Common Causes of Benign Lymph Node Enlargement
Benign lymph node enlargement most commonly results from infectious processes, inflammatory conditions, and reactive changes, with the specific etiology often determined by the clinical context, patient demographics, and associated findings. 1
Infectious Etiologies
Infections represent one of the primary causes of reactive lymph node enlargement in both children and adults. 2 The most frequent infectious causes include:
- Pneumonia and other thoracic infections commonly cause mediastinal and hilar lymphadenopathy >1 cm in short axis 1
- Tuberculosis is among the most frequent infections resulting in thoracic lymphadenopathy 3
- Fungal diseases, particularly histoplasmosis and coccidioidomycosis, frequently cause lymph node enlargement 3
- Viral infections can produce reactive lymphadenopathy in various nodal stations 3
Inflammatory and Granulomatous Diseases
Granulomatous diseases are a major category of benign lymph node enlargement:
- Sarcoidosis is a relatively frequent cause of lymphadenopathy in young adults, typically presenting with multiple, symmetrical enlarged nodes 3
- Collagen vascular diseases can cause reactive lymphadenopathy 4
- Drug reactions may trigger lymph node enlargement 3
Cardiovascular and Pulmonary Conditions
Enlarged mediastinal nodes (>2 cm) have been described in association with various phases of congestive heart failure. 1 Additional pulmonary causes include:
- Interstitial lung diseases including usual interstitial pneumonia, nonspecific interstitial pneumonia, respiratory bronchiolitis, cryptogenic organizing pneumonia, and desquamative interstitial pneumonia 1
- Chronic obstructive pulmonary disease can be associated with lymphadenopathy 3
- Silicosis causes characteristic lymph node enlargement 3
- The prevalence and extent of lymphadenopathy in interstitial lung disease correlate with disease severity 1
Other Benign Causes
- Amyloidosis can present with lymph node enlargement 3
- Castleman's disease is a less common but important benign cause 3
- Accessory breast tissue and benign lesions within accessory tissue can present as axillary masses 1
- Reactive changes to implant materials (silicone or polyurethane) can cause lymph node enlargement, sometimes associated with implant rupture 1
- Recent mRNA COVID-19 vaccination commonly causes reactive axillary lymphadenopathy, typically with mild FDG avidity (SUVmax ~2.6) 5
Key Distinguishing Features of Benign Nodes
Most benign nodes demonstrate characteristic imaging features: 1
- Smooth and well-defined borders
- Uniform and homogeneous attenuation
- Central fatty hilum present
- Short axis diameter typically <15 mm 1, 6
Critical Clinical Pitfall
A major pitfall is falsely attributing lymph node enlargement to benign causes (such as recent vaccination) when malignancy is actually present, which can delay cancer care and allow disease progression. 5 When lymph nodes exceed 15 mm in short axis, demonstrate loss of fatty hilum, have irregular borders, or are associated with concerning clinical features, further evaluation with imaging or biopsy is warranted regardless of potential benign explanations. 1, 6