What is the appropriate evaluation and management for a patient presenting with a swollen lymph node?

Evaluation and Management of Swollen Lymph Nodes

All persistently swollen lymph nodes require tissue diagnosis through biopsy when they persist beyond 4 weeks, exceed 2 cm in size, or demonstrate concerning features such as firm consistency, fixation to surrounding tissues, or supraclavicular/epitrochlear location. 1

Immediate Risk Stratification

High-risk features mandate urgent tissue diagnosis without delay:

• Age >40 years is a mandatory high-risk feature requiring aggressive workup 2
• Size >1.5 cm persisting ≥2 weeks requires tissue diagnosis 2
• Supraclavicular or epitrochlear location carries significantly elevated malignancy risk 1, 2
• Firm, hard, or matted texture with reduced mobility suggests malignancy 2
• Constitutional symptoms (fever, unintentional weight loss >10%, drenching night sweats) suggest lymphoma 1
• Immunocompromised status increases lymphoma and infection risk 2
• Prior malignancy history demands immediate evaluation 2

Essential Clinical Assessment

Document these specific parameters at initial presentation:

• Lymph node characteristics: Measure diameter in two planes, assess consistency (soft vs. firm vs. hard), mobility (mobile vs. fixed), and tenderness 3, 4
• Distribution pattern: Examine all lymph node basins including cervical, supraclavicular (bilateral), axillary, epitrochlear, inguinal, and femoral regions 3, 5
• Duration: Lymphadenopathy persisting >4 weeks requires biopsy 1, 4
• Recent vaccination history: Document COVID-19 vaccination within past 6 weeks, including timing, dose number, and injection site laterality, as vaccine-related adenopathy can persist 4-6 weeks or longer 1

Diagnostic Imaging Algorithm

Follow this stepwise imaging approach based on risk stratification:

Initial Imaging

• Ultrasound is the first-line imaging modality to assess for loss of fatty hilum, round shape, heterogeneous echogenicity, and central necrosis 2
• Ultrasound can guide fine-needle aspiration for tissue diagnosis 2

Advanced Imaging Based on Findings

• CT neck with IV contrast for nodes in difficult anatomical sites or when deep extension assessment is needed 2
• CT chest/abdomen/pelvis is mandatory for nodes ≥5 cm or when staging for confirmed/suspected malignancy 2
• PET-CT is the gold standard for staging FDG-avid lymphomas, with 88% sensitivity and 98% specificity, and valuable for identifying occult primary tumors and guiding biopsy site selection 3, 1, 2
• MRI provides superior soft tissue characterization for nodes overlying difficult anatomical sites such as superior sulcus or brachial plexus involvement 2

Laboratory Evaluation

Obtain these baseline studies before biopsy:

• Complete blood count with differential to assess for atypical lymphocytosis, leukemia, or cytopenias 2
• Lactate dehydrogenase (LDH) levels are associated with lymphoma 2
• HIV testing is necessary, especially in younger patients or those with risk factors, as HIV-positive patients have significantly elevated lymphoma risk 2
• Tuberculosis testing when lymphadenopathy persists beyond four weeks 4
• C-reactive protein and erythrocyte sedimentation rate for inflammatory assessment 4

Tissue Diagnosis Strategy

Excisional biopsy is the gold standard and should not be delayed in high-risk presentations. 1, 2

Biopsy Approach by Clinical Scenario

For suspected lymphoma:

• Excisional or incisional biopsy is preferred to provide adequate tissue for morphology, immunohistochemistry, flow cytometry, and molecular studies 1
• Excisional biopsy preserves nodal architecture necessary for comprehensive pathologic evaluation 1
• Perform microbiological culture when biopsy is done to exclude infectious etiologies 1

For suspected metastatic disease with known primary:

• Fine-needle aspiration (FNA) is preferred as a less invasive initial approach for confirming metastatic disease 2
• Ultrasound-guided FNA should be undertaken if regional lymph nodes are clinically palpable 3
• If FNA results are inconclusive at repeated attempts, proceed to surgical biopsy 3

For nodes in specific anatomical locations:

• Supraclavicular lymphadenopathy: FNA should be the first-line diagnostic test, followed by CT chest/abdomen/pelvis or PET-CT if malignancy confirmed 5
• Core needle biopsy is acceptable but excisional biopsy remains superior for lymphoma diagnosis 1

Immediate Referral Criteria

Refer urgently to hematology-oncology for:

• Nodes >1.5 cm with high-risk features 2
• Hard or matted nodes 2
• Distribution across multiple anatomical regions 2
• B symptoms present (fever, night sweats, weight loss) 2
• Immunosuppression history 2

Refer to ENT/surgical oncology for:

• Suspected head and neck primary malignancy based on symptoms 2
• Need for excisional biopsy 2
• Cervical lymphadenopathy with high-risk features 2

Critical Pitfalls to Avoid

Do not delay biopsy with empiric antibiotics unless bacterial lymphadenitis is clearly suspected, as this can mask malignancy 4

Avoid corticosteroids because they can mask the histologic diagnosis of lymphoma or other malignancy 4

Do not rely solely on FNA for initial lymphoma diagnosis as it may provide insufficient tissue for comprehensive evaluation 1

Do not perform routine surveillance scans after treatment completion, as they lead to false-positive rates, unnecessary investigations, radiation exposure, and patient anxiety 1

Follow-Up Strategy After Treatment

For curable histologies (Hodgkin Lymphoma, DLBCL):

• Every 3 months for the first 2 years 1
• Every 6 months for years 3-5 1
• Annually thereafter 1

Follow-up scans should only be prompted by clinical indications, not performed routinely 1