A 2-year-old girl presented to her pediatrician with a one month history of swollen glands in her neck and under her arms. Physical examination revealed non-tender firm lymphadenopathy in the anterior and posterior lymph node chains bilaterally (Figure 33-1). Work-up revealed anemia, neutropenia and thrombocytopenia. Biopsy of the lymph nodes and bone marrow biopsy showed acute lymphoblastic leukemia. She underwent induction chemotherapy and has responded well.

Lymphadenopathy refers to nodes that are abnormal in either size, consistency, or number. In children, causes of lymphadenopathy can be divided into two large groups-inflammatory versus malignant. Cervical adenopathy due to inflammatory causes is by far the most common. Malignancy is less common but must be considered in the differential diagnosis based on certain concerning features in the history and physical exam.

Lymphadenitis, lymph node enlargement.

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  Almost all children develop lymphadenopathy at some point during childhood with nearly 2/3 of them developing enlarged nodes within infancy.²

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  Lymph nodes are organized centers of immune cells that filter antigenic material such as infectious agents from lymphatics draining from areas of inflammation.

  
  
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  When activated due to infection or antigenic stimulation, the nodes enlarge in size largely due to proliferation of cells intrinsic to the node such as plasma cells, macrophages, and others.

  
  
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  Enlargement of nodes can also occur due to infiltration of malignant cells.²

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  Risk factors for inflammatory causes of lymphadenopathy are most commonly associated with exposure to pathogens.

  
  
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  Viral illnesses that lead to lymphadenopathy are common in childcare centers.

  
  
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  Parasitic and atypical infections can occur from a variety of exposures, including Bartonella henselae infection from a cat scratch and toxoplasmosis from exposure to cat feces.

  
  
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  Lymphadenopathy associated with human immunodeficiency virus (HIV) infection can result from perinatal exposure, exposure to intravenous drug use, or unprotected sexual behavior.

  
  
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  Certain infectious etiologies of lymphadenopathy can be regional in nature, such as exposure to coccidiomycosis in the southwest US and histoplasmosis exposure in the southeastern or central US.

  
  
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  Medications, such as phenytoin or penicillin, can be associated with the development of lymphadenopathy.

  
  
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  Odontogenic infections may cause a lymphadenopathy adjacent to the site of the infection.

  
  
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  Risk factors for malignant causes of lymphadenopathy include exposures to Epstein-Barr virus (EBV) in cases of lymphoma or nasopharyngeal carcinoma.

Clinical Features

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  Localized lymphadenopathy occurs in 75 percent of the cases and generalized lymphadenopathy in the rest of the cases.

  
  
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  Of all the locations that localized lymphadenopathy can occur, head and neck manifestation occurs in 55 percent of the cases.¹

  
  
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  Acute unilateral adenopathy is most likely due to streptococcal, staphylococcal, or viral infections (Figures 33-2 and 33-3).

  
  
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  Acute bilateral adenopathy tends to be due to systemic infections, such as infectious mononucleosis or viral upper respiratory infections (Figure 33-4).

  
  
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  Subacute or chronic lymphadenopathy usually occurs due to slow-growing bacterial or viral infections such as cat-scratch disease or nontuberculous mycobacterial infection (Figures 33-5 and 33-6).

  
  
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  Inflammatory masses are generally tender and mobile. Exceptions include some of the causes of subacute or chronic lymphadenopathy, such as nontuberculous mycobacterial infection, which is usually a nontender lymphadenopathy with fixation of the node to the skin (see Figure 33-5 and 33-6).

  
  
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  Features that may raise concern for the possible presence of malignancy include persistent nontender adenopathy with a size greater than 2 cm, constitutional symptoms such as fevers, night sweats, or weight loss, and adenopathy in certain unusual locations such as the supraclavicular region and in some cases, the posterior neck.³

  
  
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  In addition, firm, rapidly enlarging, fixed nodes should alert concern for malignancy (Figure 33-7).