What tests are ordered for a patient presenting with cervical lymphadenopathy (cervical lymph node enlargement)?

Diagnostic Testing for Cervical Lymphadenopathy

For a patient presenting with cervical lymphadenopathy, order contrast-enhanced CT or MRI of the neck as the primary imaging study if malignancy risk is elevated, along with complete blood count with differential, and consider ultrasound as the initial imaging modality for lower-risk presentations. 1, 2, 3

Initial Risk Stratification

Before ordering tests, assess key features that determine malignancy risk:

• Duration ≥2 weeks without improvement is concerning for malignancy 2, 3
• High-risk node characteristics include: size >1.5 cm, firm or rock-hard consistency, fixed/immobile nodes, supraclavicular location, and ulceration of overlying skin 1, 2, 3, 4
• Systemic "B symptoms" (fever, night sweats, unexplained weight loss) suggest lymphoma or advanced malignancy 2, 3
• Posterior cervical chain involvement is particularly concerning for lymphoma, nasopharyngeal carcinoma, metastatic head and neck tumors, or tuberculosis 2

Laboratory Testing

Essential Initial Tests

• Complete blood count (CBC) with differential to evaluate for cytopenias, abnormal cell populations, lymphocytosis, or eosinophilia 2, 3, 5, 6
• Peripheral blood smear review if CBC shows abnormalities suggestive of hematologic malignancy 5
• Inflammatory markers (ESR, CRP) when infectious or inflammatory etiology is suspected 3, 6

Additional Tests Based on Clinical Suspicion

• Tuberculin skin test (PPD) or interferon-gamma release assay if granulomatous disease or mycobacterial infection is suspected 2, 5, 6
• HIV testing if risk factors are present or lymphadenopathy is unexplained 3, 5
• Viral studies (EBV, CMV) when infectious mononucleosis or viral etiology is suspected 5, 6
• Monospot test for suspected infectious mononucleosis 6
• Toxoplasmosis serology (indirect fluorescent antibody test) when clinically indicated 6
• Lactate dehydrogenase (LDH) as a marker for hemolysis or malignancy 5

Imaging Studies

First-Line Imaging

Ultrasound of the neck is the recommended initial imaging study for most presentations 2, 3, 5. Ultrasound can assess:

• Node size, morphology, and vascularity 3
• Presence of necrosis 3
• Hypoechoic core suggesting bacterial infection 3

Advanced Imaging for High-Risk Patients

Contrast-enhanced CT or MRI of the neck should be ordered for patients at increased risk for malignancy 1, 2. The American Academy of Otolaryngology-Head and Neck Surgery provides strong recommendation (Level IV evidence) for this approach 1. These modalities:

• Define extent of disease and facilitate staging 1
• Detect occult disease 1
• Guide treatment decisions and referral 1

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

FDG-PET/CT is standard of care for metastatic cervical adenopathy with no primary evident on clinical examination, with 69% detection rate for occult primary tumors 1

Tissue Sampling

When to Obtain Tissue

Indications for biopsy include:

• Persistence beyond 4-6 weeks without diagnosis 3
• Size >2 cm without improvement 3
• Presence of suspicious features (firm, fixed, supraclavicular location) 3
• Lymphadenopathy persisting ≥2 weeks without significant fluctuation or failing to resolve after antibiotics 2

Biopsy Approach

• Fine-needle aspiration (FNA) is preferred over open biopsy for initial tissue sampling, with diagnostic accuracy of 96% reported 2
• Excisional biopsy should be considered when FNA is non-diagnostic or inconclusive, or when lymphoma is suspected 2
• For lymphoma evaluation, tissue should be sent for immunohistochemistry and flow cytometry 1, 5

Critical Pitfalls to Avoid

• Do not give empiric antibiotics without evidence of infection, as they may delay diagnosis of malignancy 3
• Do not dismiss persistent cervical lymphadenopathy without proper evaluation, especially if duration exceeds 2 months 3
• Do not rely on imaging alone—physical examination by an otolaryngologist with visualization of the larynx, base of tongue, and pharynx is essential for posterior cervical or high-risk presentations 2
• Do not delay bone marrow evaluation in patients with concerning peripheral blood findings 5

Referral Timing

Prompt referral to an otolaryngologist is indicated if lymphadenopathy persists ≥2 weeks without significant fluctuation or fails to resolve after antibiotics 2. For patients with high-risk features (supraclavicular nodes, firm/fixed consistency, B symptoms), referral should be immediate rather than waiting for the 2-week threshold 1, 2.