What is the initial workup for a patient with chronic cervical lymphadenopathy?

Workup for Chronic Cervical Lymphadenopathy

Patients with persistent cervical lymphadenopathy for ≥2 weeks without significant fluctuation should be referred to an otolaryngologist for prompt specialist evaluation, as this duration is concerning for malignancy. 1

Initial Primary Care Assessment

Physical Examination - Key Features to Document

• Node characteristics: Size (>1.5 cm raises malignancy concern), consistency (firm nodes suggest malignancy), mobility (fixation to adjacent tissues indicates malignancy), and overlying skin changes (ulceration is concerning) 1, 2
• Location: Supraclavicular, popliteal, iliac, and epitrochlear nodes >5 mm are abnormal and warrant urgent evaluation 3
• Posterior cervical chain involvement is particularly concerning for lymphoma, nasopharyngeal carcinoma, metastatic head/neck tumors, or tuberculosis 2
• Systemic symptoms: Fever, night sweats, weight loss (B symptoms suggesting lymphoma or infection) 1, 2
• All node-bearing areas: Cervical, supraclavicular, axillary, inguinal regions, plus hepatosplenomegaly 4

Initial Laboratory Testing

• Complete blood count with differential 2, 3
• Comprehensive metabolic panel including renal and liver function 4
• Lactate dehydrogenase (LDH) - critical prognostic marker for lymphoma 4, 5
• Erythrocyte sedimentation rate 4
• Serum protein electrophoresis and immunoglobulin levels 4, 5
• β2-microglobulin - prognostic marker for hematologic malignancies 4, 5
• Hepatitis B, C, and HIV serology (required before immunotherapy/chemotherapy) 4
• Tuberculin skin test (PPD) if mycobacterial infection suspected 2

First-Line Imaging

Ultrasound of the neck is the recommended first-line imaging study 2, though even benign ultrasound findings require continued evaluation until definitive diagnosis is obtained 1

• Chest X-ray to assess for pulmonary involvement or hilar lymphadenopathy 2

Specialist Evaluation by Otolaryngologist

When to Refer Urgently

• Lymphadenopathy persisting ≥2 weeks 1
• Failure to resolve after antibiotic course (partial resolution may represent infection in underlying malignancy) 1
• Firm, fixed nodes >1.5 cm 1
• Presence of B symptoms 1
• Supraclavicular or posterior cervical location 2, 3

Specialist Diagnostic Approach

The otolaryngologist should perform targeted physical examination including direct visualization of the larynx mucosa, base of tongue, and pharynx 1, 2 - this is critical as posterior cervical nodes may represent metastatic head/neck primary tumors.

Advanced Imaging

Cross-sectional imaging with contrast-enhanced CT or MRI is strongly recommended for patients at increased risk for malignancy 1, 2

• CT chest/abdomen/pelvis with oral and IV contrast if systemic disease suspected 1
• PET-CT valuable for evaluation of suspicious findings on other imaging modalities 1
• CT neck with contrast to characterize lymphadenopathy and identify occult primary tumors 2

Tissue Sampling Strategy

Fine-needle aspiration (FNA) is preferred over open biopsy for initial tissue sampling 1, 2, with diagnostic accuracy of 96% reported 2

• Excisional biopsy should be performed when FNA is non-diagnostic/inconclusive or when lymphoma is suspected 2
• Never assume a cystic neck mass is benign without obtaining definitive diagnosis - this can delay malignancy diagnosis 1
• Core biopsies should only be used when easily accessible nodes are unavailable 4

Specialized Testing on Tissue

• Immunophenotyping is essential for differentiating lymphoma subtypes 1
• Flow cytometry panel should include CD19, CD20, CD5, CD10, CD11c, CD22, CD25, CD103, CD123, cyclin D1, CD200 4
• Cytogenetic/molecular genetic analysis (FISH) to identify chromosomal translocations 1
• Bone marrow aspirate and biopsy (≥20 mm size) if lymphoma or leukemia suspected 4

Critical Pitfalls to Avoid

Never prescribe additional antibiotics without signs of bacterial infection - this delays malignancy diagnosis 1. Cervical lymphadenopathy that fails to resolve after antibiotics warrants immediate specialist referral 1.

Avoid empiric antitubercular treatment without microbiological/histopathological confirmation - tuberculosis can mimic lymphoma, drug-resistant TB, and other etiologies, leading to treatment failure 6

Differential Diagnosis Context

In developing countries, tuberculosis accounts for 25% of chronic cervical lymphadenopathy in children 7, while in Western populations, reactive lymphoid hyperplasia is most common (47.8%) 7. Malignancy represents 1.5-2.1% of cases but must be excluded 7, 8. Risk factors for malignancy include age >40 years, male sex, white race, supraclavicular location, and systemic symptoms 3.

Follow-Up Strategy

• If initial workup is inconclusive but clinical suspicion remains, repeat imaging in 3 months 1
• Persistent lymphadenopathy requires definitive diagnosis through tissue sampling if initial workup is inconclusive 1
• For diagnosed malignancy: follow-up every 1-3 months (year 1), every 2-6 months (year 2), every 4-8 months (years 3-5), then annually 1