What is the recommended workup for lymphadenopathy?

Recommended Workup for Lymphadenopathy

The recommended workup for lymphadenopathy should include a risk-stratified approach starting with thorough history and physical examination, basic laboratory tests (CBC with differential, ESR, LDH, liver/renal function, HIV testing), ultrasound as first-line imaging, and proceeding to tissue sampling (FNAC, core biopsy, or excisional biopsy) for persistent or concerning lymphadenopathy. 1

Initial Assessment

Risk Factors for Malignancy

• Age >40 years
• Male sex
• White race
• Supraclavicular location
• Systemic symptoms (fever, night sweats, weight loss)
• Duration ≥2 weeks or uncertain duration
• Fixed to adjacent tissues
• Firm consistency
• Size >1.5 cm
• Ulceration of overlying skin 1, 2

Physical Examination

• Document location and characteristics of lymphadenopathy
• Note that palpable supraclavicular, popliteal, and iliac nodes are always abnormal
• Epitrochlear nodes >5 mm are abnormal
• Evaluate for signs of infection (warmth, erythema, tenderness) 1

Diagnostic Algorithm

Step 1: Classify as Localized or Generalized

• Localized: Single region involved
• Generalized: Two or more regions involved (suggests systemic disease) 2, 3

Step 2: Laboratory Testing

• Complete blood count with differential
• Erythrocyte sedimentation rate (ESR)
• Serum lactate dehydrogenase (LDH)
• Liver and renal function tests
• Hepatitis B and C testing
• HIV testing (especially in high-risk patients) 1

Step 3: Imaging

• Ultrasound as first-line imaging modality
  • Assess size and morphology
  • Evaluate presence/absence of hilum
  • Document vascularity patterns
  • Look for extracapsular spread 1
• Advanced imaging (CT or PET-CT) when:
  • Malignancy is suspected
  • Need to evaluate extent of disease
  • Need to assess deep cervical nodes
  • Need to evaluate adjacent structures 1

Step 4: Tissue Sampling (for persistent lymphadenopathy >3 weeks)

• Fine-needle aspiration cytology (FNAC)
  • Initial diagnostic procedure for accessible nodes
  • Can be performed with ultrasound guidance
  • Sensitivity 92.3%, specificity 90.0% for differentiating neoplastic from non-neoplastic 1, 4
• Core needle biopsy
  • Higher diagnostic yield than FNAC
  • Preserves tissue architecture
  • Allows for additional studies (flow cytometry, molecular testing) 1
• Excisional biopsy (gold standard)
  • Indicated when FNAC/core biopsy is non-diagnostic
  • Necessary when lymphoma is strongly suspected
  • Required for complete architectural assessment 1

Special Considerations

For Suspected Infection

• Antibiotics should only be prescribed with evidence of bacterial infection
• Reassess within 2 weeks of treatment
• Further workup for malignancy if mass hasn't completely resolved 1

For Suspected Hematologic Malignancy

• Bone marrow aspiration and biopsy when:
  • Hematologic malignancy is suspected
  • Unexplained cytopenia is present
  • Abnormal cells seen on peripheral blood smear 1

For HIV-Positive Patients

• More thorough evaluation for opportunistic infections
• Higher risk for non-Hodgkin lymphoma
• Consider mycobacterial infections 1

For Suspected HHV-8 Associated Conditions

• Test C-reactive protein
• HHV-8 serum viral load
• Interleukin testing 1, 5

Common Pitfalls to Avoid

1. Delayed Diagnosis: Do not use empiric antibiotics without clear evidence of infection as this may delay diagnosis of malignancy 1

2. Inadequate Follow-up: Even if infectious lymphadenopathy resolves, patients should be reassessed in 2-4 weeks 1

3. Insufficient Sampling: For suspected lymphoma, excisional biopsy is preferred over FNAC to preserve architecture 1, 3

4. Overlooking Systemic Disease: For generalized lymphadenopathy, evaluate for underlying systemic conditions including autoimmune disorders, infections, and malignancies 2, 3

5. Misinterpreting Imaging: In HIV-positive patients, non-malignant causes of lymphadenopathy are more common with higher viral loads and lower CD4+ T-cell counts 5