Practice Essentials
Lymphadenopathy, an enlargement of the lymph nodes, 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 a viral infection. 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).
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 a lymph node's 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.
Pathophysiology
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).
Epidemiology
Frequency
United States
The precise incidence of lymphadenopathy is not known, but estimates of palpable adenopathy in childhood vary from 38-45%, [3] and lymphadenopathy is one of the most common clinical problems encountered in pediatrics. [4] 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.
International
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. [5] HIV infections must be strongly considered in areas of high incidence.
Mortality/Morbidity
In the United States, mortality and serious morbidity caused by adenopathy are unusual given the common infectious etiologies.
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Malignancies, such as leukemia, lymphomas, and neuroblastoma, are the primary causes of mortality in the United States. [6]
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Significant morbidity and mortality are also associated with autoimmune disorders (eg, juvenile rheumatoid arthritis, systemic lupus erythematosus), histiocytoses, and storage diseases.
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HIV is an uncommon cause of adenopathy in the United States, but its associated mortality requires consideration.
Race
Race is not a factor in most lymphadenopathy. Rare causes may be associated with particular ethnic groups (eg, sarcoidosis in Africans, Kikuchi-Fujimoto disease in Asians).
Sex
Sex does not influence childhood lymphadenopathy.
Age
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. [7]
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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.
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A lymph node after removal by means of biopsy, which was performed completely under a local anesthetic technique.
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A gross image of a node following excision. The cut surface of the node shows the typical fish-flesh appearance seen with lymphoma.
