How is acute myeloid leukemia (AML) diagnosed?

Diagnosis of Acute Myeloid Leukemia (AML)

The diagnosis of AML requires examination of peripheral blood and bone marrow samples with a comprehensive workup comprising morphological examination, cytochemistry, immunophenotyping, cytogenetic and molecular genetic analysis. 1

Diagnostic Approach

Initial Evaluation

• Peripheral blood examination:

  • Complete blood count with differential
  • Examination for presence of blast cells
  • Note: While peripheral blood can be used for initial diagnosis when blasts are present, bone marrow evaluation remains the gold standard 2

• Bone marrow examination:

  • Bone marrow aspirate for morphological assessment
  • Bone marrow core biopsy for architecture and cellularity
  • Collection of adequate samples for all necessary diagnostic tests 3

Essential Diagnostic Tests

1. Morphological examination:

   • Assessment of blast percentage (≥20% blasts required for traditional AML diagnosis)
   • Note: Some genetic subtypes now require only ≥10% blasts 4
   • Evaluation of dysplastic features in other cell lines

2. Cytochemistry:

   • Myeloperoxidase staining
   • Sudan Black B
   • Non-specific esterase
   • Specific esterase

3. Immunophenotyping:

   • Flow cytometry to identify myeloid markers (CD13, CD33, CD117)
   • Lineage-specific markers to rule out other acute leukemias
   • Aberrant marker expression patterns

4. Cytogenetic analysis:

   • Karyotyping to identify chromosomal abnormalities
   • Detection of recurrent translocations: t(15;17), t(8;21), t(16;16)
   • Identification of complex karyotypes or other adverse cytogenetic features

5. Molecular genetic testing:

   • Detection of mutations in genes such as NPM1, FLT3, CEBPA
   • Identification of mutations in TP53, IDH1/2, and other prognostic markers
   • Next-generation sequencing panels for comprehensive mutational profiling 5

Risk Assessment

Risk assessment in AML is critical for treatment planning and includes:

• Patient factors:

  • Age (patients >60 years have worse prognosis)
  • Performance status
  • Comorbidities (diabetes, heart disease) 1

• Disease factors:

  • Initial leukocyte count
  • AML subtype according to WHO/ICC classification
  • Cytogenetic abnormalities:
    • Favorable: t(15;17), t(8;21), t(16;16)/inv(16) 1
    • Adverse: Complex karyotype, monosomies

• Molecular markers:

  • Favorable: NPM1 mutation (without FLT3-ITD), CEBPA biallelic mutations
  • Adverse: FLT3-ITD, TP53 mutations 1, 4

Additional Evaluations

• Coagulation screening: Essential before central line placement and to detect leukemia-related coagulopathy (particularly important in APL) 1

• HLA typing: For patients who are candidates for allogeneic stem cell transplantation 1

• Imaging studies: If infection is suspected:

  • Thoracic CT scan
  • Abdominal ultrasound or CT scan 1

• Cardiac evaluation: Including echocardiography for patients with cardiac risk factors or history of heart disease 1

Diagnostic Pitfalls to Avoid

1. Inadequate sampling: Ensure sufficient material is collected for all required tests at initial diagnosis to avoid repeat procedures 2

2. Delayed cytogenetic and molecular testing: These are essential for risk stratification and treatment planning and should be expedited 5

3. Missing antecedent hematologic disorders: History of myelodysplastic syndrome affects classification and prognosis 6

4. Overlooking germline predisposition: Certain mutations may indicate inherited forms of AML requiring family screening 2

5. Premature treatment initiation: Chemotherapy should be postponed until all diagnostic material has been collected 1

The diagnostic process for AML has evolved significantly with the incorporation of molecular testing, which has refined classification systems and improved risk stratification. Timely and comprehensive diagnostic evaluation is critical for optimal treatment planning and patient outcomes.