What lab tests are used to diagnose non-small cell lung cancer (NSCLC)?

Diagnostic Laboratory Tests for Non-Small Cell Lung Cancer (NSCLC)

The diagnosis of non-small cell lung cancer requires tissue sampling through biopsy or cytology procedures, followed by pathological examination and molecular testing. 1 There is no single blood test that can definitively diagnose NSCLC.

Tissue Acquisition Methods

Bronchoscopic Techniques

• Flexible videobronchoscopy with biopsy:
  • For visible endobronchial tumors: At least 5 forceps biopsies recommended (diagnostic yield >85%)
  • For peripheral tumors: Additional 5 biopsies or 2 cryobiopsies may be needed 1
  • Guided techniques (for peripheral lesions):
    • Endobronchial ultrasound (EBUS): At least 4 needle passes per target lesion 1
    • Electromagnetic navigation guidance (if available) 1

Percutaneous Approaches

• CT-guided coaxial core biopsy:
  • Preferred over aspiration cytology
  • At least 2 core needle biopsies using 18-20G needle (3-6 biopsies optimal) 1
  • Diagnostic yield >90% for lesions >15mm near chest wall 1
  • Complications: pneumothorax (1-4% requiring chest tube), hemorrhage 1

Surgical Techniques

• Thoracoscopy/VATS: For difficult-to-reach lesions or when less invasive methods fail
• Mediastinoscopy: For sampling mediastinal lymph nodes
• Thoracotomy: When other methods are non-diagnostic but suspicion remains high 1

Pathological Examination

Histological Classification

• Immunohistochemistry (IHC) to distinguish between:
  • Adenocarcinoma: TTF-1 positive, CEA positive
  • Squamous cell carcinoma: p40, p63, CK5/6 positive
  • Large cell carcinoma: Diagnosis of exclusion
  • Small cell lung cancer: Neuroendocrine markers (chromogranin A, synaptophysin, CD56) 2

Molecular Testing

For adenocarcinoma or NSCLC with adenocarcinoma component, testing should include:

1. EGFR mutation analysis:

   • PCR-based methods
   • Required for determining eligibility for EGFR tyrosine kinase inhibitors 1

2. ALK rearrangement testing:

   • FISH (fluorescence in situ hybridization) - gold standard
   • IHC (immunohistochemistry) - screening method
   • RT-PCR approaches also available 1

3. ROS1 testing:

   • Required for determining eligibility for targeted therapies 1

4. Additional molecular markers (based on availability and clinical context):

   • BRAF, MET, RET, NTRK, HER2 alterations
   • PD-L1 expression (for immunotherapy eligibility)

Liquid Biopsy

• Circulating tumor DNA (ctDNA) testing:
  • Can be used when tissue is insufficient or unavailable
  • High concordance (94.8-100%) with tissue biopsy for guideline-recommended biomarkers 3
  • Faster turnaround time (average 26.8 days faster than tissue biopsy) 3
  • Should be considered complementary to tissue testing, not a complete replacement

Staging Procedures

• CT scan of chest and upper abdomen: Essential for all patients 1
• PET-CT scan: For potentially curable disease 1
• Brain MRI: For clinical stage III planned for definitive treatment 1
• Bone scintigraphy: If bone pain, elevated calcium or alkaline phosphatase 1

Practical Considerations

Sample Adequacy

• Insufficient samples are a common pitfall - ensure adequate tissue for both histological and molecular characterization
• If specimens are inadequate, obtaining a second biopsy is acceptable given the importance of accurate tumor characterization 1

Sample Handling

• Standardized workflow for transportation of samples is essential
• Formalin fixation time: 6-48 hours (critical for DNA quality) 1
• Avoid delays between tissue acquisition and fixation (should be <30 minutes) 1

Reporting

• Molecular pathology reports should clearly communicate results to clinicians
• Integrated reports written by pathologists are preferred over stand-alone reports 1
• Reports should include any limitations or uncertainties in test results 1

Algorithm for Diagnostic Approach

1. Initial imaging (CT chest) to identify suspicious lesion
2. Select least invasive biopsy method based on lesion location:
   • Central lesion → Bronchoscopy with biopsy
   • Peripheral lesion → CT-guided needle biopsy
   • Pleural effusion → Thoracentesis
3. Obtain adequate tissue for both histologic and molecular testing
4. Perform pathological examination for histologic classification
5. Conduct molecular testing for targetable alterations
6. Consider liquid biopsy if tissue is insufficient or unavailable
7. Complete staging with additional imaging as needed

Remember that diagnosis should be established by the least invasive method that will provide adequate tissue for both histologic and molecular characterization, as this information is critical for determining the optimal treatment strategy.