FNH-Like Lesions and Glutamine Synthetase Expression in the Liver in Hereditary Hemorrhagic Telangiectasia.
Soo-Jin Cho, Ian Wanless, Valerie Paradis, Rish Pai, Paulette Bioulac-Sage, Venancio Alves, Tulio Souza, Hala Makhlouf, Peter Schirmacher, Kimberley Evason, Linda Ferrell. Univ Calif, San Francisco; Queen Elizabeth II Health Sciences Center, Halifax, Canada; Hospital Beaujon, Clichy, France; Washington Univ, St. Louis; Hospital Pellegrin, Bordeaux, France; Univ Sao Paulo, Brazil; Hospital Alianca, Salvador, Brazil; AFIP, Washington, DC; Univ Hospital, Heidelberg, Germany
Background: Hereditary hemorrhagic telangiectasia (HHT) is a familial disease with arterial enlargement and large shunts in many organs, including the liver. In addition to telangiectases, arterialized nodules are often seen on hepatic imaging, some of which have been called focal nodular hyperplasia (FNH). In livers without HHT, FNH shows artery-portal vein shunts and a distinctive pattern of glutamine synthetase (GS) expression. In this study, we describe liver histology from 16 patients with HHT, concentrating on the vascular lesions (telangiectases), FNH-like lesions, and GS expression.
Design: Specimens (16) ranged from wedge biopsies (1/16) to partial (1/16) and total hepatectomies (14/16; including 1 autopsy). H&E, CD34 and GS stains were evaluated.
Results: Telangiectases typical of HHT were present in all cases. Surrounding sinusoids showed dilation and arterialization, as evidenced by increased CD34 staining (10/12). The extent of telangiectases varied from minimal (1/16) to almost confluent (1/16). 5 cases showed FNH-like lesions, defined by a cluster of component nodules forming a ring of hyperplastic hepatocytes surrounding a central fibrous region. Component nodules consisted of hepatocytes in 1-2-cell-wide plates, supplied by a portal tract containing an artery, often with ductular elements at the portal-parenchymal interface. The central fibrous region contained larger arteries, often with ductules but no ducts or portal veins. An obstructed hepatic or portal vein could be seen in the vicinity of each nodule. GS showed decreased staining around telangiectases, but showed characteristic “map-like” staining in the lesions. Obstructed veins were also seen in cases without lesions (5/11); 1 of these cases showed a background of cirrhosis and 2 cases showed ischemic necrosis.
Conclusions: Telangiectases in HHT provide local high flow and pressure, and remodel into a non-communicating shunt over a long period of development. We propose that if this flow pattern is acutely disturbed, by congestive injury or thrombus in a portal or hepatic vein, the flow must be accommodated by collaterals to normal adjacent hepatic vein drainage beds. The new flow causes hepatocyte hyperplasia, with increased GS expression, leading to the formation of FNH-like lesions.
Category: Liver & Pancreas
Tuesday, March 1, 2011 1:30 PM
Platform Session: Section C, Tuesday Afternoon