What is the diagnostic workup for generalized lymphadenopathy?

Diagnostic Workup for Generalized Lymphadenopathy

A risk-stratified approach is recommended for generalized lymphadenopathy workup, starting with thorough history, physical examination, basic laboratory tests, and ultrasound as first-line imaging, proceeding to tissue sampling for persistent or concerning lymphadenopathy. 1

Initial Evaluation

History - Key Elements

• Duration of lymphadenopathy
• Associated symptoms (fever, night sweats, weight loss)
• Recent infections or dental problems
• Medication use
• Risk factors for HIV and hepatitis
• Travel history
• Age (patients >40 years have increased malignancy risk) 1, 2

Physical Examination

• Document location, size, consistency, and mobility of nodes
• Assess for hepatosplenomegaly
• Note abnormal nodes:
  • Supraclavicular nodes (always abnormal)
  • Popliteal and iliac nodes (always abnormal)
  • Epitrochlear nodes >5 mm (abnormal) 1, 2

Laboratory Evaluation

The initial laboratory workup should include:

Test	Purpose
Complete blood count with differential	Evaluate for anemia, leukocytosis, thrombocytopenia
Erythrocyte sedimentation rate (ESR)	Assess inflammation
Serum lactate dehydrogenase (LDH)	Evaluate tissue damage
Comprehensive metabolic panel	Assess liver and renal function
Hepatitis B testing (HBsAg and HBcAb)	Rule out hepatitis B
Hepatitis C testing (in high-risk patients)	Rule out hepatitis C
HIV testing	Rule out HIV infection [1]

Imaging Studies

• First-line: Ultrasound of affected nodal regions

  • Assesses size, morphology, hilum presence/absence, vascularity patterns 1

• Second-line: CT chest/abdomen/pelvis with contrast

  • Indicated when malignancy is suspected
  • Evaluates extent of disease, deep nodes, and adjacent structures 1

• Advanced imaging: PET-CT

  • Consider when lymphoma is suspected 1

Tissue Sampling

Tissue sampling is critical for definitive diagnosis when lymphadenopathy persists beyond 1 month or when malignancy is suspected:

1. Fine-needle aspiration cytology (FNAC)

   • Less invasive but limited sample
   • Sensitivity: 92.3%, Specificity: 90.0% for differentiating neoplastic from non-neoplastic lymphadenopathy 1

2. Core needle biopsy

   • Higher diagnostic yield than FNAC
   • Preserves tissue architecture
   • Allows for additional studies (flow cytometry, molecular testing) 1

3. Excisional biopsy

   • Gold standard for lymphoma diagnosis
   • Required for accurate classification of lymphoma subtypes 1, 3

Special Considerations

Risk Factors for Malignancy

• Age >40 years
• Male sex
• White race
• Supraclavicular location
• Systemic symptoms (fever, night sweats, unexplained weight loss) 2

Bone Marrow Evaluation

• Indicated when:
  • Hematologic malignancy is suspected
  • Unexplained cytopenia is present
  • Abnormal cells are seen on peripheral blood smear 1

Autoimmune Considerations

• Consider autoimmune disorders like systemic lupus erythematosus (SLE) in patients with generalized lymphadenopathy and constitutional symptoms, especially with neurological symptoms 4

Infectious Disease Evaluation

• HIV, toxoplasmosis, secondary syphilis, and tuberculosis are common infectious causes of generalized lymphadenopathy 5
• HIV patients have higher prevalence of opportunistic infections and non-Hodgkin lymphoma 1

Common Pitfalls to Avoid

1. Inappropriate antibiotic use

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

2. Delayed diagnosis

   • Empiric antibiotics without indication may delay diagnosis of malignancy
   • Persistent cervical lymphadenopathy >3 weeks despite antibiotics warrants biopsy 1

3. Corticosteroid use

   • Limited usefulness in unexplained lymphadenopathy
   • Should not be used without appropriate diagnosis 2

4. Inadequate biopsy

   • Excision of entire lymph nodes is essential for lymphoma diagnosis 3