Lymphadenopathy

Aka: Lymphadenopathy, Lymphadenitis, Unexplained Lymphadenopathy

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II. Epidemiology

  1. Incidence of Unexplained Lymphadenopathy in primary care: 0.6%
  2. Cancer risk in unexplained adenopathy (primary care)
    1. Age over 40 years: 4% cancer risk
    2. Age under 40 years: 0.4% 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. Classifications
    1. Localized 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. See Generalized Lymphadenopathy
  4. See Lymphadenopathy of the Head and Neck
  5. See Regional Lymphadenopathy
  6. See Hilar Adenopathy

V. Anatomy

  1. See Lymphatic Anatomy
  2. See Regional Lymphadenopathy

VI. History: Exposures

  1. See Medication Causes of Lymphadenopathy
  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. Intravenous Drug Abuse
  6. Blood Transfusion history
  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)

VII. 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

VIII. 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. Lymphadenopathy associated with fever, Night Sweats, weight loss, Hepatomegaly or Splenomegaly

IX. 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 and weight loss
    2. Splenomegaly, Hepatomegaly or Bruising
    3. 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

X. Signs

  1. Abnormal Lymph Node size criteria
    1. Epitrochlear, popliteal or iliac Lymphadenopathy >0.5 cm
    2. Inguinal Lymphadenopathy >1.5 cm
    3. Isolated Lymphadenopathy in children >1.5 to 2.0 cm
    4. Other Lymphadenopathy >1.0 cm
  2. Tenderness to palpation
    1. Does not differentiate benign from malignant nodes
  3. Lymph Node consistency
    1. Rock-hard nodes: Metastatic cancer
    2. Firm-Rubbery nodes: Lymphoma
    3. Soft nodes: Inflammation or infection
    4. Shotty nodes (multiple small buckshot size): Viral
  4. Matted Nodes (connected nodes)
    1. Benign causes
      1. Tuberculosis
      2. Sarcoidosis
      3. Lymphogranuloma venereum
    2. Malignant causes
      1. Metastatic cancer
      2. Lymphoma
  5. 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)
  6. 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

XI. 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)
  4. Management
    1. Consider Antibiotics for persistent acute anterior cervical Lymphadenitis with systemic symptoms in children
    2. Empiric options should target Staph aureus and Group A Streptococcus (Cephalosporins, Augmentin, Clindamycin)
    3. Avoid Corticosteroids until definitive diagnosis made (may mask Lymphoma or Leukemia diagnosis)

XII. Evaluation: Second-line Tests

  1. Indications
    1. Specific indications and normal initial tests
    2. Persistent Generalized Lymphadenopathy
  2. Tests
    1. Tuberculin Skin Test (Purified Protein Derivative)
    2. Rapid Plasma Reagin (RPR)
    3. Antinuclear Antibody (ANA)
    4. Hepatitis B Serology (HBsAg)
    5. HIV Test
  3. Imaging
    1. Chest XRay
    2. Head and neck imaging (as indicated)
      1. Ultrasound is preferred in children <14 years old
      2. MRI or CT of the neck

XIII. Evaluation: Third-line Tests (Biopsy)

  1. Indications
    1. Persistent Lymphadenopathy for more than 3-4 weeks
    2. Malignancy or serious disease suspected
  2. Biopsy: Lymph Node biopsy of most abnormal or largest node
    1. Fine needle aspirate (FNA)
      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
    3. Excisional Biopsy preferred over FNA or needle biopsy if Lymphoma suspected
  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%)

XIV. 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. Ferrer (1998) Am Fam Physician 58(6): 1313-2 [PubMed]
  5. Gaddey (2016) Am Fam Physician 94(11): 896-903 [PubMed]
  6. Habermann (2000) Mayo Clin Proc 75:728 [PubMed]
  7. Libman (1987) J Gen Intern Med 2(1):48-58 [PubMed]
  8. Meier (2014) Am Fam Physician 89(5): 353-8 [PubMed]

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Related Studies

Ontology: Lymphadenitis (C0024205)

Definition (MSHCZE) Zánět mízní uzliny, obv. při bakteriálních zánětech v oblasti, z níž lymfa odtéká do příslušné uzliny. Postižená uzlina je zduřelá, bolestivá. Např. při angíně nebo zánětlivém postižení zubu dojde k l. na krku. Zduření uzliny v třísle provází první stadium syfilis (tvrdý vřed). Zvláštním případem jsou záněty uzlin způsobené tuberkulózou – tzv. specifické lymfadenitidy, jejichž obsah se může provalit a vést k šíření zánětu. Celkové zvětšení uzlin může být i u některých viróz (infekční mononukleóza, zarděnky). (cit. Velký lékařský slovník online, 2013 http://lekarske.slovniky.cz/ )
Definition (NCI) An acute or chronic infectious process affecting the lymph nodes.
Definition (NCI_CTCAE) A disorder characterized by an infectious process involving the lymph nodes.
Definition (MSH) Inflammation of the lymph nodes.
Concepts Disease or Syndrome (T047)
MSH D008199
ICD10 I88.9 , I88.1
SnomedCT 287688007, 274737001, 154838000, 19471005
English Lymphadenitides, Lymphadenitis, LYMPHADENITIS, Lymphadenitis NOS, Lymphadenitis [Disease/Finding], lymph gland infection, glands infection lymph, gland infection lymph, Infection;lymph glands, lymph node inflammation, lymph glands infection, glands infections lymph, Lymph gland infection, Lymphadenitis NOS (disorder), Inflammation of lymph node (finding), Lymph node inflamed, lymphadenitis (diagnosis), Adenitis, Inflammation of lymph node, Lymphadenitis (disorder), lymphadenitis, infection; lymph gland, inflammation; lymph node, lymph gland; infection, lymph node; inflammation, Adenitis, NOS, Lymphadenitis, NOS, adenitis
French ADENITE, Lymphadénite SAI, Infection de ganglion lymphatique, Lymphadénite
Portuguese LINFADENITE, Linfadenite NE, Infecção da glândula linfática, Linfadenite
Spanish LINFADENITIS, Linfadenitis NEOM, linfadenitis, SAI, linfadenitis, SAI (trastorno), Lymphadenitis NOS, adenitis, linfadenitis (trastorno), linfadenitis, Infección de glándula linfática, Linfadenitis
German LYMPHADENITIS, Lymphadenitis NNB, Lymphdrueseninfektion, Lymphadenitis
Italian Infezione linfonodale, Linfadenite, Linfadenite NAS, Linfoadenite
Dutch lymfadenitis NAO, infectie; lymfeklier, lymfeklier; infectie, lymfeklier; ontsteking, ontsteking; lymfeklier, lymfadenitis, lymfeklierinfectie, Adenitis, lymf-, Lymfadenitis
Japanese リンパ節炎ＮＯＳ, リンパ節炎, ﾘﾝﾊﾟｾﾂｴﾝNOS, ﾘﾝﾊﾟｾﾂｴﾝ, リンパ節感染, ﾘﾝﾊﾟｾﾂｶﾝｾﾝ
Swedish Lymfkörtelinflammation
Czech lymfadenitida, Lymfadenitida NOS, Lymfadenitida, Infekce mízní uzliny, zánět mízní uzliny, zánět mízních uzlin
Finnish Imusolmuketulehdus
Russian LIMFADENIT, ADENIT, АДЕНИТ, ЛИМФАДЕНИТ
Croatian LIMFADENITIS
Polish Zapalenie węzłów limfatycznych
Hungarian lymphadenitis, nyirokcsomó fertőzés, lymphadenitis k.m.n.
Norwegian Lymfeknutebetennelse, Lymfadenitt
Derived from the NIH UMLS (Unified Medical Language System)

Ontology: Lymphatic Diseases (C0024228)

Definition (MEDLINEPLUS)

The lymphatic system is a network of tissues and organs. It is made up of

  • Lymph - a fluid that contains white blood cells that defend against germs
  • Lymph vessels - vessels that carry lymph throughout your body. They are different from blood vessels.
  • Lymph nodes - glands found throughout the lymph vessels. Along with your spleen, these nodes are where white blood cells fight infection.

Your bone marrow and thymus produce the cells in lymph. They are part of the system, too.

The lymphatic system clears away infection and keeps your body fluids in balance. If it's not working properly, fluid builds in your tissues and causes swelling, called lymphedema. Other lymphatic system problems can include infections, blockage, and cancer.
Definition (CSP) condition in which there is a deviation from or interruption of the normal structure or function of the lymph or lymph vessels.
Definition (MSH) Diseases of LYMPH; LYMPH NODES; or LYMPHATIC VESSELS.
Concepts Disease or Syndrome (T047)
MSH D008206
SnomedCT 111590001, 155452000, 266326002, 3305006, 234087005, 362971004
English Diseases, Lymphatic, Lymphatic Disease, Lymphatic Diseases, lymphatic disorder, Disease, Lymphatic, Disord of lymph node+lymphat, LYMPHATIC DIS, Disease of lymphoid system, Lymphangiopathy NOS, Lymphatic Diseases [Disease/Finding], disorder of lymphatic system, disorders lymphatic system, Diseases of lymph node or lymph vessels, lymphatic disease, lymphatic diseases, lymphatic disorders, lymphatic system disorder, Lymphangiopathies, Lymphatic disorder, Lymphatic disease, Lymphatics--Diseases, disorder of lymphatic system (diagnosis), Lymphangiopathy, Disorders of lymph node and lymphatics, Disorder of lymphatic system (disorder), Disorder of lymphatic system, Disorders of lymph node and lymphatics (disorder), disease (or disorder); lymphatic, Disorder of lymphatics, NOS, Lymphangiopathy, NOS, Disease of lymphoid system (disorder), Disorder of lymphatics, Disorder of lymphoid system (disorder), Disorder of lymphoid system, Lymphatic Disorders
Italian Linfangiopatia, Linfangiopatie, Patologia linfatica, Linfangiopatia NAS, Malattie linfatiche
Dutch lymfangiopathie NAO, aandoening; lymfatisch, lymfangiopathie, lymfe-angiopathieën, lymfeaandoening, Aandoening, lymfe-, Aandoeningen, lymfe-, Lymfadenopathie, Lymfeaandoening, Lymfeaandoeningen
French Lymphangiopathie SAI, Lymphangiopathies, Lymphangiopathie, Trouble lymphatique, Maladies lymphatiques, Lymphopathies, Maladies du système lymphatique
German Lymphangiopathie NNB, Lymphangiopathien, Lymphangiopathie, Lympherkrankungen, Lymphatische Krankheiten
Portuguese Linfangiopatia NE, Estado Linfático, Linfagiopatias, Afecção linfática, Linfangiopatia, Doenças Linfáticas
Spanish Linfangiopatía NEOM, enfermedad del sistema linfático (trastorno), linfangiopatía, enfermedad de los tejidos linfáticos (trastorno), enfermedad de los tejidos linfáticos, trastorno del sistema linfático (trastorno), trastorno del sistema linfático, trastornos de los ganglios linfáticos (trastorno), trastornos de los ganglios linfáticos, Linfangiopatías, Linfangiopatía, Trastorno linfático, trastorno del sistema linfoide (trastorno), trastorno del sistema linfoide, enfermedad del sistema linfático, Enfermedades Linfáticas
Japanese リンパ管障害, リンパ管障害ＮＯＳ, リンパ管症, リンパ系障害, ﾘﾝﾊﾟｹｲｼｮｳｶﾞｲ, ﾘﾝﾊﾟｶﾝｼｮｳｶﾞｲNOS, ﾘﾝﾊﾟｶﾝｼｮｳ, ﾘﾝﾊﾟｶﾝｼｮｳｶﾞｲ
Swedish Lymfatiska sjukdomar
Czech lymfatické nemoci, Lymfangiopatie, Lymfangiopatie NOS, Onemocnění lymfatických cév, Lymfatická porucha
Finnish Imukudosjärjestelmän sairaudet
Russian LIMFADENOPATIIA, LIMFATICHESKOI SISTEMY BOLEZNI, RETIKULEZ, РЕТИКУЛЕЗ, РЕТИКУЛОЭНДОТЕЛИОЗ, RETIKULOENDOTELIOZ, ЛИМФАДЕНОПАТИЯ, ЛИМФАТИЧЕСКОЙ СИСТЕМЫ БОЛЕЗНИ
Croatian LIMFATIČNE BOLESTI
Polish Choroby układu limfatycznego, Siatkowico-śródbłonkowica, Choroby układu chłonnego
Hungarian lymphatikus betegség, Lymphangiopathiak, Lymphangiopathia k.m.n., Lymphangiopathia
Norwegian Lymfatiske sykdommer, Lymfesykdommer
Derived from the NIH UMLS (Unified Medical Language System)

Related Topics in Lymphatic Disorders

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