What causes enlarged lymph nodes?

Causes of Enlarged Lymph Nodes

Enlarged lymph nodes result from a broad spectrum of etiologies, with the majority being benign reactive processes, though malignancy must be systematically excluded based on specific clinical features and risk stratification.

Primary Etiologic Categories

Infectious Causes

• Localized infections are the most common cause of regional lymphadenopathy, including pneumonia, thoracic infections, and bacterial cervical lymphadenitis 1
• Viral infections such as measles, adenovirus, enterovirus, and Epstein-Barr virus commonly cause generalized lymphadenopathy 1
• In primary care settings, only 1% of patients with unexplained lymphadenopathy have malignancy, with most cases representing benign or infectious etiologies 2

Malignant Causes

• Lymphoma (both Hodgkin and non-Hodgkin) represents a critical malignant cause, particularly when nodes exceed 25 mm or demonstrate pathologic features 1
• Metastatic disease from solid tumors, with particular concern for seminoma and nonseminomatous germ cell tumors in young males with mediastinal lymphadenopathy 1
• Leukemia and other hematologic malignancies can present with generalized lymphadenopathy 3

Inflammatory and Autoimmune Conditions

• Granulomatous diseases including sarcoidosis cause lymph node enlargement >1 cm in short axis 1
• Collagen vascular diseases are associated with mediastinal and peripheral lymphadenopathy 1
• Kawasaki disease in children presents with cervical lymphadenopathy ≥1.5 cm diameter, usually unilateral 1

Cardiovascular and Pulmonary Associations

• Congestive heart failure is associated with enlarged mediastinal nodes >2 cm during various phases 1
• Interstitial lung diseases including usual interstitial pneumonia, nonspecific interstitial pneumonia, extrinsic allergic alveolitis, and cryptogenic organizing pneumonia correlate with lymphadenopathy severity 1

Drug Reactions and Hypersensitivity

• Drug hypersensitivity reactions can cause lymphadenopathy mimicking other serious conditions 1
• Mercury hypersensitivity (acrodynia) is a rare cause of lymph node enlargement 1

Size-Based Risk Stratification

Benign Features

• Nodes ≤15 mm in short axis are consistently reactive and benign in asymptomatic patients 1
• Benign morphologic characteristics include smooth well-defined borders, uniform homogeneous attenuation, and central fatty hilum 1

Concerning Features Requiring Further Evaluation

• Nodes >15 mm in short axis warrant closer follow-up or investigation 1
• Nodes >25 mm are consistently pathologic and require tissue diagnosis 1
• Loss of benign features such as absence of fatty hilum or irregular borders raises suspicion for malignancy 1

Critical Clinical Context

Red Flag Symptoms ("B Symptoms")

• Fever, night sweats, and weight loss suggest lymphoma or other systemic malignancy and mandate immediate advanced imaging (FDG PET/CT) 1, 4
• These symptoms override size criteria and require aggressive diagnostic workup 1, 4

Location-Specific Considerations

• Supraclavicular nodes have higher malignancy risk and warrant biopsy regardless of size 5
• Epitrochlear nodes similarly carry increased malignancy concern 5
• Mediastinal lymphadenopathy has 1-6% prevalence on screening CT, with majority being benign 1

Duration and Pattern

• Lymphadenopathy persisting >4 weeks requires imaging and laboratory evaluation 5
• Waxing and waning pattern with spontaneous regression suggests lymphomatoid papulosis rather than persistent malignancy 1, 4

Common Pitfalls to Avoid

• Do not assume all enlarged nodes are malignant: The majority of incidental mediastinal lymphadenopathy is benign, even when enlarged 1
• Avoid corticosteroids before definitive diagnosis as they mask histologic findings in lymphoma 5
• Do not rely on ultrasound alone for tracking response due to variability in imaging planes and lack of reproducibility 1
• Young males with mediastinal nodes require consideration of germ cell tumors in addition to lymphoma 1