What is the workup for an enlarged solitary cervical lymph node?

Workup for an Enlarged Solitary Cervical Lymph Node

Begin with a focused history and physical examination to stratify malignancy risk, then proceed directly to imaging (ultrasound or CT) and excisional biopsy for nodes >1.5 cm, firm texture, reduced mobility, or duration >2 weeks without infectious etiology. 1

Initial Risk Stratification Through History

High-risk historical features that mandate aggressive workup include: 1

• Age >40 years (traditional head and neck squamous cell carcinoma risk) 1
• Tobacco use and alcohol abuse 1
• HPV-related risk factors: increased number of sexual partners and oral sex exposure (note: HPV-positive oropharyngeal cancer may occur without traditional risk factors) 1
• Immunocompromised status (HIV, organ transplant, immunosuppressive medications) 1, 2
• Concerning symptoms: hoarseness, otalgia, hearing loss, intraoral swelling/ulceration, new oral numbness, dyspnea, odynophagia, dysphagia, weight loss, hemoptysis, nasal congestion, unilateral epistaxis 1
• B symptoms (fever, night sweats, weight loss) suggest lymphoma and require expedited referral with PET-CT 2, 3
• Prior head and neck malignancy including skin cancer of scalp, face, or neck 1

Physical Examination Findings That Indicate Malignancy

Suspicious nodal characteristics requiring immediate workup: 1

• Size >1.5 cm in any cervical location (jugulodigastric nodes up to 1.5 cm may be normal) 1
• Firm or hard texture (though HPV-positive head and neck cancer can present with soft, cystic masses) 1
• Reduced mobility in longitudinal or transverse planes 1
• Ulceration of overlying skin 1
• Multiple, grouped, or matted lymph nodes 1
• Continued increase in size 1
• Duration ≥2 weeks without infectious etiology 1, 4
• Supraclavicular location (always abnormal and highly concerning for malignancy) 4, 5

Diagnostic Imaging

For any node meeting high-risk criteria, obtain imaging before or concurrent with biopsy: 1, 2

• CT neck with IV contrast to evaluate deep extension, though it has limited soft tissue characterization (43-55% sensitivity for parametrial invasion in cervical cancer studies) 1
• Ultrasound can assess for loss of fatty hilum, round shape (versus oval), heterogeneous echogenicity, and central necrosis—all concerning features 3
• Chest radiograph to evaluate for synchronous bronchial tumors or mediastinal involvement 1
• PET-CT if B symptoms present or lymphoma suspected 2

Laboratory Evaluation

Obtain these studies before or concurrent with specialist referral: 2

• Complete blood count with differential (assess for atypical lymphocytosis, leukemia, cytopenias) 2, 6
• Comprehensive metabolic panel including LDH 2
• β2-microglobulin 2
• HIV testing (especially in younger patients or those with risk factors) 1, 2
• Serum soluble IL-2 receptor (useful adjunct in determining biopsy necessity) 7

Biopsy Strategy

Excisional biopsy is the gold standard for definitive diagnosis and should not be delayed in high-risk presentations: 2, 7, 5

• Excisional biopsy preserves nodal architecture necessary for accurate lymphoma classification and is superior to fine-needle aspiration 2, 7
• Fresh tissue must be sent in saline (not formalin) for flow cytometry, immunohistochemistry, and molecular studies 2, 6
• Core needle biopsy or fine-needle aspiration may be considered for initial evaluation but often require subsequent excisional biopsy for definitive diagnosis 5

Observation Period (Low-Risk Cases Only)

A 2-4 week observation period is acceptable ONLY for: 4, 5

• Nodes <1.5 cm with soft texture and mobile consistency 1, 4
• Clear infectious etiology present 4
• No high-risk historical features 1
• Age <40 years without other risk factors 1, 4

However, 38% of persistently enlarged cervical nodes prove malignant (61 metastatic disease, 62 lymphoma in one series), so threshold for biopsy should be low. 8

Referral Pathways

Immediate hematology-oncology referral for: 2

• Nodes >1.5 cm in long axis or >1.0 cm in short axis 2
• Hard or matted nodes 2
• Distribution across multiple anatomical regions 2
• B symptoms present 2
• Immunosuppression history 2

ENT/surgical oncology referral for: 1

• Suspected head and neck primary malignancy based on symptoms (hoarseness, dysphagia, otalgia) 1
• Need for excisional biopsy 2

Critical Pitfalls to Avoid

• Do not empirically treat with antibiotics without clear infectious etiology—this delays diagnosis of malignancy 5
• Do not use corticosteroids without appropriate diagnosis—they have limited usefulness and may obscure lymphoma 5
• Do not rely on size alone—normal-sized nodes can harbor microscopic metastases, and enlarged nodes may be hyperplastic 3
• Do not send tissue in formalin if lymphoma suspected—fresh tissue in saline is required for flow cytometry 2, 6
• Supraclavicular nodes are always abnormal—immediate workup required regardless of other features 4, 5

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