What are the recommendations for managing persistently swollen lymph nodes?

Management of Persistently Swollen Lymph Nodes

Persistently swollen lymph nodes require tissue diagnosis through biopsy when they persist beyond 4 weeks, exceed 2 cm in size, or demonstrate concerning features such as firm consistency, fixation to surrounding tissues, or supraclavicular/epitrochlear location. 1, 2

Initial Clinical Assessment

History Taking Priority Points

• Duration of lymphadenopathy (persistence >4 weeks significantly increases malignancy risk) 2
• Constitutional symptoms: fever >38.3°C, unintentional weight loss, drenching night sweats (B symptoms suggest lymphoma) 3, 2
• Age: children 1-5 years are at peak risk for nontuberculous mycobacterial (NTM) lymphadenitis; adults >40 years have higher malignancy risk 4, 2
• Occupational and animal exposures for infectious etiologies 5, 2
• Recent infections, vaccinations, medications, sexual history, and travel 2

Physical Examination Red Flags

• Size >2 cm (particularly concerning in children where >1.5 cm warrants evaluation) 4, 2
• Hard or firm consistency (suggests malignancy or granulomatous disease) 4, 2
• Fixed to adjacent tissues or matted/fused nodes 1, 2
• Supraclavicular or epitrochlear location (high malignancy association) 2
• Ulceration of overlying skin 1
• Determine if localized versus generalized (generalized suggests systemic disease) 2

Diagnostic Algorithm

For Localized Cervical Lymphadenopathy Persisting ≥2 Weeks

Immediate specialist referral to otolaryngology is mandatory 1. The common pitfall is prescribing additional antibiotics without bacterial infection signs, which delays malignancy diagnosis 1.

Specialist Workup Should Include:

• Targeted physical examination with direct visualization of larynx, base of tongue, and pharynx mucosa 1
• Cross-sectional imaging: contrast-enhanced CT or MRI for patients at increased malignancy risk 1
• Fine-needle aspiration (FNA) preferred over open biopsy for initial tissue sampling 1
• Immunophenotypic analysis essential for lymphoma subtype differentiation 1
• PET-CT valuable for evaluating suspicious findings on other imaging 1

For Suspected Lymphoma

PET-CT is the gold standard for staging FDG-avid lymphomas (all histologies except CLL/SLL, lymphoplasmacytic lymphoma, mycosis fungoides, and marginal zone lymphomas) 3. Contrast-enhanced CT should be included for accurate nodal measurement 3.

Required Laboratory Studies:

• Complete blood count, comprehensive metabolic panel (renal and liver function) 1
• Lactate dehydrogenase (LDH) - critical prognostic marker 1
• Hepatitis B, C, and HIV serology - required before immunotherapy/chemotherapy 1
• Erythrocyte sedimentation rate 1

Tissue Diagnosis Requirements:

• Excisional or incisional biopsy preferred to provide adequate tissue for morphology, immunohistochemistry, flow cytometry, and molecular studies 3
• Core-needle biopsy acceptable when excisional biopsy not feasible, but nondiagnostic sample must be followed by excisional biopsy 3
• Fine-needle aspiration inadequate for initial lymphoma diagnosis 3
• Bone marrow biopsy (≥20 mm) if lymphoma or leukemia suspected 1

For Children with Unilateral Cervical Lymphadenopathy

Consider NTM lymphadenitis in children aged 1-5 years with unilateral, non-tender cervical adenopathy 4. The critical error is mistaking this for bacterial infection and treating with inappropriate antibiotics 4.

Diagnostic Approach:

• Tuberculosis testing (PPD tuberculin skin test) to differentiate TB from NTM 4
• Excisional biopsy without chemotherapy is the recommended treatment with ~95% success rate 4
• For nodes ≥5 cm or difficult anatomical sites: consider MRI or CT before surgery 4

Follow-Up Strategy

Post-Treatment Surveillance

Routine surveillance scans are strongly discouraged due to false-positive rates >20%, leading to unnecessary investigations, radiation exposure, and patient anxiety 3. Follow-up scans should only be prompted by clinical indications 3.

For Curable Histologies (Hodgkin Lymphoma, DLBCL):

• Every 3 months for first 2 years 3
• Every 6 months for years 3-5 3
• Annually thereafter to monitor for late relapse and treatment-related adverse effects 3

For Incurable Histologies (Follicular, Mantle-Cell Lymphoma):

• Every 3-6 months indefinitely, determined by pretreatment risk factors and treatment response 3
• Judicious use of scans may be considered for asymptomatic intra-abdominal or retroperitoneal residual disease 3

For Benign Reactive Lymphadenopathy

If lymph node completely resolves, schedule one additional follow-up in 2-4 weeks to monitor for recurrence 4. Reactive lymphadenopathy from respiratory infections typically resolves within days of completing treatment 4.

Critical Caveats

• Never assume a cystic neck mass is benign without definitive diagnosis, as this delays malignancy diagnosis 1
• Partial resolution after antibiotics may represent infection in underlying malignancy - proceed to definitive workup if not completely resolved 1
• Avoid corticosteroids as they can mask histologic diagnosis of lymphoma or malignancy 2
• Even with benign ultrasound findings, continued evaluation is necessary until definitive diagnosis obtained 1
• In children with granulomatous disease and strongly positive PPD, consider anti-TB therapy while awaiting culture results 4