What blood tests are done to screen for hematologic malignancy?

Blood Tests for Screening Hematologic Malignancies

The most essential blood tests for screening hematologic malignancies include a complete blood count (CBC) with differential, peripheral blood smear examination, serum protein electrophoresis, and lactate dehydrogenase (LDH) testing. These form the cornerstone of initial evaluation when a hematologic malignancy is suspected 1.

Primary Screening Tests

Complete Blood Count (CBC) with Differential

• Essential first-line test that can detect abnormalities in all blood cell lines
• Provides quantitative assessment of:
  • Red blood cells (anemia may indicate bone marrow infiltration)
  • White blood cells (leukocytosis or leukopenia)
  • Platelets (thrombocytopenia or thrombocytosis)
  • White blood cell differential (neutrophils, lymphocytes, monocytes, eosinophils, basophils)
  • Presence of immature or abnormal cells

Peripheral Blood Smear Examination

• Critical for morphologic assessment of blood cells
• Can identify:
  • Abnormal cell morphology
  • Presence of blast cells
  • Circulating plasma cells
  • Rouleaux formation (suggestive of plasma cell disorders)
  • Leukemic cells 2

Serum Protein Studies

• Serum Protein Electrophoresis (SPEP) and Immunofixation Electrophoresis (IFE)
  • Essential for detecting monoclonal proteins (M-proteins)
  • Critical for diagnosing plasma cell disorders including multiple myeloma 2
• Quantitative immunoglobulins (IgG, IgA, IgM)
  • Helps identify abnormal immunoglobulin patterns 1
• Serum Free Light Chain Assay
  • Detects excess kappa or lambda light chains
  • Important for diagnosing and monitoring plasma cell disorders 2

Lactate Dehydrogenase (LDH)

• Elevated in many hematologic malignancies
• Serves as both a screening and prognostic marker 1

Secondary and Specialized Tests

Bone Marrow Examination

• Indicated when peripheral blood tests suggest hematologic malignancy
• Includes:
  • Bone marrow aspiration and biopsy
  • Morphologic examination
  • Flow cytometry for immunophenotyping
  • Cytogenetic analysis 2, 1

Cytogenetic and Molecular Studies

• Karyotyping (conventional cytogenetics)
• Fluorescence In Situ Hybridization (FISH)
  • Detects specific chromosomal abnormalities
  • Examples include BCR-ABL1 for CML, KMT2A translocations, ETV6-RUNX1 2, 1
• Molecular genetic testing for specific mutations

Disease-Specific Tests

For Plasma Cell Disorders

• 24-hour urine protein
• Urine Protein Electrophoresis (UPEP)
• Urine Immunofixation Electrophoresis (UIFE)
• Beta-2 microglobulin (prognostic marker)
• Serum calcium and creatinine 2

For Chronic Myeloid Leukemia (CML)

• Basophil count (elevated basophils >0.43 × 10^9/L is highly sensitive for CML)
• Immature granulocyte count
• Neutrophil alkaline phosphatase (NAP) score 2, 3

Algorithmic Approach to Screening

1. Initial Screening: CBC with differential and peripheral blood smear

   • If abnormalities detected → proceed to specialized testing
   • If normal but clinical suspicion remains → consider additional testing

2. For suspected plasma cell disorders:

   • SPEP, IFE, and serum free light chain assay
   • If positive → 24-hour urine studies and bone marrow examination

3. For suspected leukemia:

   • Detailed CBC with attention to blast cells, basophilia, or other abnormal cells
   • If suspicious → immediate bone marrow examination with cytogenetics and flow cytometry

4. For suspected lymphoma:

   • CBC, LDH, and peripheral blood flow cytometry
   • If suspicious → lymph node biopsy and/or bone marrow examination

Important Considerations

• No single blood test can screen for all hematologic malignancies; interpretation requires integration of multiple test results
• Abnormal CBC findings often provide the first clue to hematologic malignancy but require follow-up with more specific tests
• Bone marrow examination remains the gold standard for definitive diagnosis of many hematologic malignancies
• Cytogenetic and molecular studies are increasingly important for diagnosis, classification, and treatment planning

Early detection through appropriate screening can significantly impact morbidity and mortality outcomes in hematologic malignancies by enabling prompt initiation of appropriate therapy.