II. Epidemiology
- Incidence of Unexplained Lymphadenopathy in primary care: 0.6%
- Cancer risk in unexplained adenopathy (primary care)
- Age over 40 years: 4% cancer risk
- Age under 40 years: 0.4% cancer risk
III. Definitions
- Lymphadenopathy
- Lymph Nodes with abnormal size
- Lymph Nodes with abnormal consistency
- Lymph Nodes of abnormal number
- Classifications
- Localized Lymphadenopathy
- Limited to one area of involvement
- Generalized Lymphadenopathy
- Two or more non-contiguous areas
- Localized Lymphadenopathy
IV. Causes
V. Anatomy
VI. History: Exposures
- See Medication Causes of Lymphadenopathy
- Animal Exposures
- Cat Exposure (Cat Scratch Disease or Toxoplasmosis)
- Ingestion of undercooked meat (Toxoplasmosis, Brucellosis, Anthrax)
- Rabbit, sheep or cattle wool, hair or hide (Anthrax, Brucellosis, Tularemia)
- Rodents and associated fleas (Bubonic Plague)
- Tick Bite (Lyme Disease or Tularemia)
- Tuberculosis exposure
- Intravenous Drug Abuse
- Blood Transfusion history
- Sexually Transmitted Disease exposure
- Occupational or hobby exposure
- Hunters or Trappers (Tularemia)
- Fish handlers (Erysipeloid)
- Mining, masonry or metal work (Beryllium or Silicon exposure)
VII. History: Travel
- See Lymphadenopathy in the Febrile Returning Traveler
- Travel to Southwestern United States
- Travel to Southeastern or central United States
- Travel to Southeast Asia and Australia
- Travel to central or west Africa
- African Trypanosomiasis (African Sleeping Sickness)
- Travel to central or south America
- American Trypanosomiasis (Chagas' Disease)
- Travel East Africa, China, Latin America, Mediterranean
- Kala-azar (Leishmaniasis)
- Travel to Mexico, Peru, Chile, Pakistan, Egypt, Indonesia
VIII. Risk Factors: Malignant cause of Lymphadenopathy
- Age >40 years old
- Lymphadenopathy >4-6 weeks (esp if not returned to baseline by 8-12 weeks)
- Generalized Lymphadenopathy (at least 2 regions involved)
- Male gender
- White race
- Supraclavicular Lymphadenopathy
- Lymphadenopathy associated with fever, Night Sweats, weight loss, Hepatomegaly or Splenomegaly
IX. Symptoms
- Isolated Lymphadenopathy <2 weeks or >12 months without change
- Malignancy unlikely
- Exception: Low grade or indolent Lymphoma (which have associated systemic symptoms)
- Symptoms associated with malignancy (e.g. Leukemia, Lymphoma, solid malignancy metastases)
- Fever, Night Sweats and weight loss
- Splenomegaly, Hepatomegaly or Bruising
- Lymphadenopathy >5mm supraclavicular, popliteal or iliac
- Symptoms associated with Connective Tissue Disease (e.g. RA, SLE, Sjogren Syndrome, Dermatomyositis)
- Fever, chills
- Arthralgias and myalgias
- Rash
- Joint Stiffness
X. Signs
- Abnormal Lymph Node size criteria
- Epitrochlear, popliteal or iliac Lymphadenopathy >0.5 cm
- Inguinal Lymphadenopathy >1.5 cm
- Isolated Lymphadenopathy in children >1.5 to 2.0 cm
- Other Lymphadenopathy >1.0 cm
- Tenderness to palpation
- Does not differentiate benign from malignant nodes
- Lymph Node consistency
- Matted Nodes (connected nodes)
- Benign causes
- Malignant causes
- Metastatic cancer
- Lymphoma
-
Splenomegaly
- Infectious Mononucleosis
- Hodgkin's Disease
- Non-Hodgkin's Lymphoma
- Chronic Lymphocytic Leukemia
- Acute Leukemia
- Rarely associated with metastatic cancer
XI. Evaluation: Initial Tests
- Evaluation should be directed at region of primary Lymphadenopathy
- Specific regional approaches are preferred over more broad, shotgun approaches
- See Neck Masses in Children
- See Neck Masses in Adults
- Indications
- Specific indications based on location and exposures
- Generalized Lymphadenopathy
- Tests
- Complete Blood Count with manual differential
- Monospot (MononucleosisSerology)
- Management
- Consider Antibiotics for persistent acute anterior cervical Lymphadenitis with systemic symptoms in children
- Empiric options should target Staph aureus and Group A Streptococcus (Cephalosporins, Augmentin, Clindamycin)
- Avoid Corticosteroids until definitive diagnosis made (may mask Lymphoma or Leukemia diagnosis)
XII. Evaluation: Second-line Tests
- Indications
- Specific indications and normal initial tests
- Persistent Generalized Lymphadenopathy
- Tests
- Imaging
- Chest XRay
- Head and neck imaging (as indicated)
- Ultrasound is preferred in children <14 years old
- MRI or CT of the neck
XIII. Evaluation: Third-line Tests (Biopsy)
- Indications
- Persistent Lymphadenopathy for more than 3-4 weeks
- Malignancy or serious disease suspected
- Biopsy: Lymph Node biopsy of most abnormal or largest node
- Fine needle aspirate (FNA)
- Fast, accurate, minimally invasive and safe
- High accuracy except where Lymph Node architecture needs to be defined (e.g. Lymphoma)
- Lioe (1999) Cytopathology 10(5): 291-7 [PubMed]
- Core needle biopsy
- Excisional Biopsy preferred over FNA or needle biopsy if Lymphoma suspected
- Fine needle aspirate (FNA)
- Efficacy
- Highest yield site: Supraclavicular nodes
- Lowest yield site: Inguinal nodes
- Most common findings on biopsy
- Abnormal but non-specific findings (40%)
- Metastatic cancer (25%)
- Intrinsic malignancy such as Lymphoma (20%)
- Tuberculosis (10%)
XIV. References
- Dornbland (1992) Adult Ambulatory Care, p. 662-7
- Lee (1999) Wintrobe's Hematology, p. 1826-30
- Wilson (1991) Harrison's Internal Medicine, p. 354-6
- Ferrer (1998) Am Fam Physician 58(6): 1313-2 [PubMed]
- Gaddey (2016) Am Fam Physician 94(11): 896-903 [PubMed]
- Habermann (2000) Mayo Clin Proc 75:728 [PubMed]
- Libman (1987) J Gen Intern Med 2(1):48-58 [PubMed]
- Meier (2014) Am Fam Physician 89(5): 353-8 [PubMed]