Workup for Lymphadenopathy
The comprehensive workup for lymphadenopathy should include a thorough history and physical examination, laboratory studies, imaging, and biopsy when indicated, with the specific approach determined by whether the lymphadenopathy is localized or generalized. 1
Initial Assessment
History
- Duration and progression of lymph node enlargement
- Associated symptoms: fever, night sweats, weight loss (B symptoms)
- Recent infections or illnesses
- Medication history (potential drug reactions)
- Travel history
- Exposure to animals or insects
- History of autoimmune disorders
- Risk factors for HIV or hepatitis
- Family history of lymphoma or autoimmune disease
Physical Examination
- Complete examination of all lymph node regions
- Document size, consistency, tenderness, mobility, and location of enlarged nodes
- Particular attention to:
- Supraclavicular nodes (abnormal if palpable)
- Epitrochlear nodes (abnormal if >5 mm)
- Popliteal and iliac nodes (abnormal if palpable)
- Evaluate for hepatosplenomegaly
- Complete skin examination for rashes, lesions
Laboratory Studies
First-line Tests
- Complete blood count (CBC) with differential and reticulocyte count
- Comprehensive metabolic panel
- Erythrocyte sedimentation rate (ESR)
- C-reactive protein (CRP)
- Lactate dehydrogenase (LDH)
- HIV testing
- Hepatitis B and C screening
Additional Tests Based on Clinical Presentation
- Specific serologies for suspected infections
- Autoimmune panel if rheumatologic disease suspected
- Flow cytometry of peripheral blood if leukemic process suspected
- Serum protein electrophoresis
Imaging Studies
Initial Imaging
- Chest X-ray
- Contrast-enhanced CT scan of neck, chest, abdomen, and pelvis for unexplained or persistent lymphadenopathy
Advanced Imaging
- PET/CT scan for suspected malignancy or to guide biopsy
- Ultrasound for superficial lymphadenopathy (can help characterize nodes and guide biopsy)
Biopsy
Indications for Biopsy
- Persistent lymphadenopathy (>4 weeks) without obvious cause
- Supraclavicular or posterior cervical node enlargement
- Hard, fixed, or matted nodes
- Progressive enlargement
- Nodes >2 cm without signs of infection
- Age >40 years with unexplained lymphadenopathy
- Presence of B symptoms
Biopsy Options
- Fine-needle aspiration: Quick but limited sample
- Core needle biopsy: Better tissue architecture
- Excisional biopsy: Gold standard for lymphoma diagnosis
Special Considerations by Location
Cervical Lymphadenopathy
- Evaluate for head and neck infections
- Consider ENT examination
- In children with acute unilateral cervical lymphadenitis, antibiotics may be appropriate
Axillary Lymphadenopathy
- Evaluate for breast malignancy, upper extremity or chest wall infections
- Consider mammography in women
Inguinal Lymphadenopathy
- Often reactive; evaluate for lower extremity or genital infections
- Consider STI testing
Generalized Lymphadenopathy
- More likely to represent systemic disease (infection, autoimmune, malignancy)
- More extensive workup required including:
- Comprehensive infectious disease evaluation
- Rheumatologic workup
- Consider bone marrow examination
Important Caveats
- Corticosteroids should not be administered before a definitive diagnosis is established, as they may mask histological findings of lymphoma 1
- In patients with suspected lymphoma, excisional biopsy is preferred over fine-needle aspiration
- Antibiotics should be reserved for cases with clear evidence of bacterial infection
- Risk factors for malignancy include age >40 years, male sex, white race, supraclavicular location, and presence of B symptoms 1
- Certain conditions like IgG4-related disease may require specific immunohistochemical studies 2
- In resource-limited settings, prioritize history, physical examination, and basic laboratory tests before advanced imaging 3
Remember that while most cases of lymphadenopathy are benign and self-limited, a systematic approach is essential to identify serious underlying conditions that require specific treatment.