Granulomas can be present in the liver in a variety of conditions. Their detection in the liver may be the first clue to an ongoing systemic disease. Although the granulomas themselves rarely cause structural liver damage, it is important to identify the underlying systemic disease since it might have prognostic and therapeutic implications. Careful consideration of associated clinical symptoms and characterization of the appearance and localization of the granulomas within the liver usually leads to a definitive diagnosis.
A granuloma is a circumscribed lesion that forms as a result of an inflammatory reaction in body tissues. It is characterized by a central accumulation of mononuclear cells, primarily macrophages, with a surrounding rim consisting of lymphocytes and fibroblasts. The lesions are distinct from nearby uninvolved tissue (picture 1).
Early in the development of the granuloma, lesions may appear as punched-out clusters of histiocytes or lymphocytes. The granulomas evolve with stimulation of mononuclear cells from a variety of cytokines. Activated macrophages are transformed to resemble epithelial cells (referred to as epithelioid cells), which characteristically have abundant, pale cytoplasm. Adjacent macrophages may fuse, forming multinucleated giant cells. Granulomas infiltrated by eosinophils are suggestive of a drug reaction or parasitic infection.
The cells within the granuloma are capable of secreting a variety of proteins. As an example, epithelioid cells from patients with sarcoidosis secrete lysozyme, collagenase, and angiotensin converting enzyme (ACE). Elevated serum levels of ACE are characteristic of active sarcoidosis . (See "Clinical manifestations and diagnosis of pulmonary sarcoidosis".)
The histologic features of the granulomas and their location may be helpful for narrowing the differential diagnosis. Four histologic variants of hepatic granulomas have been recognized, the first two of which are most common in the United States :