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Liver Involvement in the Histiocytic Disorders of Childhood

  • Perspectives in Pediatric Pathology
  • Published:
Pediatric and Developmental Pathology

Abstract

The liver can be involved directly, by infiltration, and indirectly—by remote effects—in the histiocytoses of childhood. Langerhans cell disease, the most well recognized of these, infiltrates the liver directly but has a remarkable selectivity for the bile ducts. Early involvement is by Langerhans cell histiocytosis (LCH) infiltration leading to a sclerosing cholangitis and, eventually, biliary cirrhosis. Gamma glutamyl transpeptidase is a sensitive indicator of liver infiltration in a child with LCH. The indirect effects on the liver of LCH elsewhere in the body are mediated through an accompanying macrophage activation syndrome that is most likely responsible for hepatomegaly and hypoalbuminemia but without direct infiltration. These indirect effects are completely reversible. Juvenile xanthogranuloma/xanthoma disseminatum, a related dendritic cell disorder that can have systemic manifestations, has a strikingly different pattern, with a predominantly portal infiltrate spilling over into the adjacent lobule but sparing the biliary tree. The biology of the liver lesions is not clear but regression has been documented. Myeloproliferative disorders and myeloid leukemias can express CD1a and/or S100 protein, mimicking LCH but distinguished by their sinusoidal pattern. The primary macrophage histiocytoses such as the familial hemophagocytic syndromes can lead to severe liver damage. Although a portal lymphohistiocytic infiltrate is most characteristic, it is probably cytokine-mediated hepatocellular damage that can cause substantial functional impairment or even hepatic failure as a presenting feature. Liver involvement in other, more unusual histiocytic disorders, is also illustrated.

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ACKNOWLEDGMENTS

Support for the review and study of the histiocytic disorders has been generously provided through the Marjory K. Harmer Pediatric Pathology Endowment, Children’s Hospital of Pittsburgh. I owe a debt of gratitude to Blaise Favara, MD, who shared his cases with me and whose paper on this same topic is the gold standard. My thanks also to those who generously share their cases.

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  1. Department of Pathology, Children’s Hospital of Pittsburgh, University of Pittsburgh School of Medicine, 3705 Fifth Avenue, Pittsburgh, PA, 15213, USA

    Ronald Jaffe

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Jaffe, R. Liver Involvement in the Histiocytic Disorders of Childhood. Pediatr. Dev. Pathol. 7, 214–225 (2004). https://doi.org/10.1007/s10024-003-9876-z

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