What is the role of immunohistochemistry in the workup of hepatocellular adenoma (HCA)?

Updated: Feb 21, 2018
  • Author: Bradford A Whitmer, DO; Chief Editor: BS Anand, MD  more...
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It may be reasonable to perform immunohistochemistry to further characterize the lesion under the new Bordeaux classification of HCA currently being evaluated. This subclassification includes hepatocyte nuclear factor 1α-inactivated HCA (HNF1α HCA 30-35%), β-catenin-mutated HCA (β-cat HCA 10-15%), inflammatory HCA (50%), and a subgroup of less than 10% that remains unclassified. Ten percent of inflammatory HCA can also be β-cat mutated. [12]

Glutamine synthetase staining may be useful in differentiating β-catenin-activated HCA and focal nodular hyperplasia owing to differences in their staining patterns. Focal nodular hyperplasia has a maplike distribution that is distant from fibrous bands or arteries, while β-catenin-activated HCAs have a more diffuse staining pattern. [43, 44]

Although HCAs may transform into HCC, the AFP is an insensitive test for HCC screening, yet few other tests are available. Zucman-Rossi et al classified 96 HCAs by sequencing the genes coding for HNF1α and β-cat. [45] The investigators reported that HCC is found in 46% of β-cat–mutated tumors, whereas they are rarely found in HNF1α tumors or tumors that lack β-cat or HNF1α.

Tumor cell expression patterns of E-cadherin and matrix metalloproteinases -1,-2,-7 and -9 were studied in a variety of liver tumors and controls by Tretiakova et al. [46] The investigators reported that hepatocellular adenoma was characterized by an absence of matrix metalloproteinase-7 expression, whereas HCC without cirrhosis had low metalloproteinase-9 expression.

Glycipan-3 (GPC3) is a cell surface glycoprotein that is overexpressed in HCCs. Wang reported that GPC3 staining was not present in all 110 cases of benign liver tumors in their study, yet the staining was positive in 75.7% of HCCs. [47]

Agrin is a proteoglycan component of bile duct and vascular basement membranes of the liver and is deposited in microscopic blood vessels of HCC. Tatrai et al reported that the combination of immunohistochemical staining for agrin and CD34 was helpful for differentiating HCC from benign lesions when the diagnosis was equivocal. [48] In addition, agrin appeared to be more sensitive than GPC-3, as agrin is diffusely deposited in all malignant lesions, whereas GPC-3 may only be present in a few cells.

Ahmad reported that a combination of cytokeratin 7 and 9 with neuronal cell adhesion molecule immunostains were very helpful in differentiating normal liver tissue from tumors and also in differentiating hepatocellular adenomas from FNH. [49]

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