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Leukemia - Acute

AML not otherwise categorized

Acute myelomonocytic leukemia (FAB AML M4)


Reviewer: Daniela Mihova, M.D (see Reviewers page)
Revised: 6 February 2013, last major update September 2012
Copyright: (c) 2001-2013, PathologyOutlines.com, Inc.

General
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Criteria for diagnosis: myeloblasts, monoblasts and promonocytes are 20% or more of nonerythroid cells; myeloblasts and granulocytes are 80% or less of non-erythroid 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
● See also AML with inv(16)(p13;q22) or t(16;16)(p13;q22)

Clinical features
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● 5-10% of AML cases, 3% of childhood leukemia (Orphanet May 2004)
● 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
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● 15 year old girl with catastrophic antiphospholipid antibody syndrome (J Pediatr Hematol Oncol 2004;26:327)
● 21 year old man with AML mimicking primary testicular neoplasm (Eur J Haematol 2003;70:242)
● 23 year old pregnant woman with CD15, CD33 and HLA-DR+ antibodies (The Internet Journal of Hematology 2003;1:1)
● 27 year old man with leukemic ascites (Arch Pathol Lab Med 2005;129:262)
● 30 year old woman with gingival hyperplasia (Univ Pittsburgh, Case 344)

Micro description
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● 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

Micro images
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Peripheral smear:

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):
             
Mixture of monocytes and neutrophils at  Promonocytes on left have basophilic cytoplasm with
different stages of maturation, also several coarse azurophilic granules; those in upper right have
promonocytes with abundant cytoplasm   abundant pale cytoplasm with delicate nuclear folds
containing fine azurophilic granules and
delicately folded nuclei

             
Three promonocytes have abundant    Five promonocytes and two myelocytes (center),
cytoplasm with fine azurophilic granules,   one containing numerous azurophilic granules and an Auer rod
also dysplastic neutrophil with pseudo-
Pelger-Huet nucleus in upper left

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

Other sites:

Leukemic ascites

Stains:
           
Non-specific esterase  CD68         Lysozyme        Peroxidase (myeloid marker)


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

Flow cytometry description
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Clinical Flow Wiki

Positive stains
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● May vary between monocyte and myeloid populations
● CD4, CD11b, CD11c, CD13, CD14 (possibly), CD15, CD33, CD36, CD64, CD65, CD68, CD71 (variable), CD163, HLA-DR, lysozyme and myeloperoxidase
● Variable CD56, CD34 and CD117 (Am J Clin Pathol 2004;122:865)

Negative stains
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● CD41, CD61, glycophorin A and keratin

Molecular description
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● Non-specific 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
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AML M2
● AML with recurrent genetic abnormalities
● CMML
● G-CSF related transient atypical monocytosis (Clin Lab Haematol 2004;26:359)
● Leukemoid reaction
M5
Microgranular M3
t-AML (therapy related)
Myelodysplastic syndrome
● Sarcomatoid carcinoma

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


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