What is the workup for cervical lymphadenopathy?

Workup for Cervical Lymphadenopathy

The comprehensive workup for cervical lymphadenopathy should include a targeted history, physical examination, laboratory testing, imaging studies, and biopsy when indicated, with specific attention to infectious, malignant, and autoimmune etiologies.

Initial Assessment

History - Key Elements to Assess:

• Duration of lymphadenopathy
• Associated symptoms (fever, night sweats, weight loss)
• Recent infections (viral, bacterial)
• Medication use
• Travel history
• Exposure to animals
• Risk factors for HIV and other infections
• Personal or family history of malignancy
• Smoking history

Physical Examination:

• Characterize lymph nodes:
  • Size (nodes >1.5 cm are concerning)
  • Location (supraclavicular nodes are particularly concerning for malignancy)
  • Consistency (hard, rubbery, soft)
  • Mobility (fixed nodes suggest malignancy)
  • Tenderness (suggests inflammation)
  • Presence of erythema or warmth
• Complete head and neck examination
• Examination of other lymph node regions
• Hepatosplenomegaly assessment

Laboratory Testing

First-line Tests:

• Complete blood count with differential
• Comprehensive metabolic panel
• Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)
• HIV testing
• Hepatitis B and C serologies

Additional Tests Based on Clinical Suspicion:

• EBV serology
• CMV serology
• Toxoplasmosis testing
• Tuberculin skin test or interferon-gamma release assay
• Serum protein electrophoresis
• Lactate dehydrogenase (LDH) and β2-microglobulin (for suspected lymphoma)
• Specific testing for suspected autoimmune disorders

Imaging Studies

Ultrasound:

• First-line imaging modality 1
• Evaluates:
  • Size and morphology of nodes
  • Presence/absence of hilum
  • Vascularity patterns
  • Extracapsular spread

CT Scan with Contrast:

• Indicated when:
  • Malignancy is suspected
  • Need to evaluate extent of disease
  • Assessment of deep cervical nodes
  • Evaluation of adjacent structures

PET-CT:

• Indicated when:
  • Lymphoma is suspected
  • Need to evaluate extent of disease
  • Distinguishing between malignant and non-malignant causes 1

Biopsy

Fine-Needle Aspiration Cytology (FNAC):

• Initial diagnostic procedure for accessible nodes
• May be combined with cell block preparation for improved diagnostic yield 2
• Can be performed with ultrasound guidance

Core Needle Biopsy:

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

Excisional Biopsy:

• Gold standard for diagnosis
• Indicated when:
  • FNAC/core biopsy is non-diagnostic
  • Lymphoma is strongly suspected
  • Need for complete architectural assessment

Special Considerations

HIV-Infected Patients:

• Different spectrum of etiologies compared to HIV-negative patients
• More likely to have mycobacterial infections (38.4% vs 12.5%) 2
• Higher prevalence of opportunistic infections (non-tuberculous mycobacteria, cryptococcosis, Talaromyces marneffei) 2
• Non-Hodgkin lymphoma is the most common malignancy 2
• Infectious disease workup for positive lymph nodes is recommended 3

Persistent Lymphadenopathy:

• Biopsy should be considered after 3 weeks of persistent lymphadenopathy, especially with risk factors for malignancy 4
• Risk factors for malignancy include:
  • Age >40 years
  • Fixed nodes
  • Supraclavicular location
  • Absence of hilum on ultrasound
  • History of malignancy 4

Pediatric Patients:

• Most commonly due to reactive hyperplasia from viral infections 5
• Bacterial infections are the second most common cause
• Malignancy is less common but should not be overlooked

Diagnostic Algorithm

1. Initial evaluation with history, physical examination, and basic laboratory tests
2. Ultrasound as first-line imaging
3. If benign features and low clinical suspicion for malignancy:
   • Observation for 2-4 weeks with or without antibiotics for suspected bacterial infection
4. If persistent, progressive, or concerning features:
   • Advanced imaging (CT or PET-CT)
   • Proceed to biopsy (FNAC → core biopsy → excisional biopsy)
5. Tailor additional testing based on clinical suspicion and initial results

Remember that non-malignant causes of lymphadenopathy are more common in patients with higher viral loads and lower CD4+ T-cell counts in HIV-infected individuals 3. Biopsy should be performed on lesions of uncertain etiology to confirm diagnosis 3.