Pathologic Diagnosis of Well-differentiated Hepatocellular Lesions: A Practical Approach to Diagnosis With Particular Focus in Core Needle Biopsies and Utilization of Ancillary Techniques

Common well-differentiated hepatocellular lesions include focal nodular hyperplasia, focal nodular hyperplasia–like lesions, large regenerative nodule, hepatocellular adenoma, dysplastic nodule, and hepatocellular carcinoma. The term atypical hepatocellular neoplasm/hepatocellular neoplasm of uncertain malignant potential can be used especially in needle core biopsies when a well-differentiated hepatocellular lesion is either histologically atypical (focal reticulin loss, focal cytologic/architectural atypia) or is clinically atypical (male sex or female >50 y) and cannot be confidently classified as adenoma or hepatocellular carcinoma. These are resected in an attempt for more definite classification. Although radiology can suggest the diagnosis in some of the entities mentioned above, needle core biopsies are often performed to confirm the diagnosis and plan therapy. Diagnosis of these lesions on needle core biopsies can be challenging and may have overlapping histologic and sometimes even immunohistochemical features. Herein, we review the histologic, immunohistochemical, and molecular features of well-differentiated hepatocellular lesions, along with recent advances in this area. We also provide the best approach for the diagnosis of well-differentiated hepatocellular lesions with ancillary testing, especially on needle core biopsies, and discuss the pitfalls. Accurate recognition of well-differentiated hepatocellular lesions is essential as some of them have excellent prognosis and may not require resection, while others have histologic prognostic information that is key for management.