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This chapter is intended to serve as a guide to the evaluation of patients who present with enlargement of the lymph nodes (lymphadenopathy) or the spleen (splenomegaly). Lymphadenopathy is a rather common clinical finding in primary care settings, whereas palpable splenomegaly is less so.




Lymphadenopathy may be an incidental finding in patients being examined for various reasons, or it may be a presenting sign or symptom of the patient’s illness. The physician must eventually decide whether the lymphadenopathy is a normal finding or one that requires further study, up to and including biopsy. Soft, flat, submandibular nodes (<1 cm) are often palpable in healthy children and young adults; healthy adults may have palpable inguinal nodes of up to 2 cm, which are considered normal. Further evaluation of these normal nodes is not warranted. In contrast, if the physician believes the node(s) to be abnormal, then pursuit of a more precise diagnosis is needed.





Lymphadenopathy may be a primary or secondary manifestation of numerous disorders, as shown in Table 4-1. Many of these disorders are infrequent causes of lymphadenopathy. In primary care practice, more than two-thirds of patients with lymphadenopathy have nonspecific causes or upper respiratory illnesses (viral or bacterial), and <1% have a malignancy. 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 diagnostic tests.


The physician will be aided in the pursuit of an explanation for the lymphadenopathy by a careful medical history, physical examination, selected laboratory tests, and perhaps an excisional lymph node biopsy.

The medical history should reveal the setting in which lymphadenopathy is occurring. Symptoms such as sore throat, cough, fever, night sweats, fatigue, weight loss, or pain in the nodes should be sought. The patient’s age, sex, occupation, exposure to pets, sexual behavior, and use of drugs such as diphenylhydantoin are other important historic points. For example, children and young adults usually have benign (i.e., nonmalignant) disorders that account for the observed lymphadenopathy such as viral or bacterial upper respiratory infections; infectious mononucleosis; toxoplasmosis; and, in some countries, tuberculosis. In contrast, after age 50, the incidence of malignant disorders increases and that of benign disorders decreases.

The physical examination can provide useful clues such as the extent of lymphadenopathy (localized or generalized), size of nodes, texture, presence or absence of nodal tenderness, signs of inflammation over the node, skin lesions, and splenomegaly. A thorough ear, nose, and throat (ENT) examination is indicated in adult patients with cervical adenopathy and a history of tobacco use. Localized or regional adenopathy implies involvement of a single anatomic area. Generalized adenopathy has been defined as involvement of three or more noncontiguous lymph node areas. Many of the causes of lymphadenopathy (Table 4-1) can produce localized or generalized adenopathy, so this distinction is of limited utility in the differential diagnosis. Nevertheless, generalized lymphadenopathy is frequently associated with nonmalignant disorders such as infectious mononucleosis (Epstein-Barr virus [EBV] or cytomegalovirus [CMV]), toxoplasmosis, AIDS, other viral infections, systemic lupus erythematosus (SLE), and mixed connective tissue disease. Acute and chronic lymphocytic leukemias and malignant lymphomas also produce generalized adenopathy in adults.

The site of localized or regional adenopathy may provide a useful clue about the cause. Occipital adenopathy often reflects an infection of the scalp, ...

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