A 43-year-old woman complains of fatigue and night sweats associated with itching for 2 months. On physical examination, there is diffuse nontender lymphadenopathy, including small supraclavicular, epitrochlear, and scalene nodes. CBC and chemistry studies (including liver enzymes) are normal. Chest x-ray shows hilar lymphadenopathy. Which of the following is the best next step in evaluation?

The long-term nature of these symptoms, the fact that the nodes are nontender, and their location (including scalene and supraclavicular) all suggest the likelihood of malignancy. Although infectious mononucleosis and toxoplasmosis can cause diffuse lymphadenopathy, these infections are usually associated with other evidence of infection such as pharyngitis, fever, and atypical lymphocytosis in the peripheral blood. It would be unusual for the lymphadenopathy associated with these infections to persist for 2 months. Serum angiotensin-converting enzyme level is a nonspecific test for sarcoidosis but is also elevated in other granulomatous diseases and is not sensitive or specific enough to be used as an initial diagnostic test. Lymphadenopathy associated with sarcoidosis requires a biopsy for diagnosis. In this patient, an excisional biopsy is necessary primarily to rule out malignancy, particularly lymphoma. Needle aspiration biopsy, useful for the diagnosis of metastatic carcinoma, is insufficient to diagnose suspected lymphoma, where assessment of the lymph node architecture is important.