Update: Radiologic-Pathologic Correlation of Hepatocellular Adenoma

Sadhna Dhingra MD, FCAP; Chakradhar Thupili, MD; Steven Chua, MD, PhD; Kaustubh Shirlakar MD; Srinivasa R Prasad, MD; Venkateswar R Surabhi, MD


Appl Radiol. 2019;48(6):21-29. 

In This Article


Hepatocellular adenoma (HA) was considered a homogeneous entity until the early 2000s, when a French group of clinical researchers demonstrated somatic bi-allelic mutations of transcription factor 1 (TCF 1) gene encoding hepatocyte nuclear factor 1 (HNF 1) in a subset of HAs.[20] Subsequently, they reported that telangiectatic focal nodular hyperplasias (T-FNHs) are monoclonal lesions and clinically behave similar to HAs without HNF-1-α mutation.[21] These were later classified as inflammatory HAs.[22] Ongoing genomic studies of HAs by the same French group led to the landmark paper in 2006 that introduced the genotype-phenotype taxonomy of HAs.[22] According to this schemata, the HAs are classified into 4 subtypes, of which the first three have unique molecular signatures as well as histological, immunophenotypical and radiological features.[7] These were: 1. HNF-1-α (HNF 1A) mutated HAs; 2. β-catenin mutated HAs; 3. Inflammatory-type HAs. The last group classified as "unclassified" refers to HAs that do not satisfy the diagnostic criterion described in the three other subtypes (Table 1). Using sequencing and gene expression profiling, this classification has further been refined recently to include 6 subgroups of HAs.[9,1,23] The β-catenin mutated HAs (BHA and IHA with β-catenin mutations) are further split into: (a) BHA with exon 3 mutations; (b) BHA with exon 7/8 mutations. A subset of unclassified HA has been found to show constitutive activation of sonic hedgehog (shh) pathway due to overexpression of GLI family zinc finger 1 (GLI1). These HAs are associated with a higher risk of bleeding. They do not have specific morphological features or immunoexpression profiles.

We will focus on four subtypes of HAs in this review, as radiologic features of the newer subtypes are not well defined. Clinical implementation of this classification in diagnostic medicine has brought about a paradigm shift in the management of HAs, as this helps determine the potential for complications including bleeding and malignant transformation, and thereby guide further management in terms of resection and/or surveillance.