Fibrolamellar Carcinomas Are Positive for CD68
HM Ross, MM Yeh, TT Wu, HR Makhlouf, HH Daniel, P Vivekanandan, R Kannangai, M Torbenson. Johns Hopkins Hospital, Baltimore; University of Washington, Seattle; Mayo Clinic, Rochester; Armed Forces Institute of Pathology, Washington, DC
Background: Fibrolamellar carcinomas are a unique type of liver carcinoma that arise in non-cirrhotic livers of young individuals. Despite their distinctive appearance, recent studies have demonstrated a lack of consistency in how fibrolamellar carcinomas are diagnosed by pathologists. Interestingly, gene expression studies show an increased expression of CD68 in these tumors. The CD68 gene encodes for a transmembrane glycoprotein located within lysozymes and endosomes. Thus, macrophages as well as other cell types rich in lysozomes/endosomes are CD68 positive. In this study, the staining pattern of CD68 was explored in the epithelial cells of both fibrolamellar and typical hepatocellular carcinomas.
Design: Cases were collected from 4 academic centers. To be sure of the appropriate diagnosis, only full sections from completely resected tumors were evaluated. Control groups included hepatocellular carcinomas arising in both non-cirrhotic livers as well as cirrhotic livers. A group of cholangiocarcinomas were also stained. CD68 immunostaining was scored for both intensity and distribution on a scale of 0 to 3+.
Results: 23 primary fibrolamellar carcinomas and 9 metastases (total of 24 individuals) were immunostained and showed a distinctive granular, dot-like or stippled pattern of cytoplasmic staining in nearly all cases (31/32), with a median distribution and intensity score of 3+. In control hepatocellular carcinomas that arose in non-cirrhotic livers, 10/39 showed CD68 staining with a median distribution and intensity score of 2+. In 4 of these 10 cases, there was a stippled dot-like cytoplasmic staining similar to fibrolamellar carcinomas, while 6 cases showed diffuse cytoplasmic positivity. In hepatocellular carcinomas arising in cirrhotic livers, 3/27 cases showed CD68 positivity, all with stippled dot-like cytoplasmic staining similar to that of fibrolamellar carcinomas. All 5 cholangiocarcinomas were negative. Overall, CD68 positivity was strongly associated with fibrolamellar carcinomas, p<0.001.
Conclusions: Fibrolamellar carcinomas have a distinctive stippled cytoplasmic staining for CD68, likely reflecting increased numbers of cytoplasmic lysosomes. This staining pattern is not specific and can be seen in a subset of typical hepatocellular carcinomas, but the lack of a stippled cytoplasmic pattern would strongly suggest a tumor is not a fibrolamellar carcinoma.
Category: Liver & Pancreas
Tuesday, March 23, 2010 9:30 AM
Poster Session III # 234, Tuesday Morning