Hepatocellular carcinoma (HCC) can be difficult to distinguish from its mimics, including metastatic tumor, benign hepatocellular lesion, and high-grade dysplastic nodule, especially when limited biopsy material is available. Hence, the judicious use of immunohistochemical stains is necessary to establish a correct diagnosis. This article describes advantages and disadvantages of immunohistochemical markers that are most commonly used to distinguish between these lesions. Diagnostic workup of malignant liver mass (HCC and its histologic variants vs metastatic tumor) as well as well-differentiated hepatocellular lesion (well-differentiated HCC vs focal nodular hyperplasia vs hepatocellular adenoma) is also discussed.
Key points
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In most situations, hepatocellular carcinoma (HCC) can be distinguished from metastatic tumor by using a panel of 2 hepatocellular (arginase-1, with Hep Par-1 or glypican-3) and 2 markers more commonly positive in adenocarcinoma (CK19 and MOC-31).
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A 2-stain approach using arginase-1 and CK19 can be a useful starting point if limited tissue is available.
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Use of less sensitive hepatocellular markers like polyclonal CEA and alpha-fetoprotein should be avoided for routine use and should be reserved for challenging cases. Similarly, use of large reflex panels of site-specific markers should be avoided.
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A panel of glutamine synthetase, β-catenin, and reticulin stains can help in differentiation of benign hepatocellular lesions from well-differentiated HCC. Additional stains like serum amyloid A, C-reactive protein, and liver-fatty acid binding protein can be obtained to subclassify hepatocellular adenoma.
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