• Clinical science



Lymphadenopathy is the enlargement of lymph nodes and most commonly occurs during benign, inflammatory processes. In pediatric patients, lymphadenopathy is usually caused by upper respiratory tract infections (see unilateral cervical lymphadenopathy). Painful, enlarged lymph nodes in adults, paired with signs of localized or systemic infection, are generally caused by some type of bacterial or viral infection. Malignancy must be considered in the case of painless, progressive lymph node swelling in the absence of signs of infection, in which case further diagnostic testing (e.g., serology, imaging, biopsy, and histological analysis) is necessary in order to make the diagnosis.


To remember the different causes of lymphadenopathy, think “MIAMI”: Malignancy (e.g., lymphomas), Infection (e.g., TB), Autoimmune disease (e.g., SLE), Miscellaneous (e.g., sarcoidosis), and Iatrogenic (medications).



Medical history

  • Duration of lymph node swelling
  • Symptoms:
    • Pain or tenderness: suggests benign inflammatory process
    • Acute fever, skin changes (common in viral infections)
    • Signs of inflammation in the lymph node drainage area
    • B symptoms
  • Underlying diseases
  • Medications
  • Travel history
  • Social and sexual history
  • Animal contacts

Physical examination

  • General: assess for both local inflammatory processes (e.g., enlarged neck lymph nodes due to tonsillitis) and signs of systemic disease (e.g., hepatomegaly and splenomegaly)
  • Peripheral lymph node examination:
    • Inspection
      • Visible enlargement: Lymph nodes should not be visible in healthy individuals, as they are only a few millimeters in diameter.
      • Local erythema, swelling, or lesion
    • Palpation
      • Gentle palpation using fingertips
      • The area to be examined should be relaxed to facilitate differentiation of the lymph node from the surrounding tissue (e.g., muscles, tendons).
      • Evaluation of size and level of pain consistency, and fixation.
      • Always examine the following regions :
        • Head and neck
        • Axillary region
          • Support the patient's relaxed arm with your own. Warn the patient that the exam might be uncomfortable.
          • With one hand, palpate high into the axillary region, pressing your fingers against the chest wall behind the pectoralis muscle and sliding downward.
          • Palpate the subclavicular, lateral, pectoral, and central lymph nodes. The central lymph nodes are typically the most palpable.
          • Move on to palpate the supratrochlear nodes, which are located 3 cm above the elbow.
          • A common cause of axillary lymphadenopathy is breast cancer.
        • Inguinal region

Characteristics Likely benign or inflammatory cause Likely malignant or mycobacterial cause










Cervical (anterior to the sternocleidomastoid muscle), inguinal

Cervical (dorsal to the sternocleidomastoid muscle), supraclavicular


Acute enlargement without long-term progression

Slow development combined with progressive enlargement

Soft, mobile, and tender lymph nodes are likely benign. Hard, nonmobile, nontender lymph nodes should raise concern for malignancy. Firm, nontender lymph nodes in patients with sarcoidosis or tuberculosis are exceptions.A palpable, firm lymph node in the left supraclavicular area is called a Virchow node and is classically associated with gastric carcinoma.

Further diagnostic testing

  • Acute, painful (localized or systemic) lymph node enlargement potentially associated with localized inflammation or infection (e.g., herpes labialis, pharyngitis).
  • Chronic, localized, nonprogressive lymph node enlargement: In general, no further diagnostic testing is necessary.
  • Painless, slowly progressing lymph node enlargement (generalized or localized) or in any other case of unexplained lymph node enlargement suggestive of malignant disease
    • Laboratory tests:
    • Imaging
      • Sonography: can help to characterize lymphadenopathy
        • Physiological lymph nodes or lymph node changes due to inflammation: sharply delimited, oval shape, presence of fatty hilum
        • Malignant lymph nodes: round , irregular, blurred margins, loss of fatty hilum
        • Allows for differentiation from other pathologic conditions (e.g., abscesses, cysts)
      • Chest x-ray: unexplained generalized lymphadenopathy requires evaluation of the hilar and mediastinal lymph nodes, especially if tuberculosis is suspected
      • If necessary, CT/MRI may be performed to better visualize lymph nodes.
    • Lymph node biopsy and histological analysis: if cancer is suspected or localized or generalized lymphadenopathy does not resolve in 3–4 weeks and imaging has been inconclusive


Differential diagnoses

Differential diagnoses according to characteristics of enlarged lymph nodes [1]

Painful Painless



Generalized lymphadenopathy is defined as the enlargement of more than two noncontiguous lymph node groups.

Differential diagnoses according to location of enlarged lymph nodes

See lymph node clusters in learning card on lymphatic system.

The differential diagnoses listed here are not exhaustive.