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

Workup of Enlarged Cervical Lymph Node

The initial workup requires immediate risk stratification through history and physical examination, followed by imaging and tissue diagnosis—with excisional biopsy as the gold standard for definitive diagnosis in high-risk presentations. 1

Risk Stratification Through History

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

• Age >40 years 1
• Tobacco use and alcohol abuse 1
• HPV-related risk factors 1
• Immunocompromised status (HIV, organ transplantation, immunosuppressive therapy) 1, 2
• Prior head and neck malignancy, including skin cancer of the scalp, face, or neck 1

Assess for B symptoms systematically: 3, 2

• Recurrent unexplained fever >38°C 3
• Recurrent night sweats 3
• Unintentional weight loss 3

The presence of B symptoms strongly suggests lymphoma and necessitates expedited referral with PET-CT imaging. 2

Physical Examination Findings

Suspicious nodal characteristics requiring immediate workup include: 1

• Size >1.5 cm in long axis (or >1.0 cm in short axis) 1, 2
• Firm or hard texture 1
• Reduced mobility or fixed consistency 1, 4
• Ulceration of overlying skin 1
• Multiple or matted lymph nodes 1, 2
• Continued increase in size 1
• Supraclavicular location (particularly high-risk for malignancy) 4

Nodes larger than 1 cm in diameter are generally considered abnormal. 4 Rock hard, rubbery, or fixed consistency should raise concern for malignancy. 4

Examine other nodal regions to exclude generalized lymphadenopathy and check for hepatosplenomegaly. 5

Laboratory Evaluation

Obtain the following laboratory studies before or concurrent with referral: 2

• Complete blood count with differential to assess for atypical lymphocytosis, leukemia, or cytopenias 5, 2
• Comprehensive metabolic panel including LDH 2
• β2-microglobulin 2
• Erythrocyte sedimentation rate 3
• Serum albumin 3
• HIV testing, especially in younger patients or those with risk factors 1, 2
• HBV, HCV testing 3
• Tuberculosis testing with PPD or interferon-gamma release assay if the node is unilateral and non-tender 5

Diagnostic Imaging

CT neck with IV contrast evaluates deep extension and is recommended for comprehensive assessment. 1, 2 For suspected lymphoma, CT chest/abdomen/pelvis provides comprehensive nodal and extranodal assessment. 2

Ultrasound can assess for concerning features including loss of fatty hilum, round shape, heterogeneous echogenicity, and central necrosis. 1

Chest radiograph evaluates for synchronous bronchial tumors or mediastinal involvement. 1

Baseline FDG-PET scan is strongly recommended (though not mandatory) before initiation of therapy in suspected lymphoma cases. 3

Tissue Diagnosis Strategy

Excisional biopsy is the gold standard for definitive diagnosis and should not be delayed in high-risk presentations. 1, 2 This approach preserves nodal architecture necessary for accurate lymphoma classification. 2

Indications for excisional biopsy include: 1, 5

• Nodes >1.5 cm 1
• Hard or matted nodes 1
• Supraclavicular location 5
• Node >2 cm persisting >4-6 weeks 5
• Absence of infectious symptoms 5
• Concerning imaging features 5

Critical technical consideration: Fresh tissue should be sent in saline (not formalin) for flow cytometry, immunohistochemistry (CD20, CD10, Ki-67), and cytogenetics. 5, 2

Fine needle aspiration with panendoscopy should be the first-line diagnostic approach when malignancy is suspected but the primary site is unknown. 6 However, excisional biopsy remains superior for lymphoma diagnosis. 2

Observation Period for Low-Risk Presentations

Patients with unexplained localized cervical lymphadenopathy presenting with a benign clinical picture (no high-risk features, soft consistency, mobile, <1.5 cm) should be observed for a 2- to 4-week period. 4 Persistently swollen nodes after this period should trigger biopsy. 7

Referral Pathways

Immediate hematology-oncology referral is necessary for: 1, 2

• Nodes >1.5 cm 1
• Hard or matted nodes 1
• Distribution across multiple anatomical regions 1
• B symptoms present 1
• Immunosuppression history 1

ENT/surgical oncology referral is necessary for: 1

• Suspected head and neck primary malignancy based on symptoms 1
• Need for excisional biopsy 1

Critical Pitfalls to Avoid

Do not perform incisional biopsy or adenectomy as initial diagnostic approach in suspected malignancy, as this significantly increases neck failure rates (54% vs. 15% with fine needle aspiration followed by appropriate definitive surgery). 6

Do not delay biopsy in high-risk presentations. In a large series, 38% of persistently swollen cervical lymph nodes were malignant (metastatic disease or lymphoma), with patients ranging from 15 to 92 years old. 7

Generalized lymphadenopathy (involvement of multiple non-contiguous nodal regions) should prompt immediate further clinical investigation rather than observation. 4