Lymph nodes, in conjunction with the spleen, tonsils, adenoids, and Peyer patches, are highly organized centers of immune cells that filter antigen from the extracellular fluid. Directly interior to the fibrous capsule is the subcapsular sinus. This allows lymph, an ultrafiltrate of blood, to traverse from the afferent lymph vessels, through the sinuses, and out the efferent vessels. The sinuses are studded with macrophages, which remove 99% of all delivered antigens.

Interior to the subcapsular sinus is the cortex, which contains primary follicles, secondary follicles, and the interfollicular zone. Follicles within the cortex are major sites of B-cell proliferation, whereas the interfollicular zone is the site of antigen-dependent T-cell differentiation and proliferation. The deepest structure within the lymph node is the medulla, consisting of cords of plasma cells and small B lymphocytes that facilitate immunoglobulin secretion into the exiting lymph.

The lymph node, with its high concentration of lymphocytes and antigen-presenting cells, is an ideal organ for receiving antigens that gain access through the skin or gastrointestinal tract. Nodes have considerable capacity for growth and change. Lymph node size depends on the person's age, the location of the lymph node in the body, and antecedent immunological events. In neonates, lymph nodes are barely perceptible, but a progressive increase in total lymph node mass is observed until later childhood. Lymph node atrophy begins during adolescence and continues through later life.


Lymphadenopathy reflects disease involving the reticuloendothelial system, secondary to an increase in normal lymphocytes and macrophages in response to an antigen. Most lymphadenopathy in children is due to benign self-limited disease such as viral infections. Other less common etiologies responsible for adenopathy include nodal accumulation of inflammatory cells in response to an infection in the node (lymphadenitis), neoplastic lymphocytes or macrophages (lymphoma), or metabolite-laden macrophages in storage diseases (Gaucher disease).



United States

The precise incidence of lymphadenopathy is not known, but estimates of palpable adenopathy in childhood vary from 38-45%,[1] and lymphadenopathy is one of the most common clinical problems encountered in pediatrics.[2] Determining whether adenopathy is simply a normal response to frequent viral infections within an age group or if it is significant enough to consider more serious underlying disease is often difficult.

In the United States, common viral and bacterial infections are overwhelmingly the most common cause of adenopathy. Infectious mononucleosis and cytomegalovirus (CMV) are important etiologies, but adenopathy is usually caused by common viral upper respiratory tract infections. Localized lymphadenitis is most often caused by staphylococci and beta-hemolytic streptococci.

Other infections, such as human immunodeficiency virus (HIV), malignancies, and autoimmune diseases, are less common causes of adenopathy.


Infections that are rarely observed in the United States, such as tuberculosis, typhoid fever, leishmaniasis, trypanosomiasis, schistosomiasis, filariasis, and fungal infections, are common causes of lymphadenopathy in developing nations.[3] HIV infections must be strongly considered in areas of high incidence.


In the United States, mortality and serious morbidity caused by adenopathy are unusual given the common infectious etiologies.


Race is not a factor in most lymphadenopathy. Rare causes may be associated with particular ethnic groups (eg, sarcoidosis in Africans, Kikuchi-Fujimori disease in Asians).


Sex does not influence childhood lymphadenopathy.


Adenopathy is most common in young children whose immune systems are responding to newly encountered infections. Adenopathy may be seen in one third of neonates and infants, usually in nodes that drain areas with mild skin irritation. Generalized adenopathy is rare in the neonate and suggests congenital infections, such as CMV. Adenopathy related to malignancy is rare at all ages. If diagnosed, it is often secondary to leukemia or neuroblastoma in younger children, and to Hodgkin lymphoma in adolescents.[5]


The differential diagnosis of acute lymphadenopathy is broad. A patient's medical history and review of systems is important in narrowing this differential. Upon examination, recognizing the pattern of lymph drainage aids in seeking an infectious focus.[6]

Although the underlying etiology is often self-limited infection, more serious underlying etiologies must be quickly recognized. Serious infections and malignancies are important considerations, as discussed in Outline - Etiologies of Lymphadenopathy.

In adolescents, screening for intravenous drug use and sexual activity is important.


Assess the size, location, and character of the adenopathy, along with any associated physical findings. Erythema, tenderness, warmth, and fluctuance suggests lymphadenitis, and nodes that are fixed (nonmoveable), matted together, firm, and nontender suggest malignancy, although this distinction is not invariable.


Generalized lymphadenopathy is defined as enlargement of more than 2 noncontiguous lymph node groups. A thorough history and physical examination are critical in establishing a diagnosis. Causes of generalized lymphadenopathy include infections, autoimmune diseases, malignancies, histiocytoses, storage diseases, benign hyperplasia, and drug reactions.

Regional lymphadenopathy involves enlargement of a single node or multiple contiguous nodal regions. Lymph nodes are clustered in groups throughout the body and are concentrated in the head and neck, axillae, mediastinum, abdomen, and along the vascular trunks of the extremities. Each group drains lymph from a particular region of the body. Knowledge of the pattern of lymph drainage aids in determining the etiology.

Outline - Etiologies of Lymphadenopathy

I. Generalized lymphadenopathy

  1. Infections
    1. Viral
      • Common upper respiratory infections
      • Infectious mononucleosis
      • CMV
      • Hepatitis A, B, and C
      • Acquired immunodeficiency syndrome
      • Rubella
      • Varicella
      • Measles
    2. Bacterial
      • Septicemia
      • Typhoid fever
      • Tuberculosis
      • Syphilis
      • Plague
    3. Protozoal - Toxoplasmosis
    4. Fungal - Coccidioidomycosis
  2. Autoimmune disorders and hypersensitivity states
    1. Juvenile rheumatoid arthritis
    2. Systemic lupus erythematosus
    3. Drug reactions (eg, phenytoin, allopurinol)
    4. Serum sickness
  3. Storage Diseases
    1. Gaucher disease
    2. Niemann-Pick disease
  4. Neoplastic and proliferative disorders
    1. Acute leukemias
    2. Lymphomas (Hodgkin, non-Hodgkin)
    3. Neuroblastoma
    4. Histiocytoses

II. Regional lymphadenopathy

  1. Cervical
    1. Viral upper respiratory infection
    2. Infectious mononucleosis
    3. Rubella
    4. Catscratch disease
    5. Streptococcal pharyngitis
    6. Acute bacterial lymphadenitis
    7. Toxoplasmosis
    8. Tuberculosis/atypical mycobacterial infection
    9. Acute leukemia
    10. Lymphoma
    11. Neuroblastoma
    12. Rhabdomyosarcoma
    13. Kawasaki disease
  2. Submaxillary and submental
    1. Oral and dental infections
    2. Acute lymphadenitis
  3. Occipital
    1. Pediculosis capitis
    2. Tinea capitis
    3. Secondary to local skin infection
    4. Rubella
    5. Roseola
  4. Preauricular
    1. Local skin infection
    2. Chronic ophthalmic infection
    3. Catscratch disease
  5. Mediastinal
    1. Acute lymphoblastic leukemia
    2. Lymphoma
    3. Sarcoidosis
    4. Cystic fibrosis
    5. Tuberculosis
    6. Histoplasmosis
    7. Coccidioidomycosis
  6. Supraclavicular
    1. Lymphoma
    2. Tuberculosis
    3. Histoplasmosis
    4. Coccidioidomycosis
  7. Axillary
    1. Local infection
    2. Catscratch disease
    3. Brucellosis
    4. Reactions to immunizations
    5. Lymphoma
    6. Juvenile rheumatoid arthritis
  8. Abdominal
    1. Acute mesenteric adenitis
    2. Lymphoma
  9. Inguinal
    1. Local infection
    2. Diaper dermatitis
    3. Insect bites
    4. Syphilis
    5. Lymphogranuloma venereum

Laboratory Studies

The laboratory evaluation of lymphadenopathy must be directed by the history and physical examination and is based on the size and other characteristics of the nodes and the overall clinical assessment of the patient. When a laboratory evaluation is indicated, it must be driven by the clinical evaluation.[13]

The following studies should be considered for chronic lymphadenopathy (>3 wk):

Evaluation of hepatic and renal function and a urine analysis are useful in identifying underlying systemic disorders that may be associated with lymphadenopathy. When evaluating specific regional adenopathy, lymph node aspirate for culture may be important if lymphadenitis is clinically suspected.

Titers for specific microorganisms may be indicated, particularly if generalized adenopathy is present. These may include Epstein-Barr virus, cytomegalovirus (CMV), Toxoplasma species, and human immunodeficiency virus (HIV).

Imaging Studies

Chest radiography may be helpful in elucidating mediastinal adenopathy and underlying diseases affecting the lungs, including tuberculosis, coccidioidomycosis, lymphomas, neuroblastoma, histiocytoses, and Gaucher disease.

Supraclavicular adenopathy, with its high associated rate of serious underlying disease, may be an indication for computed tomography (CT) scan of the chest, abdomen, or both.

A retrospective study by Razek et al indicated that diffusion-weighted magnetic resonance imaging (MRI) can be used to differentiate malignant from benign mediastinal lymphadenopathy in children. In the study, which included 29 children with mediastinal lymphadenopathy, patients were assessed with single-shot echo planar diffusion-weighted MRI, with the mean apparent diffusion coefficient (ADC) for the malignant condition being significantly below that for benign mediastinal lymphadenopathy.[14]  However, although this study may represent an important advance in the imaging of mediastinal/hilar lymphadenopathy, the results must be confirmed before the routine use of this technique can be recommended.

Positron-emission tomography (PET) scanning is not helpful as a screening tool as benign and malignant conditions may cause intense uptake.[15] However, PET scanning is helpful in the staging of lymphomas once a diagnosis is made.[16]

Ultrasonography may be helpful in documenting the extent of lymph node involvement and any changes in the lymph nodes.[17] In children with inguinal adenopathy or abdominal complaints, ultrasonography of the abdomen, CT scan of the abdomen, or both may be indicated.[18] Ultrasonography is rarely of diagnostic value for lymphadenopathy in childhood, even with advanced techniques.[19]

A study by Ying et al indicated that evaluation of the intranodal vascularity index is an effective means of diagnosing metastatic and tuberculous lymph nodes in patients with cervical lymphadenopathy. Using ultrasonographic images from 347 patients with palpable cervical lymph nodes, a customized computer program was used to quantify the intranodal vascularity index. With regard to distinguishing metastatic and tuberculous lymph nodes, the index was found to have a sensitivity and specificity of 80% and 73%, respectively; positive and negative predictive values of 91% and 51%, respectively; and an overall accuracy of 68%, when the cutoff vascularity index was 22%.[20]


The critical question is often whether or not to perform a lymph node biopsy; this requires an overall assessment of the history and physical examination as described above.

Images taken during and after a lymph node biopsy are shown below.

View Image

A lymph node biopsy is performed. Note that a marking pen has been used to outline the node before removal and that a silk suture has been used to pro....

View Image

A lymph node after removal by means of biopsy, which was performed completely under a local anesthetic technique.

View Image

A gross image of a node following excision. The cut surface of the node shows the typical fish-flesh appearance seen with lymphoma.

Treatment with antibiotics covering bacterial pathogens frequently implicated in lymphadenitis, followed by reevaluation in 2-4 weeks is reasonable, if clinical findings suggest lymphadenitis. Benign reactive adenopathy may be safely observed for months.[6]

If the size, location, or character of the lymphadenopathy suggests malignancy, the need for laboratory studies and biopsy is more urgent. If laboratory testing is inconclusive, a lymph node biopsy is immediately indicated.

Fine needle aspiration and core needle biopsy yield small samples with limited ability to perform flow cytometry and chromosomal analysis; most pediatric hematologists and pathologists prefer excisional biopsy.

Excisional biopsy also has limitations and may yield a definitive diagnosis in only 40-60% of patients because of inadequate specimen size, improper handling, or node-sampling error (eg, Hodgkin lymphoma) may be associated with reactive changes in surrounding nodes; sampling more accessible nodes may miss the underlying malignancy.

The surgeon should therefore biopsy larger, firmer, and most recently enlarging nodes, even if it is technically difficult, with appropriate handling of the specimen. If an excisional biopsy does not reveal the diagnosis, a second biopsy may be indicated.

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a widespread technique for tissue sampling from hilar and mediastinal lymph nodes; however, the predominant finding in routine care is a nondiagnostic cytology in more than 70% of patients.[21]

A multicenter study by Dhooria et al indicated that, as in adults, EBUS-TBNA and endoscopic ultrasonography with an echobronchoscope-guided fine-needle aspiration (EUS-B-FNA) can be safely and effectively used in children with mediastinal lymphadenopathy, providing a good diagnostic yield.[22]

Histologic Findings

Histiologic findings depend on the underlying etiology of the lymphadenopathy. Nonspecific changes consistent with reactive adenopathy are often the only findings. This is helpful in ruling out malignancy, histiocytoses, granulomatous disorders, and storage diseases. Specific infections can be diagnosed if tissues are appropriately stained.

When examining the tissue, histiologic findings are often inadequate. Flow cytometric and chromosomal analysis may provide critical information to permit a diagnosis to be established.


Staging is relevant only when a specific malignancy is diagnosed as the etiology of lymphadenopathy.

Medical Care

Treatment is determined by the specific underlying etiology of lymphadenopathy.

Surgical Care

Surgical care usually involves a biopsy. If lymphadenitis is present, aspirate may be needed for culture, and removal of the affected node may be indicated.


Consultation with a pediatric hematologist, pediatric oncologist, or both is often useful, especially if the adenopathy seems to be more than reactive. Often, the most important decision for these children is whether further evaluation is necessary at all; experience in evaluating these children is frequently very helpful. The ability to provide a careful assessment of the peripheral blood smear may be particularly important.

Surgical consultation is usually helpful for lymph node biopsy, needle aspiration for culture, and for incision and drainage of obviously infected fluctuant nodes.


Diet plays little role in the pathophysiology of lymphadenopathy.

Internationally, many of the infectious etiologies may be associated with a higher risk of malnutrition.


Limitations on activity usually involve associated acute-onset splenomegaly. Any patient with an acutely enlarged spleen may need to be restricted from contact sports.

In infectious mononucleosis, rupture of the spleen can occur with relatively little trauma and can be fatal.

Medication Summary

No specific medical therapy for lymphadenopathy is acknowledged.

Therapy is directed at the specific diagnosis, once established, and when appropriate.

Further Outpatient Care

Further outpatient treatment depends on establishing a diagnosis and determining management of that diagnosis.

Further Inpatient Care

Additional inpatient treatment depends on establishing the diagnosis and determining management based on that diagnosis.

Inpatient & Outpatient Medications

Inpatient and ambulatory medications depend on the specific underlying etiology of the lymphadenopathy.


Transfer of the patient usually depends on the specific diagnosis. Patients who develop superior vena cava syndrome with either respiratory symptoms or obstruction to blood flow require emergency medical care and may require transfer to a tertiary care center.


Complications are usually related to the specific underlying disorder causing the lymphadenopathy; however, the lymphadenopathy itself can cause potentially serious complications.


The prognosis of lymphadenopathy almost entirely depends on the underlying etiology. Patients with specific complications, such as superior vena cava syndrome, are at risk unless this specific complication is managed. Their prognosis is dependent on the management of the neoplastic process resulting in superior vena cava syndrome.

Patient Education

Patient and family education depends on the specific etiology of the lymphadenopathy.


Vikramjit S Kanwar, MBBS, MBA, MRCP(UK), FAAP, Professor of Pediatrics, Albany Medical College; Chief, Division of Pediatric Hematology-Oncology, John and Anna Landis Endowed Chair for Pediatric Hematology-Oncology, Medical Director, Melodies Center for Childhood Cancer and Blood Disorders, Albany Medical Center

Disclosure: Nothing to disclose.


Richard H Sills, MD, Professor of Pediatrics, Upstate Medical University

Disclosure: Nothing to disclose.

Specialty Editors

Mary L Windle, PharmD, Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Larry I Lutwick, MD, Professor of Medicine, State University of New York Downstate Medical School; Director, Infectious Diseases, Veterans Affairs New York Harbor Health Care System, Brooklyn Campus

Disclosure: Nothing to disclose.

Chief Editor

Russell W Steele, MD, Clinical Professor, Tulane University School of Medicine; Staff Physician, Ochsner Clinic Foundation

Disclosure: Nothing to disclose.

Additional Contributors

Gary J Noel, MD, Professor, Department of Pediatrics, Weill Cornell Medical College; Attending Pediatrician, New York-Presbyterian Hospital

Disclosure: Nothing to disclose.


The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous author Stephanie Jorgensen, MD, to the original writing and development of this article.


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  21. Lange TJ, Kunzendorf F, Pfeifer M, Arzt M, Schulz C. Endobronchial ultrasound-guided transbronchial needle aspiration in routine care - plenty of benign results and follow-up tests. Int J Clin Pract. 2012 May. 66(5):438-45. [View Abstract]
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A lymph node biopsy is performed. Note that a marking pen has been used to outline the node before removal and that a silk suture has been used to provide traction to assist the removal.

A lymph node after removal by means of biopsy, which was performed completely under a local anesthetic technique.

A gross image of a node following excision. The cut surface of the node shows the typical fish-flesh appearance seen with lymphoma.

A lymph node biopsy is performed. Note that a marking pen has been used to outline the node before removal and that a silk suture has been used to provide traction to assist the removal.

A lymph node after removal by means of biopsy, which was performed completely under a local anesthetic technique.

A gross image of a node following excision. The cut surface of the node shows the typical fish-flesh appearance seen with lymphoma.