What is the recommended evaluation and management for lymphadenopathy?

Evaluation and Management of Lymphadenopathy

Any lymphadenopathy persisting beyond 2 weeks requires systematic investigation, with nodes ≥1.5 cm significantly increasing the risk for malignancy or chronic infection and warranting tissue diagnosis if they fail to resolve. 1, 2

Initial Clinical Assessment

History Taking Priorities

• Duration of lymphadenopathy is critical—persistence beyond 2 weeks is suspicious and demands further workup 1, 2, 3
• B-symptoms (fever >38°C, night sweats, weight loss >10% in 6 months) strongly suggest malignancy 1, 3
• Recent infections (respiratory, dental problems), animal exposures, and travel history help identify infectious etiologies 1, 4, 3
• Family history of lymphoproliferative disorders or tuberculosis exposure is essential for risk stratification 1
• Medication history and recent vaccinations may explain reactive adenopathy 3

Physical Examination Characteristics

• Distinguish localized versus generalized lymphadenopathy (involvement of ≥2 non-contiguous regions suggests systemic disease) 3, 5
• Size matters: nodes >1.5-2 cm are concerning, particularly if >2 cm without improvement 1, 4, 5
• Texture and mobility: hard, fixed, matted, or ulcerated nodes are highly suspicious for malignancy 4, 3, 5
• Location-specific risk: supraclavicular, epitrochlear (>5 mm), popliteal, and iliac nodes are abnormal and warrant immediate investigation 4, 5

Laboratory Evaluation

Order these tests systematically:

• Complete blood count with differential to rule out hematologic malignancy 1, 3
• Inflammatory markers (ESR, CRP) assess severity of infection or inflammation 1, 4
• LDH, albumin, liver and kidney function provide prognostic information and assess systemic involvement 1
• Tuberculin skin test (PPD) is mandatory before biopsy to differentiate tuberculosis from non-tuberculous mycobacteria (NTM)—critical for treatment decisions and public health reporting 1
• HIV testing if risk factors present 4, 3

Imaging Strategy

Follow this algorithmic approach:

1. Ultrasound is first-line for all peripheral lymphadenopathy to assess size, morphology, vascularity, and cortical thickness 1, 4

   • Cortical thickness >3 mm is suspicious; >7 mm strongly correlates with metastatic disease 1, 4

2. Chest X-ray to rule out intrathoracic lymphadenopathy or tuberculosis 1

3. CT scan of neck, thorax, abdomen, and pelvis for nodes ≥5 cm or in difficult anatomical locations to assess extent and involvement of underlying structures 1, 4

4. For suspected lymphoma: PET-CT is the gold standard for staging FDG-avid lymphomas (all histologies except CLL/SLL, lymphoplasmacytic lymphoma, mycosis fungoides, and marginal zone NHL) 6

   • Contrast-enhanced CT should be included for accurate nodal measurement and to distinguish bowel from lymphadenopathy 6

Tissue Diagnosis: When and How

Indications for Biopsy

Proceed directly to biopsy if:

• Lymphadenopathy persists >2 weeks without clear infectious etiology 1, 2
• Nodes ≥1.5 cm with suspicious features (hard, fixed, matted) 1, 4
• Cortical thickness >7 mm on ultrasound 1, 4
• Supraclavicular, epitrochlear, or other high-risk locations 4, 5
• Any B-symptoms present 1, 3

Biopsy Technique Selection

Use this hierarchy:

1. Excisional biopsy is the gold standard for suspected lymphoma or when core biopsy is inconclusive—provides complete tissue architecture for histopathology, immunophenotyping, cytogenetics, and culture 1, 4, 2

2. Ultrasound-guided core needle biopsy is superior to fine-needle aspiration (sensitivity 88% vs. 74%) and should be the preferred initial approach when excisional biopsy is not immediately feasible 1, 4, 2

3. Fine-needle aspiration alone is insufficient—it may miss focal pathology in heterogeneous lesions and provides inadequate tissue for comprehensive diagnosis 1, 4

Critical pitfall: For lymphoma evaluation, bone marrow biopsy is no longer indicated for routine staging of Hodgkin lymphoma or most diffuse large B-cell lymphomas if PET-CT is performed 6

Management Based on Clinical Scenario

If Acute Bacterial Infection Suspected

• Start empirical antibiotics only if signs of acute bacterial infection present: rapid onset, fever, tenderness, overlying erythema 1, 3
• Follow-up within 2 weeks to assess resolution, progression, or persistence 1

If Lymphadenopathy Persists Without Acute Infection

• Do NOT give empirical antibiotics without signs of acute bacterial infection—this delays diagnosis of malignancy or chronic infection 1, 4
• Proceed directly to imaging and biopsy as outlined above 1, 4

Special Population: Pediatric NTM Lymphadenitis

• Consider in children age 1-5 years with unilateral cervical adenopathy (95% unilateral, ~80% due to Mycobacterium avium complex) 1
• Complete surgical excision without chemotherapy is treatment of choice with ~95% success rate 1, 4
• For large nodes (≥5 cm) or difficult locations: clarithromycin multidrug regimen with corticosteroids may be considered 1

Kawasaki Disease Consideration

• Cervical lymphadenopathy ≥1.5 cm should prompt consideration of Kawasaki disease, even if other main criteria initially absent 1

Lymphoma-Specific Staging (When Diagnosed)

For FDG-avid lymphomas:

• PET-CT defines involvement: focal uptake in nodal and extranodal sites consistent with lymphoma distribution indicates disease 6
• Measurable nodes must have longest diameter >1.5 cm; measurable extranodal lesions >1.0 cm 6
• Bulky disease definition: single nodal mass ≥10 cm or greater than one-third transthoracic diameter for Hodgkin lymphoma 6

Critical caveat: Avoid corticosteroids before tissue diagnosis—they can mask histologic diagnosis of lymphoma or other malignancy 3, 5