Enlarged Lymph Nodes (Lymphadenopathy): Causes and Evaluation

Lymphadenopathy (nodes >1 cm in short axis) reflects immune activation or infiltration. Etiology is categorized by mechanism.

Major Etiologic Categories

1. Infections (Most Common):
   • Viral: EBV (mononucleosis), CMV, HIV, HSV, measles, rubella.
   • Bacterial: Strep (cervical), TB (scrofula), cat-scratch (Bartonella), syphilis.
   • Fungal/Parasitic: Histoplasmosis, toxoplasmosis.
2. Malignancy:
   • Primary: Hodgkin/Non-Hodgkin lymphoma, leukemia.
   • Metastatic: Squamous cell (H&N), breast, melanoma, lung, GI — nodes draining primary site.
3. Autoimmune/Inflammatory: SLE, RA, Still's disease, sarcoidosis, IgG4-related disease, Kawasaki.
4. Drug-Induced: Phenytoin, allopurinol, penicillin, sulfonamides (serum sickness-like, DRESS).
5. Storage/Infiltrative: Gaucher, Niemann-Pick, amyloidosis.
6. Benign Reactive: Post-vaccination, local skin infection, dermatitis.

Red Flags for Malignancy

• Size >2 cm, firm/hard, fixed/matted, non-tender.
• Supraclavicular location (Virchow's node → GI/lung cancer).
• Constitutional symptoms: weight loss, night sweats, fever.
• Duration >2-4 weeks without resolution or progression.
• Age >40 (higher pre-test probability).

Evaluation Approach

1. History: exposure, travel, medications, systemic symptoms.
2. Exam: location, size, consistency, mobility, tenderness, skin changes.
3. Initial labs: CBC, ESR/CRP, LFTs, LDH, HIV, TB test, heterophile (if mono suspected).
4. Imaging: US (first-line), CT if deep nodes or staging needed.
5. Biopsy: Excisional preferred (architecture); FNA if lymphoma low suspicion or inaccessible.

Most lymphadenopathy is benign/reactive. Persistent or concerning features warrant timely biopsy.