Immunophenotypic Subtypes of Hepatic Adenomas in a Large Tertiary Care Center in the United States
Elizabeth McMillen, Stephen Lagana, Fei Bao. Columbia University Medical Center, New York, NY
Background: Hepatic adenomas (HAs) are benign tumors with the capacity for malignant transformation. A classification scheme for HAs was recently proposed by Bioulac-Sage et. al. Three subtypes of HAs were identified based on molecular and immunophenotypic characteristics: inflammatory type (IHA) with Serum Amyloid A overexpression, steatotic type correlated with hepatic nuclear factor (HNF) 1A mutation (SHA), and beta-catenin-mutated subtype with upregulation of glutamine synthetase (bHA). The bHA subtype has a higher risk of transformation into hepatocellular carcinoma, and so detection of this subtype provides important prognostic information.
Design: We identified 30 cases of hepatic adenomas in our archives from 1994 to 2011, sampled from 27 patients. Three patients had both biopsies and resections, eight patients had only biopsies, and 16 had only resections. Immunohistochemistry (IHC) was performed on paraffin sections with the following 3 antibodies: anti-liver fatty acid binding protein (LFABP), anti-glutamine synthetase (GS) and anti-Serum amyloid A (SAA). Subtype classification was analyzed based on H&E morphology. The staining of IHC was scored from 0-2, with 0 being 0-9% staining, 1 being 10-50% staining in the neoplastic cells, and 2 being >50% in neoplastic cells. Immunosubtyping of HAs based on IHC results was performed and compared to the morphological subtypes.
Results: There were 21 females (ages 6-75) and 6 males (ages 24-66) in our cohort. Eleven patients had multiple adenomas. The adenomas averaged 8.7cm in greatest dimension. On morphology, 11 were classified as bHAs, 9 as IHAs, and 10 as SHAs. For patients with multiple adenomas, 3 showed bHA, 3 IHA, and 5 SHA phenotypes. All HAs were positive for at least one IHC marker. GS was positive in 9 out of 11 bHAs (81%), it was also seen in 4 out of 9 IHAs. SAA staining was positive in 8 out of 9 (89%) IHAs, but some degree of staining was also observed in 7 of 11 (64%) of bHA, with 2 having focal and 5 diffuse staining. LFABP expression was lost in 8 of 10 (80%) SHA subtype.
Conclusions: LFABP, GS and SAA were highly sensitive immunomarkers for diagnosing SHA, bHA and IHA subtypes, respectively, and may be useful in confirming morphologic diagnosis. Furthermore, 64% bHA stained positively for SAA and the majority of these lesions had atypical features (4 out of 5 cases). The behavior of these “overlap” lesions should be studied further, as they have characteristics of both bHA and IHA. Molecular analysis may help further define these cases with both GS and SAA overexpression.
Tuesday, March 20, 2012 9:30 AM
Poster Session III # 255, Tuesday Morning