Leukemia - Acute
AML not otherwise categorized
Acute myelomonocytic leukemia (FAB AML M4)

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

Revised: 4 April 2018, last major update November 2014

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

PubMed Search: Acute myelomonocytic leukemia [title] FAB AML M4

Related Topics: AML with inv(16)(p13.1;q22) or t(16;16)(p13.1;q22)

Cite this page: Mihova, D. Acute myelomonocytic leukemia (FAB AML M4). PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/leukemiaM4.html. Accessed August 17th, 2018.
Definition / general
  • Criteria for diagnosis: myeloblasts, monoblasts and promonocytes are 20% or more of nonerythroid cells; myeloblasts and granulocytes are 80% or less of nonerythroid cells; monocyte lineage cells are 20% or more of nonerythroid bone marrow cells
  • If less than 20% of bone marrow cells are monocyte lineage, still M4 if blood monocyte count is 5x109/L or higher
  • Additional criteria (if cannot distinguish early monocytes and early granulocytes): nonspecific esterase reactivity in 20% or more cells or serum lysozyme of 3 times normal
Clinical features
  • 5 - 10% of AML cases, 3% of childhood leukemia (Orphanet May 2004: Acute myelomonocytic leukemia [Accessed 4 April 2018])
  • Children and adults; more common in adults; median age 50 years; male:female is 1.4:1
  • Often markedly elevated WBC with anemia and thrombocytopenia, fever, fatigue, variable blasts and promonocytes in peripheral blood; organomegaly, lymphadenopathy and other tissue infiltration (monocytes infiltrate)
  • May occur post-therapy (Sichuan Da Xue Xue Bao Yi Xue Ban 2007;38:347)
  • Enzyme cytochemistry: monoblasts, promonocytes and monoctes are positive for nonspecific esterase; if negative, confirm monocyte lineage with immunophenotyping or EM; at least 3% of blasts are MPO+; double staining for NSE and CAE or MPO may show dual positive cells
Case reports
Microscopic (histologic) description
  • Myelocytic and monocytic differentiation evident
  • Myeloid cells resemble M2 (60% of myeloblasts have Auer rods), but at least 20% of nonerythroid cells are of monocytic lineage
  • Monoblasts are large cells with abundant cytoplasm, moderately to intensely basophilic, may have pseudopod formation, scattered fine azuophilic granules and vacuoles
  • Round nuclei with lacy chromatin and one or more large nucleoli
  • Promonocytes have abundant, less basophilic cytoplasm which is more obviously granulated with occasional large azurophilic granules and vacuoles, is more irregular and has delicately folded nuclei
Microscopic (histologic) images

Images hosted on PathOut server:
Peripheral smear:
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Myeloblast (upper left) with two long slender Auer rods, neutrophilic myelocyte (below myeloblast) with smudged nonspecific
granules and promonocyte (right) with abundant azurophilic granules and nucleus with delicate folds and creases



Bone marrow smears (Wright-Giemsa):
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Mixture of monocytes and neutrophils at
different stages of maturation, also several
promonocytes with abundant cytoplasm
containing fine azurophilic granules and
delicately folded nuclei

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Promonocytes on left have basophilic cytoplasm with
coarse azurophilic granules; those in upper right have
abundant pale cytoplasm with delicate nuclear folds


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Three promonocytes have abundant
cytoplasm with fine azurophilic granules,
also dysplastic neutrophil with pseudo-
Pelger-Huet nucleus in upper left

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Five promonocytes and two myelocytes (center),
one containing numerous azurophilic granules and an Auer rod



Bone marrow biopsy:
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Markedly hypercellular marrow with heterogeneous cells, including
immature monocytes (irregular nuclei and prominent nucleoli) and neutrophils



Stains:
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Chloroacetate esterase stains neutrophils blue,
and nonspecific esterase stains monocytes red-brown



Images hosted on other servers:

Bone marrow biopsy:
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Resembling sarcomatoid carcinoma



Other sites:
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Leukemic ascites



Stains:
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Nonspecific esterase

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CD68

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Lysozymes

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Peroxidase (myeloid marker)

Flow cytometry description
Positive stains
Negative stains
Molecular / cytogenetics description
  • Nonspecific cytogenetic abnormalities, +8 in most cases
  • Classify as AML with recurrent genetic abnormalities if inv(16)(p13;1q22), t(16;16)(p13.1q22) or t(9;11)(p22;q23) present
Differential diagnosis