What is the appropriate management for a patient with bilateral enlarged cervical lymph nodes, left-sided tenderness, and ultrasound findings of increased fatty hila and cortical thickening?

Management of Bilateral Enlarged Cervical Lymph Nodes with Unilateral Tenderness and Ultrasound Findings

The ultrasound findings of preserved fatty hila and cortical thickening in bilateral cervical lymphadenopathy with unilateral tenderness strongly suggest reactive/inflammatory etiology rather than malignancy, but tissue diagnosis via fine-needle aspiration or excisional biopsy is mandatory to exclude malignancy and identify specific infectious causes. 1, 2

Immediate Risk Stratification

Critical features requiring aggressive workup:

• Nodes ≥1.5 cm persisting >2 weeks place the patient at increased risk for malignancy or chronic infection 1
• The presence of preserved fatty hilum on ultrasound is reassuring, as loss of fatty hilum strongly suggests malignancy 1, 2
• Cortical thickening with maintained architecture typically indicates reactive or infectious processes rather than malignant infiltration 3, 4

High-risk historical features mandating immediate investigation:

• Age >40 years 2
• Tobacco or alcohol use 2
• Immunocompromised status 2
• B symptoms (fever, night sweats, weight loss) 5, 1
• Prior head/neck malignancy 2

Diagnostic Algorithm

Step 1: Obtain Tissue Diagnosis

Fine-needle aspiration (FNA) is the preferred initial diagnostic method for palpable cervical lymph nodes, as it is accurate, economical, safe, and effective 5. However, excisional biopsy remains the gold standard for definitive diagnosis 1, 2.

• If FNA is inconclusive after repeated attempts, proceed directly to excisional biopsy 5
• For suspected mycobacterial disease, excisional biopsy is preferred over FNA 6
• Send fresh tissue in saline for flow cytometry and immunohistochemistry if malignancy is suspected 6

Step 2: Tuberculosis Testing

Obtain tuberculin skin testing (PPD) or interferon-gamma release assay to distinguish tuberculous from nontuberculous mycobacterial disease 1, 6. This is critical because:

• Approximately 80% of nontuberculous mycobacterial (NTM) lymphadenitis is due to Mycobacterium avium complex, typically presenting as unilateral, non-tender nodes 1
• In adults, >90% of culture-proven mycobacterial lymphadenitis is due to M. tuberculosis 1
• Common pitfall: Mistaking NTM for bacterial infection and treating with inappropriate antibiotics 1

Step 3: Additional Laboratory Evaluation

• Complete blood count with differential to assess for atypical lymphocytosis (viral), leukemia, or cytopenias 6
• HIV testing, especially in younger patients or those with risk factors 2
• EBV serology if infectious mononucleosis is suspected (bilateral cervical lymphadenopathy with constitutional symptoms) 1, 7

Step 4: Imaging Studies

CT neck with IV contrast is indicated if:

• Nodes are firm, fixed, or matted 2
• Need to evaluate deep extension or involvement of underlying structures 2
• Suspicion for head/neck primary malignancy 5

Chest radiograph should be obtained to evaluate for:

• Synchronous bronchial tumors 2
• Mediastinal involvement 2
• Tuberculosis or sarcoidosis 6

Management Based on Etiology

If Bacterial Lymphadenitis (Acute, Tender, Erythematous)

• Acute unilateral cervical lymphadenitis is caused by Staphylococcus aureus or Streptococcus pyogenes in 40-80% of cases 7, 8
• Provide coverage for both organisms with appropriate antibiotics 7, 8
• Do not empirically treat with antibiotics in the absence of signs suggesting acute bacterial infection (rapid onset, fever, overlying erythema) 1

If Viral Etiology (EBV, Other Viruses)

• Acute bilateral cervical lymphadenitis is usually caused by viral upper respiratory infection or streptococcal pharyngitis 7, 8
• Most cases are self-limited and require no treatment 7, 8
• Important: EBV infection carries long-term lymphoma risk; provide patient education about warning signs and consider follow-up every 6-12 months for 2-3 years 6

If Mycobacterial Disease

• For NTM lymphadenitis: Excisional biopsy without chemotherapy is the treatment of choice with 95% success rate 6
• For tuberculosis: Initiate anti-TB therapy while awaiting culture results if PPD is strongly positive and granulomatous disease is present 6

If Malignancy Suspected

• Immediate referral to hematology-oncology for nodes >1.5 cm, hard or matted nodes, B symptoms, or immunosuppression history 2
• If head/neck primary malignancy suspected, refer to ENT/surgical oncology 2
• PET/CT imaging is mandatory if B symptoms are present 5, 1

Critical Pitfalls to Avoid

1. Never delay tissue diagnosis in patients with nodes ≥1.5 cm persisting >2 weeks 1, 2
2. Do not treat empirically with antibiotics unless clear signs of acute bacterial infection are present 1
3. Do not miss NTM lymphadenitis by assuming bacterial infection—obtain tuberculosis testing 1, 6
4. Supraclavicular or posterior cervical lymphadenopathy carries much higher risk for malignancies than anterior cervical lymphadenopathy 7
5. Nodes >25 mm are always pathologic and require aggressive workup 1

Follow-Up Strategy

• If initial workup is negative and nodes persist, re-examine every 3 months and rebiopsy if there is evidence of further enlargement 5
• For patients with resolved lymphadenopathy after viral infection, consider surveillance for 6-12 months given potential lymphoma risk 6