Hepatocellular Carcinoma in Noncirrhotic Livers: Morphology, Immunophenotype, and Clinical Outcome.
Ta-Chiang Liu, Neeta Vachharajani, William C Chapman, Elizabeth M Brunt. Washington University School of Medicine, St. Louis, MO
Background: The majority of hepatocellular carcinomas (HCC) arise in the setting of cirrhosis, from an established sequence of premalignant events; liver cell adenomas (LCA) arise in a hormonally or metabolically stimulated liver. Less is understood regarding the pathogenesis of non-cirrhotic (NC) HCC.
Design: Forty consecutive resected or transplanted cases of NC-HCC between 1997 and 2009 were collected. Routine and immunohistochemical (IHC) stains for p53, keratin (K) 19, β-catenin, glutamine synthetase (GS), glypican-3 (GPC-3), and liver fatty acid binding protein (LFABP) were analyzed. Tumor grading was by Edmondson-Steiner (E-S) criteria.
Results: Among the 40 patients, 26 (65%) were men; the mean age at surgery was 66 yrs (range 18 to 77 yr). 34 (85%) had no evidence of liver disease; 2 (5%) had HBV, 3 (7.5%) HCV, 1 (2.5%) had both HBV and HCV. Two (2.5%) with chronic hepatitis also had alcoholic liver disease. Eight (20%) patients were diabetic and 11 (27.5%) were obese. None had cirrhosis. The average tumor size was 7.2 cm (mean 1.5 – 19cm). Seven (17.5%) were E-S grade 1 and had vascular ectasias similar to adenomas; 28 (70%) were grade 2, 2 (5%) were grade 3, and 3 (7.5%) were grade 4. Three cases (7.5%) showed features of combined HCC-cholangiocarcinoma, and two (5%) showed > 50% clear cell changes. Nine cases (22.5%) showed strong nuclear p53 staining in >10% tumor cells. K19 was detected in 7 (17.5%). The majority of the cases showed diffuse cytoplasmic expression of GS (95%), but did not express nuclear β-catenin (95%). Patchy cytoplasmic expression of GPC-3 was seen in 16 (40%), whereas diffuse expression was seen in 11 (27.5%); 13 (32.5%) were negative. Various patterns of LFABP were observed in 23 cases (57.5%). Seventeen patients (42.5%) developed recurrence. The overall survival was 3.5 yrs following surgery. Of all factors, only strong p53 stain correlated with shortened survival by univariate analysis (p<0.05).
Conclusions: In this group of 40 noncirrhotic HCC, there was a slight male predominance. Chronic viral hepatitis and/or alcoholism were identified in < 20% of cases; obesity and DM were not features of significance in aggressive behavior. The majority of tumors were E-S grade 2, however, many encapsulated grade 1 NC-HCCs were suggestive of LCA. K19 expression, a marker of aggressive behavior in cirrhotic HCC, was detected in <20% of cases, and only increased nuclear p53 expression correlated with poor outcome.
Category: Liver & Pancreas
Tuesday, March 1, 2011 9:30 AM
Poster Session III # 261, Tuesday Morning