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Leukemia - Acute

AML not otherwise categorized

Acute erythroid leukemia (AML-M6)


Reviewer: Daniela Mihova, M.D. (see Reviewers page)
Revised: 2 February 2013, last major update September 2012
Copyright: (c) 2001-2013, PathologyOutlines.com, Inc.

General
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● Includes two subtypes: erythrod / myeloid leukemia (M6a, more common) or pure erythroid leukemia (M6b, rare) (eMedicine)
● One letter suggests that most cases may now be defined as AML with multilineage dysplasia (Haematologica 2004;89:ELT11)


Erythroleukemia (M6a)

General
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● 1% of AML cases
● Children to >age 90, usually adults, male predominance
● 20% of therapy related AML but only 1% of de novo AML
● Much more common than pure erythroid leukemia (Haematologica 2002;87:148)
● Di Guglielmo syndrome: nonspecific clinical findings of anemia, thrombocytopenia, variable neutropenia
● Hemophagocytic lymphohistiocytosis: recurrent and specific complication (Br J Haematol 2011;153:669, Br J Haematol 2011;153:669)
● Rare extramedullary involvement
● Peripheral smear may have prominent erythroblasts

Diagnosis
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● 50%+ of nucleated marrow cells are erythroid lineage, including erythroblasts, 20%+ of nonerythroid cells are myeloblasts (Leuk Lymphoma 2006;47:683)
● Dyserythropoiesis is prominent
● Dysplasia in <50% of cells in only 1 cell lineage
● No MDS/MPN, no erythropoietin, cytotoxic or radiation therapy, no AML or MDS cytogenetic abnormalities, no Ph chromosome or t(9;22)
● May be familial (Br J Haematol 1987;65:313)

Prognostic factors
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● Poor prognosis but better than pure erythroid leukemia (pEL, M6b), better overall survival if non-complex cytogenetic abnormalities
● Treated with bone marrow transplantation

Case reports
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● Congenital erythroleukemia presenting as infantile hemangioma (Plast Reconstr Surg 2007;119:70e)
● 43 year old woman with leukocytosis, congenital disease presenting as liver failure (Arch Pathol Lab Med 2003;127:1362)
● Associated with low dose methotrexate for rheumatoid arthritis (Clin Exp Rheumatol 1999;17:S95)
● KIT(D816V+) systemic mastocytosis associated with KIT(D816V+) acute erythroid leukaemia (J Clin Pathol 2009;62:1147)
● Erythroleukemic infiltration of lymph node (Hum Pathol 1984;15:1090)

Micro description
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● Hypercellular marrow
● Predominance of erythroid precursors with PAS+ cytoplasmic vacuoles (evidence of dysplasia)
● Abnormal nuclear development including megaloblastoid cells, karyorrhexis and gigantoblasts with multiple nuclei
● Often dysplastic platelets and megakaryocytes with megaloblastoid nuclei
● 20%+ nonerythroid cells are myeloblasts, and may have Auer rods
● May have ringed sideroblasts

Micro images
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Bone marrow smear (Wright-Giemsa):

Numerous myeloblasts and erythroid precursors at all stages of maturation

Megaloblastoid erythroblast and three myeloblasts

Multinucleated erythroblast has megaloblastoid chromatin

Acute erythroleukemia


20%+ each of pronormoblasts and myeloblasts (formerly M6c)

Bone marrow biopsy:

Early to late stage erythroblasts, small megakaryocytes at upper and lower margins, marked reduction in granulocytes

Marrow is replaced by blasts with variable size and few mature erythroid forms, immature erythroid cells have dispersed chromatin and prominent nucleoli

Blood smear:

20:1 ratio of erythroid precursors to WBC in asplenic patient with erythroleukemia, most precursors are at polychromatic and basophilic maturation stages

Stains:

Immature erythroid cells are hemoglobin A+

Positive stains
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Erythroid cells: glycophorin A (mature forms), hemoglobin A, CD36, CD71, CD117(dim), PAS (vacuoles), variable MRD-1 and P-glycoprotein (Mod Pathol 2000;13:407)
Myeloid cells : Myeloperoxidase, CD13, CD33, CD36, CD71, CD117, HLA-DR

Negative stains
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Erythroid cells: myeloperoxidase, CD13, CD33, CD34 (or weak), HLA-DR (or weak), CD41 and CD61
● Immature erythroblasts may be negative for hemoglobin A or glycophorin A
Leukemic blasts: loss of inhibin (Arch Pathol Lab Med 2001;125:198)

Flow cytometry description
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Acute Erythroblastic leukemia (M6)

Differential diagnosis
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● AML-M0
● AML with multilineage dysplasia
● B/T ALL
● Burkitt lymphoma
● Congenital dyserythropoiesis
● Megakaryoblastic leukemia (AML M7)
● Megaloblastic anemia
● Myeloproflierative neoplasm with erythroblasts
● Parvovirus infection
● Plasma cell myeloma
● RAEB-2, t-AML and CML with erythroblast phase
● Recurrent genetic abnormalities
● Secondary dyserythropoiesis


Pure erythroid leukemia (M6b)

General
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● Very rare (3% of acute erythroid leukemia cases)
● Also called erythemic myelosis, Di Guglielmo disease syndrome
● Aggressive
● Can be seen in infants
Enzyme cytochemistry: PAS (block-like staining pattern), alpha naphthyl acetate esterase (nonspecific esterase); also acid phosphatase
Prognosis: dismal, worse than erythroid / myeloid leukemia (AML-M6a)

Case reports
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● 51 year old man with pancytopenia (Arch Pathol Lab Med 2004;128:241)
● 58 year old man post-essential thrombocythemia (Am J Hematol 2004;77:140)
● 81 year old man post treatment for myeloma (Arch Pathol Lab Med 2006;130:1075)

Micro description
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● Committed exclusively to erythroid lineage (> 80% of BM cells) with no evidence of a significant myeloblastic component
● Usually proerythroblasts or early basophilic erythroblasts that are medium to large with deeply basophilic cytoplasm containing poorly demarcated vacuoles, often agranular
● Nuclei are round with fine chromatin and 1+ prominent nucleoli
● No apparent myeloid component

Micro images
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Bone marrow smear (Wright-Giemsa):
     
Pure erythroid leukemia  Very large erythroid precursors


Abnormal erythroid precursors at all stages of maturation, granulocyte lineage appears normal


Proerythroblasts and basophilic erythroblasts predominate, many have numerous cytoplasmic vacuoles


Three immature erythroblasts with large, clear cytoplasmic vacuoles


Erythroblasts are intermediate to large with round nuclei, fine chromatin and 1+ prominent nucleoli (fig A), cytoplasmic vacuoles are PAS+ (inset), bone marrow biopsy shows sheets of blasts and occasional multinucleated giant cells (fig B) and inset shows no staining for myeloperoxidase


Fig 1: large cells with deeply basophilic cytoplasm with vacuoles, round nuclei have fine chromatin and single distinct nucleoli; fig 2: PAS shows cytoplasmic block-like staining

Bone marrow biopsy:

Extensive replacement by immature erythroid precursors, with occasional very large abnormal cells

Stains:

Large abnormal cells and others are hemoglobin A+

Positive stains
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● Glycophorin A (mature forms), hemoglobin A, CD36, CD71, MDR1, P-glycoprotein (Mod Pathol 2000;13:407)
● Vacuoles are PAS+

Negative stains
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● Myeloperoxidase, CD13, CD33, CD34 (or weak), HLA-DR (or weak), CD41 and CD61
● Immature erythroblasts may be negative for hemoglobin A or glycophorin A

Molecular description
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● Often complex cytogenetics abnormalities involving #5 and #7

Differential diagnosis
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● AML-M0
● AML-M7
● AML-Myelodysplasia-Related Changes if 5 and 7 chromosomal abnormalities
● B/T ALL
● Congenital dyserythropoiesis
● Parvovirus infection
● Reactive erythroid hyperplasia associated with folate or vitamin B12 deficiency
● Undifferentiated leukemia

End of Leukemia - Acute > AML not otherwise categorized > Acute erythroid leukemia (AML-M6)


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