What is the initial workup for a patient presenting with lymphadenopathy and unplanned weight loss?

Initial Workup for Lymphadenopathy with Unplanned Weight Loss

The initial workup for a patient presenting with lymphadenopathy and unplanned weight loss should include a complete blood count, comprehensive metabolic panel, serum lactate dehydrogenase, appropriate imaging studies, and consideration of tissue biopsy if lymphadenopathy persists beyond four weeks or if concerning features are present. 1, 2

History and Physical Examination Focus

• Evaluate for B symptoms (fever >100.5°F for >2 weeks without evidence of infection, night sweats for >1 month without evidence of infection, unintentional weight loss of ≥10% within previous 6 months) 3, 4
• Determine duration and pattern of lymphadenopathy, with special attention to nodes that are >2 cm, hard, fixed, or matted 1, 5
• Assess for location of lymphadenopathy (supraclavicular, epitrochlear, and popliteal locations are particularly concerning for malignancy) 2, 5
• Distinguish between localized and generalized lymphadenopathy (generalized lymphadenopathy, defined as two or more involved regions, often indicates underlying systemic disease) 1, 2

Laboratory Studies

• Complete blood count with differential to evaluate for cytopenias or abnormal cells 4
• Comprehensive metabolic panel to assess organ function 4, 1
• Serum lactate dehydrogenase (LDH) as a potential marker for malignancy 4
• Consider erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) to evaluate for inflammatory processes 1, 2
• Hepatitis B virus testing if immunotherapy or chemotherapy is being considered 4

Imaging Studies

• CT scans with contrast of chest, abdomen, and pelvis to evaluate extent of lymphadenopathy and identify potential primary sites of malignancy 4, 1
• Consider PET-CT scan in selected cases, particularly when lymphoma is suspected 4, 3
• Chest X-ray as an initial screening tool 3, 1

Tissue Diagnosis

• Excisional lymph node biopsy is the preferred diagnostic procedure for persistent unexplained lymphadenopathy 3, 2
• Core needle biopsy may be considered as an alternative 3, 1
• Fine-needle aspiration alone is generally insufficient for definitive diagnosis of lymphoma 3, 2
• Bone marrow biopsy should be considered, especially when blood counts are abnormal 4

Special Considerations

• Supraclavicular lymphadenopathy carries the highest risk for malignancy and warrants more urgent evaluation 1, 5
• Lymphadenopathy persisting beyond 4 weeks without a clear cause requires further investigation 1, 2
• Avoid corticosteroid administration before diagnosis as it may mask histologic findings of lymphoma 1, 2
• Consider iatrogenic causes such as medications or recent vaccinations 1, 6

When to Suspect Malignancy

• Age >40 years 2, 5
• Presence of B symptoms (fever, night sweats, weight loss) 4, 3
• Hard, fixed, or matted lymph nodes 1, 5
• Supraclavicular location 2, 5
• Persistent lymphadenopathy (>4 weeks) without clear cause 1, 2
• Associated hepatosplenomegaly 4, 7

Approach to Specific Lymphoma Types

• If Hairy Cell Leukemia is suspected, immunophenotyping should include CD19, CD20, CD5, CD10, CD11c, CD22, CD25, CD103, CD123, cyclin D1, and CD200 4
• For Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, evaluate peripheral blood for lymphocytosis and assess for hepatosplenomegaly 4
• For Mantle Cell Lymphoma, consider GI tract involvement (though routine endoscopy is not recommended unless clinically indicated) 4