| |

Lymphadenopathy: History Taking and Differential Diagnoses

Last updated:

History of Presenting Complaint

Overview

With each symptom, always (if relevant) ask about:

  • When did it start?
  • Did it come on suddenly or gradually?
  • Is it continuous or intermittent?
  • Has this ever happened before?

Lymphadenopathy

  • Site:
    • Where are the lumps?
    • Are they on both sides?
  • Onset:
    • When did the lumps start?
    • Was there any preceding illness?
  • Character:
    • Do the lumps hurt?
      • Does drinking alcohol elicit pain?
    • Are the lumps warm?
    • Are the lumps red?
  • Associated symptoms:
    • See review of systems below
  • Timeline:
    • Have the lumps changed over time?
      • Have they grown?
      • Have new ones emerged?
      • Lumps lasting >6 weeks are more likely to be malignant
  • Severity:
    • How big are the lumps?

Review of systems

  • Screen for red flags for haematological malignancy:
    • Fever, night sweats, unexplained weight loss
    • Unexplained bruising or bleeding
    • Bone pain
    • Recurrent, severe, persistent, or unusual infections
  • Screen for red flags for head and neck cancers:
  • Screen for infection:
    • Sore throat, red eye, ulcers, dysuria, genital discharge, fever
    • Recent foreign travel, insect/animal bites
    • Are contacts also ill?
  • Screen for autoimmune disorders:

Past Medical History

Questions include:

  • Do they have any other medical conditions?
  • Have they ever had any previous surgery?
  • Do they take any regular medications?
  • Do they take any over-the-counter medications, herbal remedies, or supplements?

Family History

  • Is there any family history of anything similar?

Allergy History

  • Are they allergic to anything?
    • What happens during the allergic reaction?

Social History

  • Do they smoke?
    • If so, how much and how long?
  • Do they drink alcohol?
    • If so, how much and how long?
  • Do they use any illicit drugs?
    • If so, how much and how long?
  • What is their occupation?
  • Who’s at home?
    • What support do they have?
  • How has this impacted their activities of daily living?
  • Has there been any recent foreign travel?

Physical Examinations

Overview

A reticuloendothelial examination is performed. The following properties of lymph nodes should be assessed:

  • Size:
    • Abnormal lymph nodes are generally >1 cm in diameter
    • Persistent lymph nodes >6 weeks may suggest an underlying malignancy
  • Shape and consistency:
    • In general, hard, firm, and irregular nodes suggest malignancy
    • Tender nodes suggest infection or inflammation
    • Overlying skin changes (such as ulcers) may suggest malignancy
    • Pulsatile lumps suggest a vascular cause
  • Mobility:
    • Normal lymph nodes are mobile and freely moveable
    • Lymph nodes that are fixed or tethered to adjacent or underlying structures suggest malignancy
  • Distribution:
    • Is the lymphadenopathy localised (in one region) or generalised (in multiple regions)?
    • Generalised lymphadenopathy suggests systemic inflammation
  • Location:
    • Cervical lymphadenopathy – drains the head and neck:
      • Causes include infection (e.g. pharyngitis, infectious mononucleosis, and tuberculosis) or malignancy (such as laryngeal cancers or lymphoma)
    • Supraclavicular lymphadenopathy – drains the lungs, gastrointestinal tract, and genitourinary tract:
      • Supraclavicular lymphadenopathy is much more suggestive of malignancy
      • Causes include lymphoma, lung cancer, breast cancer, gastric cancer
    • Axillary lymphadenopathy – drains the upper limb, breast, and thorax
      • Causes include breast cancer, melanoma, skin infections
    • Inguinal lymphadenopathy – drains the lower abdomen, lower limb, external genitalia, and lower extremities:
      • Causes include cellulitis, sexually-transmitted infections, lymphoma, melanoma, genitourinary cancer
    • Hilar lymphadenopathy:
    • Other lymphadenopathies:
      • Sister Mary Joseph’s nodes – suggest gastric cancer

Investigations

Overview

When suggesting investigations in an OSCE, the BOXES (Blood tests, orifice tests, x-rays, ECGs, special tests) mnemonic is useful for deciding the order of investigations:

  • Blood tests:
    • Full blood count (FBC) and white cell differential:
      • May identify blood dyscrasias
    • Throat culture:
      • To screen for infection
    • Monospot test:
      • To screen for infectious mononucleosis
    • HIV test:
      • To screen for HIV
  • Orifice tests:
    • Sputum culture:
      • For tuberculosis
  • X-rays:
    • Chest X-ray:
      • To assess hilar lymph nodes and screen for chest pathology (e.g. lung cancer)
  • Special tests:
    • Ultrasound scan:
      • Malignant lymph nodes may appear differently (e.g. they may have necrosis, calcification etc.)
    • Lymph node biopsy:
      • Diagnostic for lymphoma
    • Bone marrow biopsy:
      • For other haematological malignancies

Differential Diagnoses: Infective

Infectious mononucleosis

  • A history and physical exam may reveal:
    • A triad of fever, pharyngitis, and lymphadenopathy
    • Splenomegaly may be present
    • Lymphadenopathy is in the anterior and posterior triangles of the neck
    • Many patients have severe fatigue
  • Investigations may reveal:
    • Full blood count (FBC):
      • May show lymphocytosis
    • Monospot:
      • Positive

Reactive lymphadenopathy

  • A history and physical exam may reveal:
    • Fever, malaise, myalgia
    • Sore throat, cough
    • Coryza, gastroenteritis, rash
    • Lymphadenopathy may be tender and warm, which may suggest the development of an abscess
  • Investigations depend on the underlying cause

HIV

  • A history and physical exam may reveal:
    • Flu-like symptoms including fever, malaise, myalgia
    • A history of exposure to high-risk material such as needlestick injuries, intravenous drug use, unprotected sexual intercourse
  • Investigations may reveal:
    • HIV p24 antigen and HIV antibody:
      • Positive

Hepatitis B and C

  • A history and physical exam may reveal:
    • A history of exposure to high-risk material such as needlestick injuries, intravenous drug use, unprotected sexual intercourse
    • Hepatomegaly, jaundice
  • Investigations may reveal:

Tuberculosis

  • A history may reveal:
    • Cough, fever, weight loss, night sweats, haemoptysis
    • HIV/immunosuppression
    • Travel to an endemic area
  • A physical exam may reveal:
    • Fever, tachypnoea
    • Lymphadenopathy tends to affect the cervical lymph nodes
  • Investigations may reveal:
    • Chest x-ray:
      • May show bilateral hilar lymphadenopathy, may show upper lobe cavitation
    • Sputum culture:
      • Diagnostic

Measles

  • A history may reveal:
    • A prodromal fever followed by conjunctivitis, cough, and a rash starting on the head or trunk, then spreading 
  • A physical exam may reveal:
    • Lymphadenopathy tends to be generalised
    • Koplik’s spots
    • A maculopapular rash
  • Investigations may reveal:
    • Measles-specific IgM and/or IgG:
      • Positive

Mumps

  • A history may reveal:
    • Fever, sore throat, and parotitis (enlarged painful salivary glands)
  • A physical exam may reveal:
    • Parotitis
    • Lymphadenopathy tends to be cervical or occipital
  • Diagnosis is generally clinical

Rubella

  • A history may reveal:
    • Prodromal fever followed by a maculopapular rash starting on the face before spreading to the whole body
  • A physical exam may reveal:
    • Maculopapular rash
    • Lymphadenopathy tends to be post-auricular and suboccipital
  • Investigations may reveal:
    • Anti-rubella IgM and/or IgG:
      • Positive

Cat scratch disease

  • A history and physical exam may reveal:
    • Exposure to cat scratches
    • Cuts and scratches on the skin
    • Lymphadenopathy tends to be axillary
  • Investigations may reveal:
    • Bartonella henselae serology:
      • Positive

Toxoplasmosis

  • A history may reveal:
    • Exposure to cats, ingestion of undercooked meat, exposure to soil
    • Fever, malaise, pharyngitis
    • A history of immunosuppression
  • A physical exam may reveal:
    • Lymphadenopathy tends to be cervical and non-tender
  • Investigations may reveal:
    • Toxoplasma serology tests:
      • Positive

Genital herpes

  • A history and physical exam may reveal:
    • Painful genital ulceration, dysuria, and pruritus
    • Unprotected sexual intercourse
    • Inguinal lymphadenopathy
  • Investigations may reveal:
    • Nucleic acid amplification tests (NAAT):
      • Positive

Lymphogranuloma venereum

  • A history and physical exam may reveal:
    • Genital ulcers
    • Painful inguinal lymphadenopathy
    • Unprotected sexual intercourse
    • A history of HIV
  • Investigations may reveal:
    • Nucleic acid amplification tests (NAAT):
      • Positive

Chancroid

  • A history and physical exam may reveal:
    • Painful genital ulcers that have ragged borders 
    • A history of unprotected sexual intercourse
    • Unilateral or bilateral inguinal lymphadenopathy
  • Investigations may reveal:
    • Haemophilus ducreyi serology and polymerase chain reaction:
      • Positive

Syphilis

  • A history and physical exam may reveal:
    • A painless ulcer at the site of sexual contact
    • Generalised lymphadenopathy – usually seen in secondary syphilis
    • Fever, diffuse rash on the palms and soles
    • Gummas, Argyll-Robertson pupil
  • Investigations may reveal:
    • Venereal Disease Research Laboratory (VDRL) and rapid plasma reagin (RPR):
      • Positive

Differential Diagnoses: Malignant

Lymphoma

  • A history may reveal:
    • Non-tender supraclavicular/rubbery lymphadenopathy
    • B-symptoms – fevers, night sweats, weight loss
    • Pruritus
  • A physical exam may reveal:
    • Lymphadenopathy
    • Splenomegaly/hepatomegaly
  • Investigations may reveal:
    • Full blood count (FBC) and white cell differential:
      • Haemoglobin: may be low due to bone marrow involvement
      • White cell count: high or low – depending on bone marrow involvement
      • Platelets: low – due to bone marrow involvement
    • Erythrocyte sedimentation rate (ESR):
      • May be elevated
    • Chest x-ray:
      • May show mediastinal mass
    • Immunophenotyping:
      • Can differentiate HL and NHL using flow cytometry– HL is usually CD30 positive and CD15 positive
    • Lymph node biopsy:
      • Shows Reed-Sternberg cells in Hodgkin’s lymphoma – these are cells that are either nucleated or have a bilobed nucleus with eosinophilic inclusion-like nucleoli. They have an ‘owl’s eye’ appearance

Metastatic malignancy

  • A history may reveal:
    • New lymphadenopathy in a patient with cancer should raise suspicion of metastasis
    • There may be constitutional symptoms and other features of the specific cancer (e.g. skin lesions, shortness of breath and similar pulmonary symptoms, breast lumps etc.)

Differential Diagnoses: Autoimmune/Inflammatory

Rheumatoid arthritis

  • A history and physical exam may reveal:
    • Inflammatory pain and stiffness:
      • Pain and stiffness improve on exertion
      • Morning stiffness >30 minutes – 1 hour
    • Joint deformities may be seen:
      • Swan neck deformity
      • Boutonnière’s deformity
    • Bilateral distal polyarthropathy
    • Features of systemic upset may be seen
    • Joints affected include MCPs and PIPs, but any can be affected
    • Lymphadenopathy is often in the axillary region
  • Investigations may reveal:
    • Rheumatoid factor (RF):
      • Positive
    • Anti-cyclic citrullinated peptide (anti-CCP) antibodies:
      • Positive

Systemic lupus erythematosus

  • A history and physical exam may reveal:
    • Classically affects young women
    • Photosensitive rash may be present
    • Such as the malar ‘butterfly-shaped’ rash on the face sparing the nasolabial folds
    • Generalised myalgia
    • Mouth ulcers
    • Pleurisy
    • Hair loss
    • Lymphadenopathy may be generalised
  • Investigations may reveal:
    • Anti-nuclear antibodies (ANA):
      • Positive
    • Anti-double-stranded DNA (anti-dsDNA):
      • Positive

Sjogren’s syndrome

  • A history may reveal:
    • Dry eyes, dry mouth, and vaginal dryness are predominant features
    • Arthralgia
    • Increased risk of lymphoma, lymphadenopathy may suggest its development
  • Investigations may reveal:
    • Anti-Ro and anti-La antibodies:
      • Positive
      • These backward spells (ORAL)

Sarcoidosis

  • A history may reveal:
    • Fever, arthritis, erythema nodosum, weight loss, malaise
  • A physical exam may reveal:
  • Investigations may reveal:
    • Chest x-ray:
      • Bilateral hilar lymphadenopathy
    • Serum ACE:
      • Elevated
    • Serum calcium:
      • Elevated
    • Lung biopsy:
      • Non-caseating granuloma:

Kawasaki disease

  • A history may reveal:
    • Mainly seen in children
    • Prolonged fever that is resistant to antipyretics, irritability 
  • A physical exam may reveal:
    • Cervical lymphadenopathy
    • Red rash on the palms and soles which may peel
    • Bright red and cracked lips
    • Conjunctival redness
    • Strawberry tongue
  • Investigations may reveal:
    • Diagnosis is clinical although ESR and CRP may be elevated and echocardiography is performed in all patients to screen for coronary artery aneurysms

Author