Lymphadenopathy in Adults

Background

• Lymphadenopathy is a common finding that is characterized by abnormality in size or consistency of ≥ 1 lymph nodes. It may be localized to 1 region or generalized, involving ≥ 2 regions.
• Around 0.6% of patients reported to present to their primary care physician each year with lymphadenopathy. About 75% of lymphadenopathies reported to be localized, of which 50% are reported to occur in head and neck region, and 25% are reported to be related to systemic disease.
• The human body contains 600-800 lymph nodes, most of which are located at the base of limbs, neck, and around major blood vessels.
• Lymph nodes drain lymphatic vessels, which transport interstitial fluid, immune cells, and macromolecules to lymph nodes via collecting vessels, and from these back to the blood circulation via thoracic duct and the right lymphatic trunk.
• There are a wide range of causes that contribute to development of lymphadenopathy, which are typically benign and self-limiting. However, lymphadenopathy may indicate presence of a more serious condition such as malignancy.
• "MIAMI" may be useful mnemonic to organize common differential diagnoses:
  • malignancies
  • infections
  • autoimmune disorders
  • miscellaneous
  • iatrogenic

Evaluation

• Cause of lymphadenopathy may be evident on history and physical exam alone or found incidentally in imaging.
• Lymph node features, as well as location (and single versus multiple nodes) of affected lymph nodes present on initial exam, may help point towards a cause.
• Additional diagnostic workup may include lab tests (including blood, urine, and/or sputum), imaging, and/or biopsy.
• Specific diagnostic approach is based on initial exam and clinical suspicion of cause.
  • In patients suspected of having malignancy:
    • perform testing to confirm diagnosis including complete blood count (CBC), ultrasound or computed tomography and excisional biopsy; fine needle aspiration may not be adequate for diagnosis of certain malignancies, especially hematologic malignancies such as lymphoma, because analysis of the lymph node structure is necessary
    • if presenting with head or neck mass, assessment of risk of malignancy and additional testing considerations may be required
  • In patients suspected of having an infection, review potential epidemiologic clues such as animal exposure, travel, and sick contacts. Acid-fast bacilllus and fungal causes should be considered based on risk factors including geography. Testing may include CBC and disease-specific testing such as cultures and nucleic acid and serologic assays.
  • In patients suspected of having autoimmune disorder, testing may include CBC, additional blood tests to confirm autoimmune disorder such as antinuclear antibody test, anti-double-stranded DNA test, and rheumatoid factor assessment.
  • In patients with unclear etiology despite thorough history and physical exam and initial testing and lymphadenopathy persist > 1-2 weeks:
    • Consider rare or miscellaneous cause.
    • If there is a suggestive cause, specific testing for the suspected cause should be performed or consider empiric treatment.
    • If there is no general indication for etiology:
      • for generalized lymphadenopathy, additional testing should be performed after assessing likelihood of malignancy. Additional testing may include CBC with manual differential, testing for infectious and autoimmune causes, and biopsy.
      • for localized lymphadenopathy, re-evaluate after 1 month.
        • If lymphadenopathy persists, biopsy should be performed.
        • If lymphadenopathy has resolved, continue monitoring to assure no changes or recurrence.

Management

• If underlying cause has been identified, treat condition if option exists, and monitor for changes or persistent lymphadenopathy.
• If treatment options do not exist and benign or self-limited etiology is suspected, provide reassurance and patient education.
• Empiric treatment of patient with lymphadenopathy prior to diagnosis or of unknown causes is not recommended, particularly use of antibiotics or corticosteroids. Corticosteroids should not be initiated in patients without definitive diagnosis as these may cause delay in diagnosis of leukemia or lymphoma because corticosteroids can interfere with nodal biopsy sample evaluation.