Bone marrow neoplastic

Bone marrow - neoplastic myeloid

AML not otherwise specified


Last author update: 21 March 2023
Last staff update: 21 March 2023

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PubMed Search: Acute myelomonocytic leukemia

Ramya Gadde, M.D.
Rose Beck, M.D., Ph.D.
Page views in 2022: 9,753
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Cite this page: Gadde R, Beck R. AMML. website. Accessed June 1st, 2023.
Definition / general
  • As per the current 5th edition of WHO classification (2022), acute myelomonocytic leukemia (AMML) is a distinct entity within acute myeloid leukemia (AML), defined by differentiation category (Leukemia 2022;36:1703)
  • Acute myeloid leukemia, not otherwise specified (AML, NOS) according to the International Consensus Classification (ICC)
Essential features
  • Acute myelomonocytic leukemia shows evidence of both granulocytic and monocytic differentiation
  • Does not meet the criteria for inclusion in any of the other AML groups
  • Blasts / blast equivalents include myeloblasts, monoblasts and promonocytes and must comprise at least 20% of blood or bone marrow cells
  • Granulocytic differentiation is present but cells of monocytic lineage must be at least 20% of cells
  • AML M4 (FAB)
  • AMMoL
  • AMML
ICD coding
  • ICD-10: C92.5 - acute myelomonocytic leukemia
  • ICD-11: 2A60.33 - acute myelomonocytic leukemia
  • Proliferation of a malignant hematopoietic stem cell which retains the capacity to differentiate into both granulocytic and monocytic cells
  • Genetic drivers of AML include both chromosomal alterations and gene mutations
  • Exact causes are unknown
Clinical features
  • Signs and symptoms relate to anemia, thrombocytopenia and increased number of infections
    • Early symptoms include fever, fatigue, weakness, weight loss, shortness of breath
    • Also can present as organomegaly, lymphadenopathy and other tissue infiltration (monocytic infiltrate)
  • Reference: Curr Oncol 2022;29:6245
  • Diagnosis is based on integration of morphology, immunohistochemistry, cytochemistry, flow cytometry studies, cytogenetics and molecular findings
  • Immunophenotyping is useful to confirm that both myeloid and monocytic populations are present
  • Genetic testing excludes AML with recurrent genetic abnormalities which have myelomonocytic morphology
  • Criteria for diagnosis:
    • Blasts / blast equivalents comprise ≥ 20% of bone marrow cells
      • Blasts / blast equivalents include myeloblasts, monoblasts and promonocytes
      • Cells of monocytic lineage (monoblasts, promonocytes, monocytes) overall comprise at least 20% of cells
    • AMML is similar to but distinct from acute monoblastic / monocytic leukemia, which requires ≥ 80% of blasts / blast equivalents to be of monocytic lineage
    • Additional criteria: ≥ 3% of blasts should be positive for MPO by cytochemical stain (indicates myeloid lineage)
      • Monocytic lineage may be ascertained by nonspecific esterase stain (not always present) or monocytic immunophenotype (e.g., expression of CD14, CD11c, CD64, CD163, lysozyme)
    • No recurrent genetic abnormalities identified (Leukemia 2022;36:1703)
      • AMML of AML, defined by differentiation, morphologically resembles AML with CBFB::MYH11 fusion (formerly known as FAB M4Eo), AML with KMT2A rearrangement and some cases of AML with NPM1 mutation
  • Leukocytosis is common
  • Anemia, thrombocytopenia
Prognostic factors
  • Poor prognostic factors:
    • Adverse mutation profile, including wild type NPM1 and FLT3 ITDhigh, mutated RUNX1 and mutated TP53 (Am J Hematol 2018;93:1267)
    • Complex karyotype
Case reports
  • Standard induction chemotherapy with cytarabine given twice daily for 10 days combined with an anthracycline drug for 3 days
  • Consolidation therapy often with higher doses of same drugs used for induction or an allogenic stem cell transplant
  • Targeted therapy if respective mutations are present (e.g., FLT3 or IDH1 / IDH2 inhibitors)
  • Reference: Curr Oncol 2022;29:6245
Microscopic (histologic) description
  • By definition, blasts and blast equivalents comprise at least 20% of cells in marrow or blood, while cells of monocytic lineage (monoblasts, promonocytes and monocytes) are also at least 20% of cells
  • Myeloblasts have high N:C ratios, round nuclei and variably granular cytoplasm; Auer rods occasionally seen
  • Monoblasts are large cells with abundant, moderately to intensely basophilic cytoplasm
    • May have pseudopod formation, scattered fine azurophilic granules and vacuoles
    • Often with round nuclei with lacy chromatin and one or more large nucleoli
  • Promonocytes have more irregular nuclei, typically with delicate folds and abundant, less basophilic cytoplasm which is more obviously granulated with occasional large azurophilic granules and vacuoles
  • Reference: Haematologica 2009;94:994
Microscopic (histologic) images

Contributed by Ramya Gadde, M.D., Rose Beck, M.D., Ph.D. and AFIP

Increased myelomonocytic population

Lysozyme immunostain

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Bone marrow biopsy

Cytology images

Contributed by Ramya Gadde, M.D., Rose Beck, M.D., Ph.D. and AFIP

Increased blasts and blast equivalents

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Mixture of monocytes and neutrophils

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Promonocytes and dysplastic neutrophil

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Promonocytes and myelocytes

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Chloroacetate and nonspecific esterase stains

Peripheral smear description
  • Peripheral blood often has leukocytosis with blasts, may show increased monocytes and is often more mature than the monocytic cells observed in bone marrow
Peripheral smear images

AFIP images
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Myeloblast, neutrophilic myelocyte and promonocyte

Positive stains
Negative stains
Flow cytometry description
Flow cytometry images

Contributed by Ramya Gadde, M.D. and Rose Beck, M.D., Ph.D.

Blast and monocytic population

Molecular / cytogenetics description
  • Nonspecific cytogenetic abnormalities in most cases, such as +8, monosomy 7 or del (7q), monosomy 5 or del(5q)
Sample pathology report
  • Bone marrow, core biopsy with touch imprint, clot section, aspirate smears, left iliac crest:
    • Acute myelomonocytic leukemia (see comment)
    • Comment: Hypercellular bone marrow for age (80 - 90%) with involvement by acute myeloid leukemia, defined by differentiation. Immature myelomonocytic cells are increased. Erythroid precursors are decreased. Mature myeloid cells are decreased. Megakaryocytes are adequate and appear normal in morphology.
    • Bone marrow aspirate smear is adequate. Blasts / blast equivalents including myeloblasts, monoblasts and promonocytes are increased (50%). Megakaryocytes are adequate in number and show normal morphology.
    • Flow cytometry studies demonstrate an abnormal myeloid blast population with expression of dim CD45, CD34, CD15 (subset), CD33, CD13, HLA-DR and CD117. There is also an immature monocytic population with CD64, CD11b, CD11c, CD13, CD14, CD33 and CD64 expression.
Differential diagnosis
Board review style question #1

What is the most likely overall morphology seen in this bone marrow?

  1. Acute myelomonocytic leukemia
  2. Acute promyelocytic leukemia
  3. AML with maturation
  4. AML without maturation
Board review style answer #1
A. Acute myelomonocytic leukemia

Comment Here

Reference: AMML
Board review style question #2
In acute myelomonocytic leukemia (AMML), flow cytometry would most likely show a blast population that has which of the following expression profiles?

  1. CD34+, CD117+, CD33+, HLA-DR+
  2. CD34-, CD117+, CD33+, HLA-DR-
  3. CD34-, CD117-, CD14+, CD33+, HLA-DR+
  4. CD34+, CD117+, CD33+, HLA-DR+ (myeloblast population) and CD34-, CD117-, CD14+, CD33+, HLA-DR+ (monocytic population)
Board review style answer #2
D. CD34+, CD117+, CD33+, HLA-DR+ (myeloblast population) and CD34-, CD117-, CD14+, CD33+, HLA-DR+ (monocytic population)

Comment Here

Reference: AMML
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