What is the recommended evaluation and management for a patient with enlarged lymph nodes?

Evaluation and Management of Enlarged Lymph Nodes

For adults with painless lymph node enlargement, immediately assess for high-risk features (age >40, size >1.5 cm, firm/hard texture, reduced mobility) and proceed directly to tissue diagnosis via excisional biopsy or ultrasound-guided FNA; in children, lymph nodes ≤15 mm with benign features require no further workup, while nodes >15 mm or lacking a fatty hilum warrant ultrasound evaluation and consideration of excisional biopsy. 1, 2

Initial Risk Stratification

Adults

• Age >40 years is a mandatory high-risk feature requiring aggressive workup 2
• Nodes >1.5 cm persisting ≥2 weeks require tissue diagnosis 2
• Firm/hard texture, reduced mobility, and non-tender character are concerning for malignancy 2
• Supraclavicular location is particularly worrisome and should prompt immediate evaluation 3
• Additional risk factors include tobacco use, alcohol abuse, HPV exposure, prior head/neck malignancy, and immunocompromised status 2

Children

• Lymph nodes ≤15 mm in short axis are consistently benign and require no further workup 1
• Nodes >15 mm warrant further evaluation for potential malignancy 1
• Nodes with fatty hilum and oval shape are benign and require no imaging follow-up or biopsy 1
• Red flags include round (not oval) shape, loss of fatty hilum, irregular borders, necrosis, or extranodal extension 1

Clinical Assessment

Document the following specific features during examination:

• Duration and pattern of enlargement 1
• Size, number, and anatomical location of all enlarged nodes 1
• B symptoms (fever >38.3°C, night sweats, weight loss) suggest lymphoma and require PET/CT imaging 4, 1
• History of immunosuppression 1
• Presence of hepatosplenomegaly 5
• For children aged 1-5 years with cervical adenopathy, consider nontuberculous mycobacterial (NTM) infection, particularly Mycobacterium avium complex 1, 2

Diagnostic Imaging Algorithm

First-Line Imaging

• Ultrasound is the initial imaging modality of choice for accessible lymph nodes 1, 2
• Assess for loss of fatty hilum, round shape, heterogeneous echogenicity, and central necrosis 2
• Ultrasound can guide FNA for tissue diagnosis with 93% sensitivity and 91% specificity 2, 5

Advanced Imaging

• 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
• MRI provides superior soft tissue characterization for nodes overlying difficult anatomical sites (superior sulcus, brachial plexus involvement) 2, 5
• PET-CT is most valuable for lymphoma staging (88% sensitivity, 98% specificity), identifying occult primary tumors, and guiding biopsy site selection 4, 2, 5

Essential Laboratory Evaluation

• Complete blood count with differential to assess for atypical lymphocytosis, leukemia, or cytopenias 2, 5
• Lactate dehydrogenase (LDH) levels are associated with lymphoma 2, 5
• HIV testing is necessary, especially in younger patients or those with risk factors 2
• Blood chemistry including routine parameters 5
• Flow cytometry for suspected hematologic malignancies 5

Tissue Diagnosis Strategy

Excisional Biopsy (Gold Standard)

• All nodes >1.5 cm persisting ≥2 weeks require tissue diagnosis 2
• Excisional biopsy should not be delayed in high-risk presentations 2
• Provides entire lymph node for comprehensive histological analysis, essential for lymphoma diagnosis 4, 5, 6
• Surgical biopsy significantly reduces investigation time (1.25 months vs. 3 months with needle biopsy first) 7

Fine-Needle Aspiration

• Less invasive initial approach for confirming metastatic disease when primary malignancy is known 2
• Sensitivity of 93% and specificity of 91% for palpable nodes 5
• For lymphoma diagnosis, sensitivity is only 67-68% and specificity 71-79%, making excisional biopsy preferable 7
• If FNA is non-diagnostic or lymphoma is suspected, proceed to excisional biopsy 5

Observation vs. Immediate Workup

Safe to Observe (2-4 weeks)

• Children: nodes ≤15 mm with benign features (fatty hilum, oval shape) 1
• Adults: localized cervical lymphadenopathy with benign clinical picture, no high-risk features 3
• Nodes <1 cm in diameter (generally considered normal) 3

Requires Immediate Investigation

• Any node >1.5 cm in adults 2
• Any node >15 mm in children 1
• Presence of B symptoms 4, 1
• Progressive enlargement on subsequent imaging 1
• Generalized lymphadenopathy 3, 6
• Supraclavicular location 3
• Rock hard, rubbery, or fixed consistency 3

Referral Pathways

Hematology-Oncology Referral

Immediate referral indicated for:

• Nodes >1.5 cm 2
• Hard or matted nodes 2
• Distribution across multiple anatomical regions 2
• B symptoms present 2
• Immunosuppression history 2

ENT/Surgical Oncology Referral

Indicated for:

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

Special Clinical Scenarios

• NTM lymphadenitis in children: Excisional surgery without chemotherapy is the treatment of choice with 95% success rate 2
• Sjögren's syndrome patients: Lymphoma risk ranges from 5-18% 2
• CLL patients on lenalidomide: Tumor flare reactions occur in 50-90% of cases 2
• Epidermolysis bullosa patients: Enlarged nodes often secondary to inflammation/infection, but metastatic squamous cell carcinoma must be excluded 2

Common Pitfalls to Avoid

• Do not rely on size alone: Normal-sized nodes can harbor microscopic disease, and enlarged nodes may be hyperplastic 1, 5
• Do not assume all enlarged nodes are infectious: While most are benign, systematic evaluation prevents missed malignancies 1
• Do not perform unnecessary biopsies on nodes with fatty hilum and benign morphology in children, which have extremely low malignancy risk 1
• Do not delay excisional biopsy when lymphoma is suspected, as needle biopsy has inadequate sensitivity 7
• Do not forget bone marrow biopsy is no longer routinely indicated for staging of Hodgkin lymphoma and most diffuse large B-cell lymphomas 4