What is the appropriate workup for an adult patient with no significant past medical history presenting with a neck lymph node?

Workup of Neck Lymph Node in Adults

For any adult presenting with a neck lymph node, immediately assess for high-risk features that mandate urgent malignancy workup: lymph node present ≥2 weeks without infectious cause, size >1.5 cm, firm consistency, fixation to adjacent tissues, or ulceration of overlying skin—if any are present, proceed directly to contrast-enhanced CT imaging and fine-needle aspiration rather than observation. 1, 2

Initial Risk Stratification

High-Risk Features Requiring Immediate Workup

History-based red flags:

• Lymph node present ≥2 weeks without infectious etiology or of uncertain duration 1
• Age >40 years (dramatically increases malignancy risk, especially for cystic masses where 80% are malignant) 1
• Tobacco and alcohol use (synergistic risk factors for head and neck squamous cell carcinoma) 1
• Constitutional B symptoms: unexplained weight loss, fever, drenching night sweats 1, 2
• Pharyngitis, dysphagia, otalgia, voice change, or nasal obstruction ipsilateral to the mass 1

Physical examination red flags:

• Size >1.5 cm (lymph node metastases cause nodal enlargement) 1
• Firm or hard consistency (malignant nodes lack tissue edema) 1
• Fixation to adjacent tissues (suggests capsular invasion) 1
• Ulceration of overlying skin (indicates direct invasion) 1
• Supraclavicular location (high malignancy association) 3

Lower-Risk Features

• Recent documented infection with fluctuating node size 1
• Soft, mobile, tender lymph node <1.5 cm 1
• Clear infectious symptoms present 1

Critical caveat: Soft texture does NOT exclude malignancy—cystic metastases from HPV-positive oropharyngeal cancer commonly present as soft masses, and up to 62% of metastases from Waldeyer ring sites are cystic 1, 4

Mandatory Imaging for High-Risk Patients

Order contrast-enhanced CT of the neck (or MRI with contrast if CT contraindicated) immediately for any patient meeting high-risk criteria. 1, 2

Imaging objectives:

• Assess internal characteristics (solid vs. cystic, necrosis, enhancement patterns) 2
• Identify additional pathologic lymph nodes in other cervical levels 2
• Evaluate for primary tumor sites in the upper aerodigestive tract 2
• Determine fixation to adjacent structures 4
• Assess for mediastinal or abdominal involvement suggesting lymphoma 2

Extend imaging to include chest and abdomen if:

• Multiple enlarged nodes are present 2
• Constitutional symptoms suggest systemic disease 2
• Initial neck imaging shows suspicious features 2

Consider PET-CT when:

• Initial CT shows suspicious findings requiring staging 2
• Lymphoma is suspected based on clinical/imaging features 1, 2
• Newly enlarging nodes without definite morphologic abnormalities on CT alone 4

Targeted Physical Examination

Perform or refer for direct visualization of the larynx, base of tongue, and pharynx using laryngoscopy to identify occult primary tumors in the upper aerodigestive tract. 1, 2

This examination is mandatory because head and neck squamous cell carcinomas commonly metastasize to cervical lymph nodes before the primary tumor becomes symptomatic, and up to 10% of malignant cystic neck masses present without an obvious primary tumor on routine examination 1

Tissue Diagnosis Strategy

Perform fine-needle aspiration (FNA) as the initial tissue sampling method—NOT open biopsy. 1, 2

FNA advantages:

• Minimally invasive with no complications in large series 5
• Establishes diagnosis in approximately 98% of cases when adequate 6
• Provides sufficient tissue for immunophenotyping and molecular studies in 94% of cases 5

FNA technique considerations:

• Use image-guided FNA (ultrasound or CT) to target solid components or cyst wall if cystic features are present 1, 2
• Ensure adequate tissue collection for routine histology, immunophenotyping, and potential molecular studies 2
• Sensitivity is lower for cystic cervical metastases (73%) versus solid masses (90%), so repeat sampling may be necessary 1

If initial FNA is non-diagnostic or shows only necrosis:

• Proceed immediately to excisional biopsy rather than repeating FNA 2
• Excisional biopsy is preferred over incisional biopsy to reduce tumor spillage risk 1
• Do NOT perform open biopsy before imaging, as this worsens outcomes if malignancy is present 4

Essential Laboratory Testing

Obtain comprehensive initial labs for high-risk patients: 2

• Complete blood count with differential
• Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)
• Comprehensive metabolic panel including LDH
• Mandatory infectious disease screening: Hepatitis B, Hepatitis C, and HIV serology (required before any treatment) 2
• β2-microglobulin if lymphoma is suspected (prognostic marker) 1, 2

Special Consideration: Cystic Neck Masses

Continue aggressive evaluation of cystic neck masses until diagnosis is obtained—do NOT assume benign etiology. 1

The incidence of malignancy in cystic neck masses increases to 80% in patients >40 years old, with common etiologies including HPV-positive oropharyngeal carcinoma (62% of Waldeyer ring metastases are cystic), papillary thyroid carcinoma, and lymphoma 1, 4

If FNA shows benign cyst or is non-diagnostic:

• Repeat FNA with image guidance targeting cyst wall or solid components 1, 2
• If repeat FNA remains inadequate and malignancy is suspected, proceed to expedient open excisional biopsy 1

Additional Staging for Suspected Lymphoma

If imaging and clinical features suggest lymphoma: 1, 2

• Bone marrow biopsy is NOT required if PET-CT is performed 1, 2
• If PET-CT unavailable, bone marrow biopsy is mandatory with sample ≥20 mm length from posterior iliac spine 1
• Include appropriate immunohistochemistry on bone marrow specimen 1

Management of Lower-Risk Patients

For patients WITHOUT high-risk features: 1

• Advise patient of criteria that would trigger need for additional evaluation (development of high-risk features) 1
• Document a specific follow-up plan to assess resolution or final diagnosis 1
• Typical observation period is 2-4 weeks 1
• If lymph node persists beyond 4 weeks or develops high-risk features, proceed to full malignancy workup 1

Critical Pitfalls to Avoid

Do NOT prescribe empiric antibiotics without clear bacterial infection signs (warmth, erythema, tenderness, fluctuance), as this delays malignancy diagnosis and provides false reassurance 2, 7

Do NOT perform open excisional biopsy before imaging and FNA, as this worsens oncologic outcomes if malignancy is present and risks tumor spillage 4, 7

Do NOT assume soft texture excludes malignancy—cystic metastases are common and often soft 1, 4

Do NOT delay workup in patients >40 years with cystic masses—80% are malignant in this age group 1

Timeline for High-Risk Patients

Expedite workup with the following timeline: 2

• Imaging within days of presentation
• Tissue diagnosis within 1-2 weeks
• Definitive diagnosis and treatment planning within 3-4 weeks of initial presentation
• Urgent referral to otolaryngology for any neck mass present ≥2 weeks 2