From the Guidelines
The initial workup for reactive lymphadenopathy should begin with a thorough history and physical examination, focusing on the duration, location, and characteristics of the lymph node enlargement, as recommended by the most recent guidelines 1.
Initial Evaluation
The initial evaluation should include:
- A thorough physical examination with attention to node-bearing areas, size measurements of the liver and spleen, and performance status evaluation 1
- Laboratory tests, such as:
- Complete blood count with differential
- Comprehensive metabolic panel
- Erythrocyte sedimentation rate
- C-reactive protein to assess for infection or inflammation
- Specific serologic tests for common infectious causes should be ordered based on clinical suspicion, including Epstein-Barr virus, cytomegalovirus, HIV, toxoplasmosis, and tuberculosis testing
Imaging Studies
Imaging studies, such as:
- Ultrasound to characterize the lymph nodes, assessing for features like size, shape, hilum preservation, and vascularity
- Computed tomography (CT) scan of the neck, thorax, abdomen, and pelvis, as recommended by the ESMO guidelines for follicular lymphoma 1
- Positron emission tomography (PET)–CT, which improves the accuracy of staging for nodal and extranodal sites, as recommended by the ESMO guidelines for follicular lymphoma 1
Biopsy
For persistent lymphadenopathy (lasting more than 4-6 weeks), unexplained constitutional symptoms, or concerning features like hard, fixed nodes, excisional biopsy should be considered, as it is the most definitive diagnostic method 1. Fine needle aspiration may be used initially but has limitations.
Follow-up
Reassurance and follow-up in 2-4 weeks is appropriate for patients with likely benign causes and no concerning features. The rationale for this approach is that most reactive lymphadenopathy is benign and self-limiting, often due to localized or systemic infections, but persistent or atypical presentations require further investigation to rule out malignancy, autoimmune conditions, or rare infections 1.
From the Research
Initial Workup for Reactive Lymphadenopathy
The initial workup for reactive lymphadenopathy involves a combination of clinical evaluation, laboratory tests, and imaging studies. The following steps are recommended:
- Classification of lymphadenopathy as localized or generalized, with localized lymphadenopathy evaluated for etiologies associated with the region involved according to lymphatic drainage patterns 2
- Evaluation of risk factors for malignancy, including age older than 40 years, male sex, white race, supraclavicular location of the nodes, and presence of systemic symptoms such as fever, night sweats, and unexplained weight loss 2
- Physical examination to identify palpable supraclavicular, popliteal, and iliac nodes, as well as epitrochlear nodes greater than 5 mm in diameter 2
- Laboratory tests, including blood tests, and imaging studies, such as ultrasound or computed tomography (CT) scans, to evaluate the extent of lymphadenopathy and guide further management 2, 3
- Consideration of biopsy options, including fine-needle aspiration, core needle biopsy, or open excisional biopsy, depending on clinical presentation, location of the lymphadenopathy, and underlying risk factors 2
Special Considerations
- In patients with HIV infection, consideration of infectious, inflammatory, and neoplastic causes of lymphadenopathy, and evaluation of CD4 lymphocyte counts and radiologic features to identify likely causes 4
- In patients with rheumatologic disorders, consideration of lymphadenopathy as a primary manifestation of an underlying immune-mediated disease or indication of an infectious or neoplastic complication requiring differing management 5
- In all patients, a detailed history and physical examination to screen for lymphadenopathy and guide further evaluation and management 6, 3