Benign hepatocellular lesions and neoplasms: a comprehensive review

Abstract The prevalence of benign mass-forming liver lesions has significantly increased in recent years due to advances in diagnostic imaging. In general, these lesions can be either neoplastic or nonneoplastic and carry a different prognosis and management. Among benign mass-forming lesions of the liver, hemangiomas are the most common, followed by focal nodular hyperplasia, which is encountered ten times more frequently than adenomas. Hepatocellular adenomas are the third most common benign tumor of the liver. Their classification was revised in 2016 based on histomorphology and molecular signatures and includes hepatocyte nuclear factor-1 alpha (HNF1A)-mutated hepatocellular adenomas, beta-catenin 1 (CTNNB1) gene–mutated hepatocellular adenomas, interleukin-6 signal transducer gene–mutated or inflammatory/telangiectatic hepatocellular adenomas, and unclassified hepatocellular adenomas. Since then, a new subtype has been discovered, decreasing the proportion of unclassified cases. Hepatocellular adenomas have different molecular characteristics, behavior, and management, depending on the subtype. The telangiectatic subtype tends to bleed and may cause hemoperitoneum whereas the beta-catenin mutated subtype can progress to malignancy and is surgically resected independent of the size or symptoms. Other hepatic lesions include nodular regenerative hyperplasia, which occurs in the setting of blood flow alterations; and focal fatty change or benign steatotic nodules. Lastly, epithelioid angiomyolipomas are very uncommon benign mesenchymal liver tumors that belong to a family of tumor arising from perivascular epithelioid cells (PEComas) either sporadically or in the setting of tuberous sclerosis. Herein, we review these benign hepatic lesions and neoplasms and discuss the histomorphology and immunohistochemistry that allow us to render a specific diagnosis.