Diagnostic Criteria for Acute Myeloid Leukemia (AML)

Key Diagnostic Threshold

• The American Society of Hematology recommends that AML requires ≥20% blasts in bone marrow or peripheral blood, except for specific recurrent genetic abnormalities where any blast percentage suffices for diagnosis 1, 2, 3, 4

Primary Differential Diagnoses

Acute Lymphoblastic Leukemia (ALL)

• The National Comprehensive Cancer Network suggests that ALL is distinguished by lymphoid lineage markers rather than myeloid markers 1
• ALL blasts express CD19 (strong) with CD79a, cCD22, or CD10 for B-lineage, or cytoplasmic/surface CD3 for T-lineage 2, 3
• The American College of Pathology recommends that critical distinction is made between AML blasts expressing myeloperoxidase (MPO) or monocytic markers, while ALL blasts do not 1, 2

Myelodysplastic Syndromes (MDS)

• The International Society for Experimental Hematology states that MDS has <20% blasts in bone marrow or peripheral blood, which is the defining distinction from AML 7

Mixed Phenotype Acute Leukemia (MPAL)

• The World Health Organization recommends that MPAL expresses markers of both myeloid and lymphoid lineages on the same blast population or separate blast populations 1, 2
• For myeloid lineage assignment in MPAL, requires MPO or at least 2 monocytic markers (NSE, CD11c, CD14, CD64, lysozyme) 2, 3

AML with Myelodysplasia-Related Changes

• The American Society of Clinical Oncology suggests that AML with myelodysplasia-related changes is diagnosed when AML (≥20% blasts) occurs with prior history of MDS or MDS/MPN, or myelodysplasia-related cytogenetic abnormalities, or multilineage dysplasia in ≥50% of cells in 2+ lineages 1, 7

Essential Diagnostic Workup

Morphology and Cell Counts

• The College of American Pathologists recommends counting 200 leukocytes on peripheral blood smears and 500 nucleated cells on bone marrow smears 2, 4
• Include myeloblasts, monoblasts, and megakaryoblasts in blast count 4

Immunophenotyping Markers

• The American Society for Clinical Pathology suggests that for AML diagnosis, precursor markers include CD34, CD38, CD117, CD133, HLA-DR 1, 2, 3
• Granulocytic markers include CD13, CD15, CD16, CD33, CD65, cytoplasmic MPO 4

Cytogenetic and Molecular Analysis

• The National Cancer Institute recommends that recurrent genetic abnormalities define specific AML subtypes regardless of blast percentage 1, 3

Common Pitfalls to Avoid

• The American Society of Hematology warns against diagnosing AML based solely on blast percentage without immunophenotyping—MPAL and ALL can present with similar blast counts but require different treatment 1, 2
• Do not count mature monocytes as blasts in monocytic AML—only monoblasts and promonocytes count 4
• Do not overlook prior MDS or chemotherapy history—these change the AML classification to specific subtypes with different prognoses 7