What is the role of biopsies and tissue sampling in the workup of fever of unknown origin (FUO)?

Updated: May 17, 2021
  • Author: Sandra G Gompf, MD, FACP, FIDSA; Chief Editor: Michael Stuart Bronze, MD  more...
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Obtain cultures for bacteria, mycobacteria, and fungi in all normally sterile tissues and liquids that are biopsied. This may include cerebrospinal fluid (CSF), pleural or peritoneal fluid, and fluid from the liver, bone marrow, and lymph nodes.

Biopsies are easily performed in enlarged accessible lymph nodes, other peripheral tissues, and bone marrow. Superficial enlarged lymph nodes of highest yield on biopsy include posterior cervical, supraclavicular or infraclavicular, and epitrochlear nodes. Deep nodes of highest yield are the hilar, mediastinal, or retroperitoneal lymph nodes. [25]

Bone marrow biopsy is of highest yield with unexplained abnormality of the CBC count (hematologic malignancy) and granulomatous disease such as sarcoidosis, tuberculosis, or histoplasmosis. [25]

Liver biopsy rarely yields helpful data in patients without abnormal liver function test results or abnormal liver findings (observed on CT scan or ultrasonography). Liver biopsy may be necessary to characterize granulomatous or autoimmune hepatitis.

The decision to biopsy is more difficult if it entails an exploratory surgical procedure (eg, laparotomy). [26] This is rarely indicated (eg, when imaging techniques are nondiagnostic and an intra-abdominal source is suspected), particularly considering the generally benign course of FUO that remains undiagnosed after extensive workup.

Arterial biopsy is rarely associated with hematoma, ischemic complications, or nerve damage, given that nerves and vessels often follow a similar course. This may be warranted, however, for the diagnosis of polyarteritis nodosa and giant cell arteritis, as these conditions may be disabling or life-threatening if left untreated; these are among the few conditions associated with an erythrocyte sedimentation rate of 100 mm/hour or greater. Biopsy of small- or medium-sized arteries demonstrate white blood cell infiltrate in polyarteritis nodosa. Temporal artery biopsy is necessary for definitive diagnosis of giant cell arteritis, provided a sufficient length of artery is excised. 

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