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Leukemia - Acute

AML not otherwise categorized

Acute monoblastic and acute monocytic leukemia (AML- M5)


Reviewer: Daniela Mihova, M.D. (see Reviewers page)
Revised: 20 February 2013, last major update September 2012
Copyright: (c) 2001-2013, PathologyOutlines.com, Inc.

General
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● 10% of AML cases
● High incidence of bleeding disorders (including DIC), organomegaly, lymphadenopathy, gingival hyperplasia, CNS and other tissue involvement (monocytes infiltrate)
● May present with acute respiratory failure (Am J Respir Crit Care Med 2003;167:1329)
● M5a versus M5b: analysis of features is controversial; (a) similar features (Leuk Res 2008;32:269); (b) different expression of CD68 and CD11c (Zhongguo Shi Yan Xue Ye Xue Za Zhi 2006;14:1079); (c) different features (Zhongguo Shi Yan Xue Ye Xue Za Zhi 2006;14:654)
● Similar prognosis as other subtypes (J Clin Oncol 2004;22:1276)

Criteria for diagnosis
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● 80% or more nonerythroid bone marrow cells are monocyte lineage (monoblasts, promonocytes and monocytes)
● A minor neutrophil component < 20%

Micro images
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Erythrophagocytosis in AML M4/M5 (see cell in upper right)

Enzyme cytochemistry
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● Monoblast granules and monocytes are strongly positive for nonspecific esterase and lysozyme, but negative for myeloperoxidase
● More mature monocyte lineage cells may be weakly myeloperoxidase positive
Note: if NSE negative, confirm monocyte lineage with immunostains

Positive stains
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At least two monocytic markers: CD4, CD14, CD11b (80-90%, Am J Clin Pathol 1997;107:283), CD11c (50%), CD36, CD64 (Am J Clin Pathol 1998;110:797), CD68 and HLA-DR
Myeloid markers: CD13 (often very bright), CD33 (often very bright), CD15 and CD65
● CD34 (30%), CD117 and MPO (more often M5b and less often M5a)
Abberant expression: CD7, CD56 (25-40%)
● Lysozyme, CD68 and CD163

Molecular description
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● 11q23 translocations in 19%, trisomy 8 in 17%


Acute monoblastic leukemia (M5a)

General
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● 5-8% of AML
● Children and young adults

Criteria for diagnosis
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● 80%+ of monocyte lineage cells are monoblasts

Case reports
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● 66 year old man with erythropoietin-dependent transformation of refractory anemia with ringed sideroblasts into acute monoblastic leukemia (Blood 2001;98:3492)
● 73 year old woman with coexisting mantle cell lymphoma (Leuk Lymphoma 2005;46:1813)
● 82 year old man with acute monoblastic leukemia following granular lymphocyte proliferative disorder (Rinsho Ketsueki 2011;52:1870)

Micro description
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● Hypercellular marrow with large number of monoblasts
● Monoblasts are large with moderately abundant intensely basophilic cytoplasm, variably basophilic and delicate azurophilic granules but no/rare Auer rods
● May have pseudopods or vacuoles
● Have round nuclei and lacy chromatin with one or more prominent nucleoli but no folds
● Promonocytes have abundant less basophilic cytoplasm with obvious azurophilic granules and nuclei have delicate folds

Micro images
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Blood smear (Wright-Giemsa):

Two monoblasts (left) have abundant cytoplasm with numerous azurophilic granules, promonocyte (right) has abundant cytoplasm with fine azurophilic granules, nuclei have delicate folds

Bone marrow smear (Wright Giemsa):

Monoblasts are large with abundant cytoplasm containing numerous fine azurophilic granules, nuclei lack folds but have slightly coarse chromatin and 2-3 distinct nucleoli

Some monoblasts also show pseudopods

Monoblasts have variable cytoplasm with mild to intense basophilia, some vacuoles but no granules

Monoblasts are larger cells with abundant cytoplasm and round nuclei, and promonocytes are two cells with folded and creased nuclei next to monoblast in center

Bone marrow and skin

Bone marrow biopsy:

Marrow completely replaced by monoblasts-large cells with abundant cytoplasm, round/oval nuclei with prominent nucleoli

Monoblasts are large with abundant pale cytoplasm, numerous vacuoles and prominent pseudopods, nucleoli are distinct

Monoblasts are large with abundant cytoplasm, some nuclei are irregular, many blasts have single prominent nucleoli

Stains:

Monoblasts are intensely positive for nonspecific esterase

Case also has neoplastic plasma cells

Monoblasts are positive for CD68 #1 (KP-1)

Buffy coat smear-vacuoles are PAS+

Positive stains
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● CD13, CD14 (most), CD68, PAS (vacuoles), nonspecific esterase (strong) and lysozyme

Negative stains
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● Myeloperoxidase

Molecular description
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● 75% have cytogenetics abnormalities, including 11q23 in 30% (these cases should be classified as a recurrent genetic abnormality)
● FLT3 mutations in 7%

Electron microscopy images
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Monoblast stained for nonspecific esterase shows scattered electron-dense deposits indicating enzyme activity

Cytoplasm contains focal area of glycogen deposition, also scattered dense granules and a paranuclear fibrillar array

Differential diagnosis
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ALL-L2
AML-M0
AML-M1
AML-M7
AML-MRC
t-AML
Extramedullary myeloid sarcoma


Acute monocytic leukemia (M5b)

General
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● 3-6% of AML
● Affects all ages
● Mature monocytes or promonocytes predominate in peripheral blood (< 80% of monocyte lineage cells are monoblasts, usually < 20%)
● Treatment may cause tumor lysis syndrome, DIC and falsely elevated platelet counts (Arch Pathol Lab Med 1999;123:1111)

Case reports
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● 47 year old man with spontaneous remission after infection (Int J Lab Hematol 2007;29:386)
● 50 year old man with cutaneous disease, (Arch Pathol Lab Med 2005;129:425)
● 63 year old man with preceding aleukemic leukemia cutis (Case Rep Oncol 2011;4:547)
● 74 year old man with mycosis fungoides now with increased circulating immature mononuclear cells (Univ Pittsburgh case #460)
● 77 year old man with coexisting myeloma (Arch Pathol Lab Med 2003;127:1506)
● With mononucleosis syndrome due to varicella zoster virus (Eur J Haematol 2002;68:236)

Micro description
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● Leukemic cells are often promonocytes with less basophilic cytoplasm and more azurophilic granules than monoblasts
● Have folded or cerebriform nuclei with fine chromatin
● Erythrophagocytosis is common

Micro images
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Blood smears (Wright-Giemsa):

Promonocytes have abundant cytoplasm with azurophilic granules that are myeloperoxidase negative, nuclei have delicate folds, nucleoli are inconspicuous

Bone marrow smears (Wright-Giemsa):

Monocytic cells have range of differentiation, promonocytes have nuclei with delicate folds

Two myeloblasts (round/oval nuclei, high N/C ratio) and three promonocytes (abundant cytoplasm with delicate azurophilic granules, lobulated nuclei with delicate folds)

Bone marrow biopsy:

Cells have moderate granular cytoplasm, nuclei are lobulated and indented with indistinct nucleoli

Treatment:

Before and after treatment, alpha naphthyl butyrate esterase

Stains:

Monocytes and one neutrophil are intensely positive for nonspecific esterase

Skin lesions: H&E and nonspecific (alpha naphthyl butyrate) esterase

Electron microscopy images
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Promonocyte has cytoplasm with numerous small cisternae of rough endoplasmic reticulum and a few scattered dense granules, nucleus is markedly lobulated with marginated chromatin

Positive stains
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● CD13, CD14 (most), CD68, CD61 (some)

Negative stains
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● CD41, glycophorin A

Flow cytometry description
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AMoL (Acute Monoblastic/Monocytic Leukemia) (M5)

Molecular description
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● 30% have cytogenetics abnormalities, including 11q23 in 12% (these cases should be classified as a recurrent genetic abnormality)
● FLT3 mutations in 30%
● t(8;16)(p11;p13) fuses MOZ gene at 8p11 with CBP gene at 16p13 and is associated with erythrophagocytosis and coagulopathy

Differential diagnosis
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AML M4
● Malignant histiocytic disorders
Microgranular acute promyelocytic leukemia
Myelodysplastic syndrome: to distinguish, count promonoblasts in M5 with monoblasts

End of Leukemia - Acute > AML not otherwise categorized > Acute monoblastic and acute monocytic leukemia (AML- M5)


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