Borderline Hepatocellular Adenomas: A Practical Diagnostic Approach Based on Pathologic and Molecular Features

Area of Science:

• Hepatobiliary pathology
• Molecular diagnostics
• Surgical oncology

Background:

• Borderline hepatocellular adenomas (BL-HCA) present diagnostic challenges due to ambiguous features between benign adenomas and malignant hepatocellular carcinoma (HCC).
• The malignant potential of BL-HCA remains debated, necessitating further investigation into their biological behavior.

Purpose of the Study:

• To compare clinicopathologic and molecular characteristics of BL-HCA with typical HCA (T-HCA), HCC on HCA, and HCC.
• To assess the risk of malignancy in BL-HCA by evaluating molecular markers and clinical features.

Main Methods:

• Retrospective analysis of 106 liver resection specimens (39 BL-HCA, 42 T-HCA, 12 HCC on HCA, 13 HCC).
• Somatic mutation analysis (TERT promoter) and gene expression profiling (96 genes) on frozen and formalin-fixed samples.
• Clinical data review including patient demographics, tumor size, and recurrence.

Main Results:

• BL-HCA patients were predominantly female (69%) with a median age of 37 years; tumors averaged 7.5 cm, and no recurrence was observed.
• BL-HCA showed significant enrichment in beta-catenin mutations compared to T-HCA (41% vs 6%, P < .001).
• Gene expression analysis revealed BL-HCA molecularly overlaps with T-HCA and HCC on HCA, while TERT promoter mutations were exclusive to HCC on HCA and HCC.

Conclusions:

• BL-HCA exhibit clinicopathologic and molecular profiles more aligned with T-HCA than with malignant HCC.
• Morphologic and molecular analyses are crucial for accurate BL-HCA diagnosis and management strategies.
• BL-HCA do not appear to possess the malignant molecular drivers (TERT promoter mutations) seen in HCC.