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A 19-year-old man comes to your clinic complaining of fever, headache, sore throat, and fatigue that started about 2 weeks ago. He has also noticed multiple swollen lymph glands in the front of his neck. He denies any rhinorrhea or cough. He is concerned because the lymph glands are sore to touch, and his symptoms are not improving.

  • What additional questions are required to learn more about his swollen lymph glands?
  • How would you classify his lymphadenopathy?
  • What are the possible causes of enlarged lymph nodes?
  • How does the interviewer establish a presumptive diagnosis using open-ended questions followed by more focused history taking?
  • How do you distinguish benign causes of lymphadenopathy from more serious ones that require further evaluation?

Lymphadenopathy is the enlargement of 1 or more lymph nodes. Patients may be alerted to the presence of enlarged lymph nodes by noticing visible nodular swelling, palpability, pain, or tenderness in 1 or more lymph node regions. It is normal to be able to palpate small lymph nodes in the neck and groin regions but generally not in the supraclavicular fossa, axilla, epitrochlear, or popliteal regions.

Lymphadenopathy generally results from infiltration of lymph nodes by inflammatory or neoplastic cells, proliferation of resident lymphocytes, or expansion due to hemorrhage or abscess formation. In primary care settings, lymphadenopathy is rarely due to malignancy; upper respiratory tract infections or nonspecific conditions account for over two-thirds of cases. However, the risk of malignancy increases with age and other factors.

Careful history taking is important in determining the cause of lymphadenopathy. Patients may be concerned or even anxious that lymphadenopathy may be a manifestation of cancer. The medical interview can assist in excluding malignancy or other serious underlying disease in most patients and inform subsequent evaluation for the remainder.

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Lymphadenopathy1Abnormal enlargement of 1 or more lymph nodes (> 1.0 cm in adults; > 1.5 cm in children and adolescents).
Generalized lymphadenopathy2Lymph node enlargement affecting multiple body regions.
Localized lymphadenopathy2Lymph node enlargement limited to a single body region (eg, cervical, inguinal).

In primary care practice, more than two-thirds of patients with lymphadenopathy have nonspecific causes or upper respiratory illnesses (viral or bacterial), and less than 1% have a malignancy.1–4 In one study, 84% of patients referred for evaluation of lymphadenopathy had a “benign” diagnosis. The remaining 16% had a malignancy (lymphoma or metastatic adenocarcinoma). Of the patients with benign lymphadenopathy, 63% had a nonspecific or reactive etiology (no causative agent found), and the remainder had a specific cause demonstrated, most commonly infectious mononucleosis, toxoplasmosis, or tuberculosis. Thus, the vast majority of patients with lymphadenopathy will have a nonspecific etiology requiring few if any diagnostic tests.3

A comprehensive discussion of the myriad agents and diseases associated with lymphadenopathy is beyond the scope of this chapter but can be found elsewhere....

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