What is the evaluation and treatment approach for lymph node swelling?

Evaluation and Treatment of Lymph Node Swelling

For patients presenting with lymph node swelling, obtain an excisional lymph node biopsy when malignancy is suspected, as fine needle aspiration is inadequate for definitive diagnosis of lymphoma and should only be used in emergency situations. 1

Initial Clinical Assessment

Key History Elements

• Duration and progression: Waxing and waning lesions suggest lymphoproliferative disorders, while persistent enlargement raises concern for malignancy 2
• Constitutional symptoms: Fever >101°F (38.3°C), night sweats, weight loss (B symptoms) indicate more aggressive disease 2
• Prior malignancy history: Particularly Hodgkin lymphoma, non-Hodgkin lymphoma, or breast cancer 2
• Immunosuppression status: HIV, organ transplantation, or immunosuppressive therapy increases risk of lymphoproliferative disorders 2
• Occupational exposures: Animal contact may suggest infectious etiologies 3

Physical Examination Priorities

• Node characteristics: Size (nodes >1.5 cm in greatest diameter warrant further investigation), consistency, tenderness, mobility, and distribution pattern 2
• Multiple anatomic regions: Generalized lymphadenopathy (>1 region) suggests systemic disease 4
• Associated findings: Hepatosplenomegaly (spleen >13 cm vertical length on imaging suggests involvement) 2
• Skin examination: Patches, plaques, or papulonodular lesions may indicate cutaneous lymphoproliferative disorders 2

Diagnostic Workup Algorithm

Laboratory Investigations (All Patients)

• Complete blood count with differential: Assess for cytopenias or lymphocytosis 1
• Lactate dehydrogenase (LDH): Elevated levels suggest lymphoproliferative disease 2, 1
• Comprehensive metabolic panel including uric acid 1
• Infectious screening: HIV, hepatitis B and C serology 1

Tissue Diagnosis Strategy

Primary approach: Excisional lymph node biopsy is mandatory for suspected lymphoma, providing adequate tissue for histopathology, immunohistochemistry (including CD20), and WHO classification 1. The entire node should be submitted fresh for both frozen and formalin-fixed analysis 2.

Avoid: Fine needle aspiration or core biopsies are inappropriate for lymphoma diagnosis except in rare emergency situations requiring immediate treatment 2, 1. Open biopsy should not be the initial approach due to higher complication risk 5.

Exception: If lymphoma is suspected based on clinical features, core needle biopsy with ultrasound guidance may be preferred over FNA (sensitivity 92% vs 74%) 5.

Imaging Studies

For suspected lymphoma (stages I-II):

• CT chest, abdomen, and pelvis with contrast 1
• Consider PET-CT for FDG-avid histologies to assess metabolic activity 2
• Bone marrow aspirate and biopsy (though PET-CT may be adequate for bone marrow assessment in some cases) 2, 1

For localized disease without systemic symptoms:

• Ultrasound to characterize mass, guide sampling, and identify additional nodes (95% sensitivity for core biopsy guidance) 5
• Chest x-ray may suffice for low-risk presentations 2

For advanced disease (stages III-IV):

• Comprehensive CT or PET-CT imaging is essential 1
• Brain MRI if neurological symptoms present 2

Common Pitfalls to Avoid

• Inadequate tissue sampling: Ensure the pathologist receives sufficient material for immunohistochemistry and molecular studies; coordinate immediate processing with an experienced pathology institute 2
• Missing extranodal involvement: Always assess for splenomegaly (palpation and imaging), hepatomegaly, and bone marrow involvement 2
• Incomplete staging: Lymph node levels should be specified separately (e.g., neck dissections, colectomy specimens) 2
• Overlooking infectious causes: In endemic areas, tuberculosis is the most common cause of lymphadenopathy (52.7% in some series), followed by reactive hyperplasia (16.1%) 6

Treatment Approach Based on Diagnosis

Follicular Lymphoma

Limited stage (I-II): Extended field radiotherapy is treatment of choice with curative potential 2, 1

Advanced stage (III-IV): Initiate chemotherapy only when symptomatic (B symptoms, cytopenias, bulky disease, or progression), as 15-20% show spontaneous regression 2, 1. Primary regimens include COP, CHOP, or single agents like fludarabine 1.

Large Cell Non-Hodgkin Lymphoma

All stages: R-CHOP every 21 days for 8 cycles is standard for CD20+ disease 1

Response Monitoring

• Imaging frequency: After every 2-4 cycles, at treatment completion, and when response is uncertain 1
• PET-CT for FDG-avid histologies: Use 5-point scale (Deauville criteria) for response assessment 2
• Progressive disease criteria: ≥50% increase in sum of perpendicular diameters from nadir, or new lesions >1.5 cm 2

Follow-Up Schedule

Years 0-2: History and physical examination every 3 months 1

Years 3-5: Every 6 months 1

Beyond 5 years: Annually, with attention to transformation and secondary malignancies 2, 1

Laboratory monitoring: CBC and LDH at 3,6,12, and 24 months, then as clinically indicated 1

Surveillance imaging: At 6,12, and 24 months post-treatment; routine imaging beyond this is not recommended for asymptomatic patients 2, 1