Differential Diagnosis for Enlarged Lymph Nodes

Malignant Causes

Lymphoma (Hodgkin and non-Hodgkin) represents a primary concern, particularly in adults with persistent lymphadenopathy and in young males with mediastinal involvement 1
Post-transplant lymphoproliferative disorders include reactive plasmacytic hyperplasia, infectious mononucleosis-like lesions, polymorphic PTLD, and monomorphic PTLD (B-cell and T-cell lymphomas) 2
Adult T-cell leukemia/lymphoma (HTLV-I associated) should be considered in endemic areas 2
Germ cell tumors (seminoma and nonseminomatous) are of primary concern in young males with mediastinal lymphadenopathy 1

Bacterial cervical lymphadenitis can mimic other causes of cervical lymphadenopathy 3, 4
Pneumonia and other thoracic infections commonly cause mediastinal lymphadenopathy >1 cm 1
Epstein-Barr virus (infectious mononucleosis) 3, 4
Measles, adenovirus, enterovirus 3, 4
HIV-related lymphadenopathy 5
Leptospirosis 3, 4

Sarcoidosis frequently causes mediastinal lymphadenopathy >1 cm 1
Kawasaki disease presents with cervical lymphadenopathy ≥1.5 cm diameter, usually unilateral and confined to the anterior cervical triangle 3, 4
Juvenile rheumatoid arthritis 3, 4
Drug hypersensitivity reactions 3, 4
Methotrexate and other immunosuppressive therapy can cause Hodgkin's lymphoma-like lesions 2

Congestive heart failure can cause enlarged mediastinal nodes >2 cm 1
Diffuse interstitial lung diseases including usual interstitial pneumonia, nonspecific interstitial pneumonia, extrinsic allergic alveolitis, respiratory bronchiolitis, cryptogenic organizing pneumonia, and desquamative interstitial pneumonia, with prevalence and extent correlating with disease severity 1
Toxic shock syndrome 3, 4
Staphylococcal scalded skin syndrome 3, 4
Stevens-Johnson syndrome 3, 4
Rocky Mountain spotted fever 3, 4
Mercury hypersensitivity reaction (acrodynia) 3, 4

Lymph nodes >1.5 cm in short axis diameter require workup for potential malignancy 6
Nodes ≤15 mm were always reactive in one study, while nodes >25 mm were always pathologic 1, 6
15 mm short-axis threshold serves as a key decision point in management algorithms 1, 6
Loss of fatty hilum is concerning 1, 6
Round shape (rather than oval) independently predicts malignancy 6
Heterogeneous echogenicity on ultrasound 6
Central necrosis strongly suggests malignancy 6
Convex pleural interface (versus straight or concave) suggests malignant hilar nodes 7
B symptoms (fever, night sweats, weight loss) suggest lymphoma and require PET/CT imaging 1, 6

Do not rely on size alone: Normal-sized nodes can harbor microscopic metastases, and enlarged nodes may be hyperplastic rather than neoplastic 1, 7
Benign reactive nodes with follicular hyperplasia can appear enlarged and mimic malignancy 7
In patients with known malignancy, benign nodes are typically smaller than malignant nodes, but this distinction is less reliable for incidental findings 1