Hepatocellular adenomas: recent updates

Abstract

Hepatocellular adenoma (HCA) is a heterogeneous entity, from both the histomorphological and molecular aspects, and the resultant subclassification has brought a strong translational impact for both pathologists and clinicians. In this review, we provide an overview of the recent updates on HCA from the pathologists' perspective and discuss several practical issues and pitfalls that may be useful for diagnostic practice.

Keywords: Classification; Hepatocellular adenoma; Pathology.

Fig. 1

Inflammatory hepatocellular adenoma. Sinusoidal dilatation, congestion and peliosis is seen in the tumor (A–C). Inflammatory cell infiltration (C), thick arteriolar structures with ductular reaction, resembling portal tracts (“pseudo-portal tracts”) and steatosis (D) may be seen in these tumors. Diffuse steatosis may be seen in the background liver (A). The tumor cells express serum amyloid A (E; inset: granular cytoplasmic staining in tumor cells) and C-reactive peptide (F).

Fig. 2

β-catenin–activated hepatocellular adenoma (B-HCA). There is mild trabecular thickening (A) and pseudoglandular structures (B, C). Mild cytological atypia is present (A–C). Cholestasis may be seen (C). On immunohistochemistry, B-HCA with strong β-catenin activation (Bex3-HCA) demonstrates nuclear β-catenin expression (D), instead of the normal membranous pattern (inset), and diffuse homogeneous glutamine synthetase expression is seen in such tumors (E, inset: higher-power view).

Fig. 3

Immunohistochemical correlates of CTNNB1 alteration status in β-catenin-activated HCA, FNH and normal liver. FNH, focal nodular hyperplasia; HCA, hepatocellular adenoma. ^aSerum amyloid A and/or reactive peptide is additionally expressed in β-catenin-activated inflammatory HCA.

Fig. 4

HNF1A-inactivated hepatocellular adenoma. Diffuse steatosis is seen in the tumor, compared to the surrounding hepatic parenchyme (A–C). There is no significant cytological or architectural atypia on higher-power magnification (B). Immunohistochemically, the tumor displays loss of liver fatty acid-binding protein expression (C) (dotted line: tumor).

Fig. 5

Atypia in hepatocellular neoplasms. When features atypical for hepatocellular adenomas, such as frequent pseudoglandular structures (A, C–E), nuclear atypia (B, C) and focal reticulin loss (D; inset: preserved reticulin framework for comparison), are identified, the differential diagnosis should be between atypical hepatocellular neoplasm and well-differentiated hepatocellular carcinoma. When these features are only focally present (< 5%), the terminology of atypical hepatocellular neoplasm may be used. Nuclear β-catenin expression is often identified in such cases (E).

Fig. 6

Focal nodular hyperplasia. A typical low power view of a resected case (A). A central stellate scar with radiating fibrous septa is seen, containing multiple irregular-shaped vascular structures. When needle biopsy specimens are obtained from the central scar or fibrous septa (B, C), it is easy to identify the abnormal vascular channels with varying calibers, shape and irregular walk thickness. Sometimes biopsies include the peripheral portions without the obvious vascular anomalies; instead there is at least mild hepatocellular nodularity with ductular reaction (D). Glutamine synthetase immunohistochemistry demonstrates broad bands of GS-expressing hepatocytes (E), which corresponds to the map-like pattern in Fig. 3, in contrast to the normal perivenular pattern (arrows).