Causes

• Infection:
  • Regional lymphadenopathy draining primary infection:
    • Viral: adenovirus, mumps, enterovirus, arbovirus, rubella, herpes simplex virus, infectious mononucleosis
    • Bacterial: staphylococcal and streptococcal infection, tuberculosis (TB), cat scratch disease, brucellosis, plague, filariasis, tularaemia, syphilis, melioidosis, glanders, lymphogranuloma venereum (chlamydia), chancroid, scrub typhus
    • Fungal: blastomycosis, coccidioidomycosis
    • Protozoal: trypanosomiasis, cutaneous leishmaniasis
  • Generalised lymphadenopathy: many of the infections above show a predisposition to certain sites but may also cause generalised lymphadenopathy, particularly secondary syphilis. Others causes include:
    • Viral, eg HIV, cytomegalovirus (CMV), hepatitis B, mumps, measles, dengue fever (arbovirus)
    • Bacterial, eg TB, typhoid fever, septicaemia
    • Protozoal, eg toxoplasmosis, visceral leishmaniasis
• Primary haematological causes:
  • Leukaemia
  • Hodgkin's disease and non-Hodgkin's lymphoma (including mycosis fungoides)
  • Myeloproliferative disorders, (including polycythaemia rubra vera)
• Regional lymphadenopathy draining local malignancy
• Granulomatous lymphadenopathy, eg TB, leprosy, atypical mycobacteria, Crohn's disease, Wegener's granulomatosis
• Other causes include sarcoidosis, systemic lupus erythematosus (SLE), rheumatoid arthritis, dermatomyositis, Sjögren's syndrome, and drug reactions (eg penicillins, allopurinol, captopril, carbamazepine)

Presentation

Careful reappraisal of the history and full examination are required, determining the size and character of the node(s). In the absence of obvious infection or any other underlying disorder, or if there is any suspicion of malignancy - refer.

• Localised lymphadenopathy should prompt a search for an adjacent precipitating lesion and an examination of other nodal areas to rule out generalised lymphadenopathy.^[3]
• Lymph nodes greater than 1 cm in diameter are generally considered to be abnormal.^[1]
• History of malaise and weight loss may be associated with malignancy or certain infections, eg HIV, TB.
• Painful, tender lymph nodes are usually associated with infection.
• Firm or hard, painless nodes are often associated with malignancy.
• Full examination is essential and may reveal associated bruising (eg leukaemia) or hepatosplenomegaly (eg lymphoma).
• Lymphadenopathy in the neck may cause superior vena cava obstruction.

Differential diagnosis

• Subcutaneous lesions, eg lipoma, abscess
• Hernia
• Skin lesions, eg sebaceous cyst
• Neck (see separate article Neck Lumps and Bumps): branchial cleft cysts, cystic hygromas, salivary glands, thyroglossal duct cysts (usually in midline)

Investigations

These will be governed by the history and examination and likely cause of lymphadenopathy. Investigations may not be required in cases of obvious cause and quick resolution with or without treatment.

• Full blood count: white cell count raised in infection or malignancy, blood film for leukaemia
• Acute phase reactants, eg ESR and CRP, often raised in infection or malignancy
• Liver function tests: liver infiltration
• Infection:
  • Swabs from primary infection site for culture and sensitivities
  • Viral titres, eg Epstein-Barr virus, HIV, hepatitis
  • Investigations for TB
  • Syphilis serology
  • Toxoplasma screen
  • Blood cultures
• Autoantibody screen: SLE, rheumatoid arthritis
• Kveim test: sarcoidosis
• Chest X-ray: sarcoidosis, TB, primary or secondary malignancy
• CT scan: nodal distribution, staging of lymphoma
• Fine needle aspiration or biopsy (ideally excisional biopsy) of lymph node may be required; some patients, particularly children, remain undiagnosed after biopsy
• Sentinel node biopsy:
  • The sentinel node is the first node identified or the node with the highest radioactivity count.
  • Sentinel node biopsy can avoid the need for block dissection of lymph nodes. It is often used in the preoperative assessment of breast cancer and melanoma and may have benefits in other cancers.
  • The sentinel node can be identified either by local injection of blue dye and following its path, or by gamma camera imaging following injection of 99mTc.