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Granulomatous Hepatitis
Acknowledgements
Substantial material for this chapter is taken from the chapter of the same name and topic by Dr. Beverly Connelly in the previous edition.
Histologically, evident granulomas in the liver are referred to as granulomatous hepatitis . Granulomas are reported in 2%–15% of liver biopsy specimens from adults and 4%–7% of specimens from children. , Granulomas are most often a manifestation of an underlying systemic process, although can be an incidental finding, as in biopsies performed in prospective organ donors, or can be a manifestation of a disorder primarily of the liver. Depending on the underlying cause, serum hepatic enzyme levels may be normal, minimally, or severely abnormal. ,
Pathogenesis And Pathologic Findings
The hallmark of hepatic granulomas is epithelioid cells, which are activated macrophages transformed to resemble epithelial cells. Granuloma formation is initiated when monocytes and macrophages migrate into an area of inflammation in response to triggering by intracellular microbial antigens, foreign body reactions, and host immunologic hypersensitivity responses. A Th1 or Th2 pathway can be active in granuloma formation. The Th1 immune response classically is involved in tuberculosis and sarcoidosis, and the Th2 response occurs with parasitic infections. T-lymphocyte–derived tumor necrosis factor (TNF) plays a key role in granuloma formation, a finding supported by the enhanced risk to pathogens inducing granulomatous infections in patients receiving TNF-inhibitor agents. ,
Hepatic granulomas are 50–300 mm in diameter, and their morphology varies from clusters of epithelioid cells to well-developed granulomas rimmed by lymphocytes. , Epithelioid cells can merge to form multinucleated giant cells. Central caseation or abscess formation can occur. Distribution of epithelioid cells often is patchy, and the small granulomas may be identified only with serial tissue section analysis. ,
Histologic features can suggest specific diagnoses. Central caseation with epithelioid cells in a radial array at the periphery is typical of tuberculosis. Granulomas are large and loose in sarcoidosis, without pattern or caseation, although there can be central eosinophilic necrosis and multinucleated giant cells. , In chronic granulomatous disease of childhood, pigmented macrophages are found in architecturally normal liver, and necrotizing granulomas are found in areas of active inflammation. , Bartonella henselae causes granulomas with stellate microabscess. , Eosinophilic infiltrates help distinguish hepatic granulomas caused by parasitic infestations, and a portion of the larva may be seen within the granulomas of visceral larva migrans or the ova in schistosomiasis. , Eosinophilic granules also can be seen with histoplasmosis.
Special histologic stains and techniques should be used when an infectious cause is suspected. Acid-fast bacilli (AFB) are demonstrated infrequently in granulomas caused by Mycobacterium tuberculosis , whereas large numbers of AFB usually are found in immunocompromised patients infected with nontuberculous mycobacteria. Immunohistochemistry and nucleic acid amplification techniques, including in situ amplification, can be useful for identifying various pathogens in tissues. ,
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