Hepatocellular Carcinoma in Tyrosinemia Related Cirrhosis.
Katharine Van Patten, Kisha Mitchell. Yale University, New Haven
Background: Hereditary tyrosinemia type I is a rare autosomal recessive disorder resulting in the accumulation of toxic tyrosine metabolites in the liver and kidneys with progressive organ damage. Tyrosinemia has a documented rate of neoplastic transformation that is significantly greater than that of other liver diseases with cirrhosis, both in the adult and pediatric population. Classification of liver nodules is difficult from both a radiologic and pathologic perspective. The goal of our study was to evaluate the imunohistochemical profile of nodules in the setting of tyrosinemia-related cirrhosis for features of dysplastic nodules and hepatocellular carcinoma (HCC).
Design: Three patients who underwent orthotopic liver transplant in 2010 for tyrosinemia were identified from the pathology database. The demographic data, gross photographs and microscopic slides were reviewed. Reticulin, CD34, polyclonal CEA, AFP, heat-shock protein-70 (HSP-70, Abcam) and glypican-3 (Cell Marque) were performed on dominant nodules. Two pathologists reviewed the morphology of each case and scored each stain. Greater than 10% staining was considered positive.
Results: All livers had mixed micronodular/macronodular cirrhosis, with one predominantly macronodular. Case 1 was a 1 year old boy who had a 2.8 cm dominant nodule with marked steatosis, focal pseudoacinar formation and small and large cell changes. This nodule was AFP and HSP-70 positive with rare positivity observed in nodules without obvious atypia. Case 2 was a 2 year old boy who had three dominant nodules, up to 1.9. Within these nodules, there were areas of small cell change, nuclear atypia and pleomorphism and steatosis as well as subcentimeter nodules with similar changes. HSP-70 was positive only in atypical nodules. Case 3 was a 5 month old boy with three dominant nodules, up to 1.4 cm in diameter with moderate pleomorphism. AFP was positive in these atypical nodules. All 3 cases showed intact reticulin network with patchy peripheral CD34 staining, while GPC3 was positive in atypical nodules in all three. GPC3 was also positive in numerous nodules in cases 2 and 3.
Conclusions: Nodules in tyrosinemia show a spectrum of changes ranging from bland cirrhosis to well defined HCC. We have demonstrated that AFP, GPC3 and HSP are helpful in identifying foci of HCC within the liver and in dysplastic nodules, while CD34 and reticulin are not. The staining of these reported markers of neoplasia in nodules without significant atypia supports that the rate of neoplastic progression may be accelerated in tyrosinemia even in early stages of cirrhosis.
Category: Liver & Pancreas
Tuesday, March 1, 2011 9:30 AM
Poster Session III # 262, Tuesday Morning