Differential diagnosis of lymphadenomegaly

1. Big picture

Lymphadenomegaly means clinically enlarged lymph nodes. In the final exam, the examiner usually wants one practical skill: separate benign reactive lymph node enlargement from lymphoma, leukemia, metastatic cancer, tuberculosis, HIV/EBV, sarcoidosis, and autoimmune disease.

The key clinical question is:

Is this a short-lived reactive node, or is it persistent/progressive/systemic/malignant?

A normal lymph node can enlarge because of:

1. Reactive immune proliferation: infection, autoimmune disease.
2. Granulomatous inflammation: tuberculosis, sarcoidosis, fungal infection.
3. Malignant lymphoid proliferation: Hodgkin lymphoma, non-Hodgkin lymphoma, chronic lymphocytic leukemia.
4. Metastatic infiltration: carcinoma, melanoma, testicular/ovarian/breast/lung/gastrointestinal cancer.
5. Drug-related or systemic inflammatory reactions.

In lymphomas, nodes are often firm, slightly mobile, non-painful, and persistent; aggressive lymphomas may enlarge over weeks, while indolent lymphomas may persist for years. B symptoms include fever, night sweats, and >10% weight loss within 6 months. Fine-needle aspiration is not enough for diagnosing lymphoma; histology is required.

---