What is the treatment for enlarged lymph nodes?

Treatment of Enlarged Lymph Nodes

The treatment of enlarged lymph nodes depends entirely on the underlying cause—benign reactive nodes require observation only, while malignant lymphadenopathy demands specific therapy directed at the diagnosed malignancy. 1, 2

Initial Diagnostic Workup

The first priority is establishing whether lymphadenopathy is benign or malignant, which determines all subsequent management:

History and Physical Examination

• Document B-symptoms (fever, night sweats, weight loss >10% body weight), which strongly suggest lymphoma or other malignancy 1, 2
• Assess for immunosuppression history (HIV, organ transplantation, immunosuppressive medications), as this increases risk of lymphoproliferative disorders 1, 2
• Note duration and pattern of lymphadenopathy—waxing/waning suggests reactive etiology, while progressive enlargement raises malignancy concern 2
• Examine for hepatosplenomegaly, which indicates systemic disease 1, 2
• Measure lymph node size: nodes >1.5 cm in long axis or >1.0 cm in short axis warrant further evaluation 2
• Critical red flag: Supraclavicular lymphadenopathy or rock-hard, rubbery, or fixed nodes strongly suggest malignancy 3

Laboratory Testing

• Complete blood count with differential to identify hematologic abnormalities 1, 2
• Lactate dehydrogenase (LDH), which is elevated in lymphoma and other malignancies 1, 2
• Consider β2-microglobulin in suspected lymphoproliferative disorders 2

Imaging Studies

• CT scan is the imaging method of choice for mediastinal and deep lymphadenopathy, using size criteria >15 mm short axis to guide management 1
• Ultrasound serves as excellent first-line imaging for accessible peripheral nodes, assessing size, shape, borders, and internal architecture 2
• PET/CT demonstrates 88% sensitivity and 98% specificity for lymphoma and should be used for staging FDG-avid malignancies 1, 2

Tissue Diagnosis Strategy

Excisional biopsy is the gold standard for definitive diagnosis and should be pursued when lymphoma is suspected or when fine needle aspiration is non-diagnostic. 1, 2

Biopsy Approach

• Ultrasound-guided fine needle aspiration (FNA) has 93% sensitivity and 91% specificity for palpable nodes and serves as an appropriate first-line procedure 1, 2
• However, excisional biopsy is mandatory for suspected lymphoma to preserve nodal architecture necessary for accurate WHO classification and immunohistochemistry 4, 1
• Surgical excisional biopsy significantly reduces investigation time (1.25 months) compared to needle biopsy followed by surgery (3 months) 5
• Core biopsies may be acceptable only in patients requiring emergency treatment or those unsuitable for curative therapy 4

Common Pitfall

Enlarged lymph nodes may be hyperplastic rather than neoplastic, and normal-sized nodes may harbor malignant cells—CT has only 41-67% sensitivity for detecting nodal metastases based on size alone 4, 1

Treatment Based on Diagnosis

Benign Reactive Lymphadenopathy

• Observation for 2-4 weeks is appropriate for unexplained localized cervical lymphadenopathy with benign clinical features 3
• No specific treatment required beyond addressing underlying infection or inflammatory condition 6, 3
• Re-examine if nodes persist beyond 4 weeks or enlarge during observation 3

Malignant Lymphadenopathy

Large B-Cell Lymphoma

• CHOP chemotherapy combined with rituximab every 21 days for 8 cycles is the current standard for CD20+ large cell non-Hodgkin's lymphoma of all stages 4
• For T-cell lymphoma, CHOP without rituximab remains standard 4
• Avoid dose reductions for hematological toxicity; use prophylactic growth factors for febrile neutropenia 4
• Radiotherapy consolidation to bulky disease sites has not proven benefit 4

Metastatic Solid Tumors

• If lymph nodes are positive for metastatic squamous cell carcinoma on FNA, regional lymph node dissection should be considered, typically performed at time of primary tumor excision 4
• For lung cancer with nodal metastases, treatment follows stage-appropriate protocols with chemotherapy and/or radiation 4

Response Assessment

• For lymphoma, perform radiological evaluation after 2-4 cycles and after final cycle of chemotherapy 4
• Response criteria include at least 50% reduction in lymphadenopathy for partial response 1
• Repeat initially pathologic bone marrow or spinal tap at end of treatment 4

Special Considerations

When to Rebiopsy

• If regional lymph nodes are initially negative on FNA but subsequently enlarge, rebiopsy is indicated 4
• Examine lymph nodes every 3 months in high-risk patients with negative initial biopsy 4

Mediastinal Lymphadenopathy

• Enlarged mediastinal nodes on CT must be sampled with biopsy to avoid overstaging, as size alone is insufficient for diagnosis 4
• Mediastinoscopy, mediastinotomy, thoracoscopy, or transbronchial biopsy selection depends on lymph node location 4