S. Ambrosi, M.D., P. Di Zitti, M, M., A. Baiocchini, M. D.
The current case showed the histopathologic features of AGCH. Several pathogenetic mechanisms possibly underlying GCT have been proposed. Viral infection seems to be an important triggering factor, hepatitis viruses type B and C, or even A, being most frequently implicated. HIV infection itself can account for GCT , either directly or through a Cytomegalovirus hepatitis ( 3 ).
Recently Phillis et al. found GCT in paramyxovirus infections and recalled that they are frequently associated with GCT of every involved tissue. In fact, this is a regular pathologic change in measles pneumonitis and Warthin-Finkeldy cells are often found in damaged lymphatic tissue ( 9 ). Drug toxicity is another common cause of GCT. Metothrexate is the most frequently implicated drug, but other agents such as 6-mercaptopurine, clometacin, chlorpromazine, vinyl chloride and p-aminosalicilic acid are similarly involved in the pathogenesis of this peculiar cellular change ( 1 ). Finally, AGCH has been described in autoimmune hepatitis or autoimmune disorders such hemolitic anemia ( 5, 8 ). Pappo et al reported the occurrence of GCH following orthotropic liver transplantation thus suggesting a possibly combined immunopathologic and infectious pathogenesis ( 1 ).
It is unclear how giant cells develop. As a matter of fact their immunohistochemical cytokeratin profile recapitulates that of normal hepatocyte since they are immunopositive for CK 8 and 18, but negative for CK 7 and 19 ( 11 ). We, in addition, documented a significant granular immunopositivity for CD 68, a specific lysosomal product ( 2 ), thus demonstrating their fagocitic activity. They may represent a true syncitium due to merging of degenerating hepatocytes into a multinucleated cell, or may represent a peculiar pattern of cellular regeneration following liver cell necrosis ( 2 ). The absence of mitotic figures and the presence of degenerative organelles is suggestive of cellular fusion, but since not always cell membrane or other cytoplasmic organelles have been found by electron microscopy, it´s not possible to keep out definitely a regenerative process. As a matter of fact, during the neonatal period, GCT is a common response to many liver injuries such as hepatocellular cholestatic disease following neonatal hepatitis or as a consequence of bile duct disorders such as biliary atresia and bile duct paucity, but it may be present also in neonatal hemocromatosis, viral hepatitis as in the adult, and * -1-antitrypsin deficiency.
GCH can thus be considered as a morphologic reaction pattern. As its been shown, there are a lot of possible etiologic causes, the first suddivision being between neonatal setting and adult life.
In our case there is neither evidence of viral hepatitis, nor of other infectious diseases recently associated with AGCH, expecially paramyxoviruses diseases; HIV is negative and the patient had no history of liver damage due to alcohol or drugs assumption. There are no signs or symptoms of previous hepatic derangement such as cholangitis or primary biliary chirrosis . Autoimmune disorders seem to be excluded, due to some autoantibodies negativity, but other laboratory investigations, i.e. rare or more specific autoantibodies, are needed to rule out an immunologic etiology.
At the moment the diagnosis is a descriptive one. Further laboratory information must be correlated to establish, if possible, an etiologic diagnosis and at present time our case must be regarded as an idiopathic AGCH ( 10 ).