What is the recommended approach for evaluating neck lymphadenopathy (lymph node enlargement in the neck)?

Evaluation of Neck Lymphadenopathy in Adults

All adults presenting with neck lymphadenopathy require a systematic risk stratification approach beginning with detailed history and physical examination to identify high-risk features that mandate immediate workup for malignancy, as missing or delaying cancer diagnosis carries greater consequences than false-positive evaluations. 1

Initial Risk Stratification: Identify High-Risk Features

History-Based Red Flags

• Duration ≥2 weeks without significant fluctuation or uncertain duration 1, 2
• Absence of infectious etiology 1
• Age >40 years 1
• Tobacco use, alcohol abuse, or immunocompromised status 1
• HPV-related risk factors: increased number of sexual partners, oral sex exposure 1
• Associated symptoms: hoarseness, otalgia, hearing loss, dysphagia, odynophagia, weight loss, hemoptysis, nasal congestion, unilateral epistaxis, intraoral swelling/ulceration, new numbness in oral cavity 1
• History of prior head and neck malignancy or skin cancer of scalp/face/neck 1

Physical Examination Red Flags

• Size >1.5 cm (upper limit of normal for jugulodigastric node) 1
• Firm or hard consistency 1
• Fixation to adjacent tissues (reduced mobility) 1
• Ulceration of overlying skin 1
• Multiple, grouped, or matted lymph nodes 1
• Nontender mass (more suspicious than tender) 1
• Continued increase in size 1

Critical caveat: Soft, cystic masses can be malignant, particularly in HPV-positive oropharyngeal cancer where up to 62% of metastases present as cystic masses. 3 Do not assume soft texture equals benign disease. 3

Mandatory Workup for High-Risk Patients

Step 1: Targeted Physical Examination

Perform or refer for complete visualization of upper aerodigestive tract mucosa including larynx, base of tongue, and pharynx using flexible laryngoscopy. 1 This examination should include:

• Face inspection for swelling, edema, ulcerations, pigmented lesions 1
• Scalp examination for ulcerations or pigmented lesions 1
• Oral cavity examination with dentures removed, palpation of floor of mouth 1
• Oropharynx examination with mouth open but tongue NOT protruded (protruding obscures view) 1
• Assessment for tonsil asymmetry, masses, or ulcers 1
• Palpation of oral tongue, base of tongue, tonsils, and thyroid gland 1

Step 2: Imaging (Strong Recommendation)

Order contrast-enhanced CT or MRI of the neck immediately. 1, 4 Both modalities have similar diagnostic value for neck evaluation. 1 CT and MRI are complementary; discuss with a head and neck radiologist. 1

Add chest CT to assess for distant metastases in high-risk tumors (presence of neck adenopathy) or second lung primary in heavy smokers. 1 FDG-PET combined with contrast-enhanced chest CT has higher sensitivity than either modality alone. 1

Consider FDG-PET/CT when:

• Carcinoma of unknown primary is suspected (to direct specific mucosal biopsy) 1
• Lymphoma is suspected 4
• Evaluating neck response 10-12 weeks after completing radiotherapy/chemoradiotherapy 1

Step 3: Tissue Diagnosis (Strong Recommendation)

Perform ultrasound-guided fine-needle aspiration (FNA) instead of open biopsy when diagnosis remains uncertain after imaging. 1, 4 For cystic masses, direct FNA at solid components or cyst wall. 3

Critical pitfall: Do NOT perform open excisional biopsy before imaging and FNA, as this worsens outcomes if malignancy is present and risks tumor spillage. 3

Step 4: Ancillary Laboratory Tests

• Complete blood count with differential (evaluate for hematologic malignancies) 4
• Serum LDH (elevated in lymphoma, provides prognostic information) 4
• Liver enzymes, serum creatinine, albumin, coagulation parameters, TSH 1

Step 5: Pathology Assessment

For tissue obtained:

• p16 immunohistochemistry on all oropharyngeal squamous cell carcinomas (reliable surrogate for HPV positivity) 1
• For neck metastases of unknown origin with p16 positivity: confirm with specific HPV test (DNA, RNA, or ISH) 1
• EBER using ISH to exclude nasopharyngeal cancer when neoplastic lymph node has unknown primary 1

Step 6: If Diagnosis Still Uncertain

Recommend examination of upper aerodigestive tract under anesthesia before open biopsy for patients at increased risk without diagnosis identified through FNA, imaging, and ancillary tests. 1

Management of Low-Risk Patients

For patients WITHOUT high-risk features:

• Advise patients of criteria triggering need for additional evaluation 1
• Document follow-up plan to assess resolution or final diagnosis 1
• Do NOT routinely prescribe antibiotics unless clear signs and symptoms of bacterial infection are present 1

Critical pitfall: Empiric antibiotic therapy for fixed neck mass without clear infection delays cancer diagnosis and worsens outcomes. 3 Most neck masses in adults are neoplastic, not infectious. 1

Special Consideration: Cystic Masses

Continue evaluation of cystic neck masses until diagnosis is obtained; do NOT assume benign. 1 Up to 80% of cystic neck masses in patients >40 years are malignant. 3 Cystic metastases occur in:

• HPV-positive oropharyngeal squamous cell carcinoma (most common) 3
• Papillary thyroid carcinoma 3
• Lymphoma 3

Patient Education

For high-risk patients, explain the significance of increased malignancy risk and rationale for recommended diagnostic tests. 1 The risk of missing or delaying malignancy diagnosis outweighs the risk of false-positive clinical diagnosis and subsequent patient anxiety. 1