Lymphadenopathy

Aka: Lymphadenopathy, Lymphadenitis, Unexplained Lymphadenopathy

advertisement

II. Epidemiology

  1. Incidence of Unexplained Lymphadenopathy in primary care: 0.6%
  2. Cancer risk in unexplained adenopathy (primary care)
    1. Overall cancer risk: 1.1%
    2. Age over 40 years: 4% cancer risk

III. Definitions

  1. Lymphadenopathy
    1. Lymph Nodes with abnormal size
    2. Lymph Nodes with abnormal consistency
    3. Lymph Nodes of abnormal number
  2. Lymphadenitis
    1. Infectious or inflammatory Lymph Node swelling (Lymphadenopathy)
    2. Associated with localized pain, tenderness, edema and skin changes
    3. Systemic symptoms such as fever may also be present
  3. Classifications
    1. Localized or Regional Lymphadenopathy
      1. Limited to one area of involvement
    2. Generalized Lymphadenopathy
      1. Two or more non-contiguous areas

IV. Causes

  1. See Medication Causes of Lymphadenopathy
  2. See Lymphadenopathy in the Febrile Returning Traveler
  3. Generalized Lymphadenopathy (25% of causes, typically systemic illness)
    1. See Generalized Lymphadenopathy
  4. Regional Lymphadenopathy
    1. See Lymphadenopathy of the Head and Neck
    2. See Regional Lymphadenopathy
    3. See Hilar Adenopathy
  5. Mnemonic: MIAMI
    1. Malignancy (e.g. Leukemia, Lymphoma, metastases, Skin Cancer)
    2. Infection (e.g. Skin Infections, Viral Infections, Granulomatous diseases, Syphilis, Tuberculosis, Cat Scratch Disease)
    3. Autoimmune Disorders (e.g. Dermatomyositis, RA, SLE, Sarcoidosis)
    4. Miscellaneous or unusual causes (e.g. Kawasaki Disease, PFAPA, Castleman disease)
    5. Iatrogenic (e.g. medications, Vaccines, Serum Sickness)

V. History: Exposures

  1. Symptoms suggestive of acute infection
    1. Fever, chills, malaise
    2. Pharyngitis, cough, congestion
    3. Headache, myalgias
    4. Nausea or Vomiting
  2. Animal Exposures
    1. Cat Exposure (Cat Scratch Disease or Toxoplasmosis)
    2. Ingestion of undercooked meat (Toxoplasmosis, Brucellosis, Anthrax)
    3. Rabbit, sheep or cattle wool, hair or hide (Anthrax, Brucellosis, Tularemia)
    4. Rodents and associated fleas (Bubonic Plague)
  3. Tick Bite (Lyme Disease or Tularemia)
  4. Tuberculosis exposure
  5. Blood Transfusion history
  6. New medications or Vaccinations
    1. See Medication Causes of Lymphadenopathy
  7. Sexually Transmitted Disease exposure
    1. See Lymphadenopathy Causes
    2. HIV Infection
    3. Lymphogranuloma venereum
    4. Syphilis
    5. Chancroid
  8. Occupational or hobby exposure
    1. Hunters or Trappers (Tularemia)
    2. Fish handlers (Erysipeloid)
    3. Mining, masonry or metal work (Beryllium or Silicon exposure)
  9. Autoimmune related symptoms (e.g. RA, SLE, Dermatomyositis, Drug Reaction)
    1. Arthralgias or Joint Stiffness
    2. Muscle Weakness
    3. Fever or chills
  10. Substance Use Disorders (infectious or malignancy risk)
    1. Intravenous Drug Abuse
    2. Alcohol Use Disorder
    3. Tobacco Abuse

VI. History: Travel

  1. See Lymphadenopathy in the Febrile Returning Traveler
  2. Travel to Southwestern United States
    1. Coccidioidomycosis
    2. Bubonic Plague
  3. Travel to Southeastern or central United States
    1. Histoplasmosis
  4. Travel to Southeast Asia and Australia
    1. Scrub Typhus
  5. Travel to central or west Africa
    1. African Trypanosomiasis (African Sleeping Sickness)
  6. Travel to central or south America
    1. American Trypanosomiasis (Chagas' Disease)
  7. Travel East Africa, China, Latin America, Mediterranean
    1. Kala-azar (Leishmaniasis)
  8. Travel to Mexico, Peru, Chile, Pakistan, Egypt, Indonesia
    1. Typhoid Fever

VII. Risk Factors: Malignant Cause of Lymphadenopathy

  1. Age >40 years old
  2. Lymphadenopathy >4-6 weeks (esp if not returned to baseline by 8-12 weeks)
  3. Generalized Lymphadenopathy (at least 2 regions involved)
  4. Male gender
  5. White race
  6. Supraclavicular Lymphadenopathy
  7. B Symptoms (fever, Night Sweats)
  8. Unintentional Weight Loss (esp. >10 lb or 4.5 kg in last 6-12 months)
  9. Hepatomegaly or Splenomegaly

VIII. Symptoms

  1. Isolated Lymphadenopathy <2 weeks or >12 months without change
    1. Malignancy unlikely
    2. Exception: Low grade or indolent Lymphoma (which have associated systemic symptoms)
  2. Symptoms associated with malignancy (e.g. Leukemia, Lymphoma, solid malignancy metastases)
    1. Fever, Night Sweats
    2. Unintentional Weight Loss (esp. >10 lb or 4.5 kg in last 6-12 months)
    3. Splenomegaly, Hepatomegaly or Bruising
    4. Lymphadenopathy >5mm supraclavicular, popliteal or iliac
  3. Symptoms associated with Connective Tissue Disease (e.g. RA, SLE, Sjogren Syndrome, Dermatomyositis)
    1. Fever, chills
    2. Arthralgias and myalgias
    3. Rash
    4. Joint Stiffness

IX. Signs

  1. Anatomy
    1. See Lymphatic Anatomy
    2. See Regional Lymphadenopathy
  2. Abnormal Lymph Node size criteria (normal Lymph Nodes are typically <0.5 to 1 cm)
    1. Epitrochlear, popliteal or iliac Lymphadenopathy >0.5 cm
    2. Inguinal Lymphadenopathy >2 cm
    3. Isolated Lymphadenopathy in children >1.5 to 2.0 cm
    4. Other Lymphadenopathy >1.0 cm
  3. Tenderness to palpation
    1. See Tender Regional Lymphadenopathy
    2. Tenderness does not differentiate benign from malignant nodes
  4. Lymph Node consistency
    1. Rock-hard nodes: Metastatic cancer
    2. Firm-Rubbery nodes: Lymphoma
    3. Soft nodes: Inflammation or infection
    4. Tender, fluctuant, mobile nodes (Lymphadenitis): Bacterial Infections
    5. Shotty nodes (multiple small buckshot size): Viral Infections
  5. Matted or Fixed Nodes (connected nodes)
    1. Benign causes
      1. Tuberculosis
      2. Sarcoidosis
      3. Lymphogranuloma venereum
    2. Malignant causes
      1. Metastatic cancer
      2. Lymphoma
  6. Lymph Node Regions
    1. See Regional Lymphadenopathy
    2. Classic Lymphadenopathy locations associated with malignancy
      1. Left supraclavicular Node (Virchow's Node)
      2. Left Axillary Node (Irish Node)
      3. Periumbilical Node (Sister Mary Joseph Nodule)
  7. Splenomegaly
    1. Infectious Mononucleosis
    2. Hodgkin's Disease
    3. Non-Hodgkin's Lymphoma
    4. Chronic Lymphocytic Leukemia
    5. Acute Leukemia
    6. Rarely associated with metastatic cancer

X. Evaluation: Initial Tests

  1. Evaluation should be directed at region of primary Lymphadenopathy
    1. Specific regional approaches are preferred over more broad, shotgun approaches
    2. See Neck Masses in Children
    3. See Neck Masses in Adults
  2. Indications
    1. Specific indications based on location and exposures
    2. Generalized Lymphadenopathy
  3. Tests
    1. Complete Blood Count with manual differential
    2. Monospot (MononucleosisSerology)
    3. Group A Streptococcal PCR
  4. Management
    1. Avoid Corticosteroids until definitive diagnosis made (may mask Lymphoma or Leukemia diagnosis)
    2. Consider Antibiotics for persistent acute anterior cervical Lymphadenitis with systemic symptoms in children
      1. Indicated in Bacterial Lymphadenitis (unilateral, tender nodes with skin erythema) or nodes >2-3 cm
      2. Empiric first line Antibiotics target MSSA, Group A Streptococcus
        1. Amoxicillin-Clavulanate (Augmentin)
        2. Cephalexin (Keflex)
      3. Empiric MRSA coverage
        1. Trimethoprim-sulfamethoxazole (Bactrim, Septra)
        2. Doxycycline (age >8 years)
        3. Clindamycin (risk of induced resistance)
      4. Suspected Cat Scratch Disease
        1. Azithromycin

XI. Evaluation: Second-line Tests

  1. Indications
    1. Specific indications and normal initial tests
    2. Persistent Generalized Lymphadenopathy >4 weeks
  2. Labs: General
    1. Complete Blood Count with manual differential (if not already performed above)
    2. C-Reactive Protein (cRP)
    3. Erythrocyte Sedimentation Rate (ESR)
    4. Lactate Dehydrogenase (if suspected Lymphoma or Leukemia)
  3. Labs: Autoimmune
    1. Anticyclic Citrullinated Peptide Antibody
    2. Rheumatoid Factor
    3. Antinuclear Antibody (ANA)
    4. Other labs
      1. Complement Levels
      2. dsDNA Antibody
  4. Labs: Infectious
    1. Monospot (if not already performed above)
    2. Epstein Barr VirusSerology
    3. Cytomegalovirus PCR
    4. Tuberculin Skin Test (Purified Protein Derivative) or IFN-Gamma Release Assay (Quantiferon-TB)
    5. Rapid Plasma Reagin (RPR) or other Treponemal Antibody
    6. Chlamydia PCR
    7. Gonorrhea PCR
    8. Hepatitis B Serology (HBsAg)
    9. HIV Test
  5. Imaging
    1. Chest XRay
      1. Mediastinal Widening (Lymphoma, Sarcoidosis)
      2. Mediastinal Lymphadenopathy
      3. Hilar Lymphadenopathy
    2. Head and neck imaging (as indicated)
      1. Ultrasound (preferred in children <14 years old)
      2. CT soft tissue neck (age >14 years old or adults)
    3. Imaging of other regions as indicated
      1. Start with Ultrasound or XRay in age <14 years
      2. Consider CT chest Abdomen and Pelvis with contrast in age >14 years with suspected malignancy

XII. Evaluation: Third-line Tests (Biopsy)

  1. Indications
    1. Persistent Lymphadenopathy for more than 4 weeks with no other cause identified
    2. Malignancy or serious disease suspected
  2. Biopsy: Lymph Node biopsy of most abnormal or largest node
    1. Fine needle aspirate (FNA)
      1. Refer to Interventional Radiology
      2. Preferred if a small needle is needed due to node location
      3. Preferred first-line test for Cervical Lymphadenopathy (followed by Excisional Biopsy)
        1. Fast, accurate, minimally invasive and safe
        2. High accuracy except where Lymph Node architecture needs to be defined (e.g. Lymphoma)
        3. Lioe (1999) Cytopathology 10(5): 291-7 [PubMed]
    2. Core needle biopsy
      1. Refer to Interventional Radiology
      2. Preferred if Lymph Node is clearly visible on imaging and easily accessible
      3. Better initial test than FNA (esp. for Lymphoma)
        1. Maintains tissue architecture (distorted by FNA)
        2. Less prone to sampling error than FNA
        3. May be combined with immunohistochemical and molecular techniques for greater efficacy
    3. Excisional Biopsy
      1. Typically follows positive or indeterminate FNA or core needle biopsy
      2. Refer to surgery
  3. Efficacy
    1. Highest yield site: Supraclavicular nodes
    2. Lowest yield site: Inguinal nodes
  4. Most common findings on biopsy
    1. Abnormal but non-specific findings (40%)
    2. Metastatic cancer (25%)
    3. Intrinsic malignancy such as Lymphoma (20%)
    4. Tuberculosis (10%)

XIII. References

  1. Dornbland (1992) Adult Ambulatory Care, p. 662-7
  2. Lee (1999) Wintrobe's Hematology, p. 1826-30
  3. Wilson (1991) Harrison's Internal Medicine, p. 354-6
  4. Ali (2022) Cureus 14(10): e30623 [PubMed]
  5. Falk (2025) Am Fam Physician 112(3): 286-93 [PubMed]
  6. Ferrer (1998) Am Fam Physician 58(6): 1313-2 [PubMed]
  7. Gaddey (2016) Am Fam Physician 94(11): 896-903 [PubMed]
  8. Habermann (2000) Mayo Clin Proc 75:728 [PubMed]
  9. Libman (1987) J Gen Intern Med 2(1):48-58 [PubMed]
  10. Meier (2014) Am Fam Physician 89(5): 353-8 [PubMed]

Images: Related links to external sites (from Bing)

These images are a random sampling from a Bing search on the term "Lymphadenopathy." Click on the image (or right click) to open the source website in a new browser window. Search Bing for all related images

Related Topics in Lymphatic Disorders

advertisement