Atypical Hepatocellular Neoplasms: Review of Clinical, Morphologic, Immunohistochemical, Molecular, and Cytogenetic Features

The distinction of hepatocellular adenoma from well-differentiated hepatocellular carcinoma (HCC) can be difficult in some cases, especially on biopsy specimens. These borderline cases often occur in men or older patients and may have β-catenin activation or focal atypical morphologic features (such as small cell change, prominent pseudoacinar formation, cytologic atypia, focally thick plates, and/or focal reticulin loss) that are insufficient for an unequivocal diagnosis of HCC. The term "atypical hepatocellular neoplasm" has been advocated for these tumors, but a number of other terms, including "atypical adenoma," "hepatocellular neoplasm of uncertain malignant potential," and "well-differentiated hepatocellular neoplasm with atypical or borderline features" have also been proposed. This review proposes guidelines for designating tumors as atypical hepatocellular neoplasm and describes clinical, morphologic, immunohistochemical, molecular, and cytogenetic features that distinguish these tumors from typical hepatocellular adenoma and HCC.

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