronic myeloproliferative disorder the course may be chronic, up to years. Even in de novo cases the disease may smolder for many months with supportive care only.

General References:

• Jaffe ES, Harris NL, Stein H, Vardiman JW, eds. Pathology and genetics of tumors of hematopoietic and lymphoid tissues. Vol. 3 of World Health Organization classification of tumors, Lyon, France: IARC Press, 2001
• Jacobs P, Roux I, Jacobs L: Megakaryoblastic transformation in myeloproliferative disorders. Cancer 54: 297, 1984
• Alhole UH, Razzouk BI, Raimondi SC, et al: Biology and outcome of childhood acute megakaryoblastic leukemia: A single institution's experience. Blood 97:3727, 2001
• Pagano L, Pulsoni A, Vignetti M, et al: Acute megakaryoblastic leukemia: Experience of GIMEMA trials. Leukemia 16:1622, 2002

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