the Management of Benign Liver Lesions

Hemangioma:

Hemangiomas are the most common benign non-cystic liver lesions, occurring in up to 20% of the population, with a reported preponderance in women at a 4:1 ratio. They are benign mesenchymal vascular lesions consisting of clusters of blood- filled cavities lined by endothelial cells, ranging in size from a few millimeters to greater than 20 cm. Hemangiomas are believed to arise from a congenital abnormality in vasculogenesis, growing slowly from birth. Increase in size of hemangiomas can occur and is favored to be due to progressive ectasia of the vasculature and not related to hypertrophy of the lesion, ⁽¹⁾.

Focal nodular hyperplasia:

FNH is the second most common solid liver lesion, with 0.3%–3% of people having FNH on autopsy. FNH is favored to arise as a local reaction to vascular abnormalities, specifically aberrant hemodynamics within the liver, usually secondary to an aberrant dystrophic artery or a vascular injury, resulting in a disturbance of local blood flow, which can result in hyper-perfusion, oxidative stress from hypoxia, and hepatic stellate cell response, all of which result in a hyperplastic microenvironment and FNH development, ⁽²⁾.

Hepatocellular adenoma:

HCAs represent a benign proliferation of mature hepatocytes, which can develop in a background of an otherwise normal liver, or one affected by steatosis or glycogenosis. This tumor is usually well-defined but rarely encapsulated, highly vascular, variable in size, and solitary or multifocal. The presence of multifocal nodules has been defined as adenomatosis, ⁽³⁾.

HCA molecular classification, ⁽⁴⁾:

Based on genomic analysis, three main molecular subtypes of HCA have been clearly identified so far, with a fourth class presently uncharacterized.

1.      HCA inactivated for HNF-1a (H-HCA), accounting for 30 to 40% of HCA.H-HCA are defined by inactivation of HNF-1a, a transcription factor involved in hepatocyte differentiation and metabolism control. Morphologically, H-HCAs are characterized by prominent steatosis.

2.      Inflammatory adenomas (I-HCA), accounting for 40 to 55% of HCA. I-HCAs represent a heterogeneous subgroup of HCA regarding the variety of gene mutations, I-HCA are more often observed in patients with obesity and/or metabolic syndrome, as well as in the context of a high alcohol consumption. Systemic inflammatory syndrome, demonstrated by increased serum C-reactive protein (CRP) and fibrinogen levels, can regress following HCA removal. Morphologically, I-HCA, initially described as ‘‘telangiectatic form of FNH”, are characterized by the presence of clusters of small arteries surrounded by extracellular matrix and inflammatory infiltrates associated with foci of sinusoidal dilatation.

3.      β-catenin activated HCA (β-HCA), accounting for 10 to 20% of HCA. β-HCA are defined by β-catenin activation within the tumours. β-HCA are over represented in males and display a higher risk of malignant transformation towards hepatocellular carcinoma (HCC). Morphologically, β-HCAs are characterized by the presence of cellular atypias, pseudoglandular formations and cholestasis.

4.      Unclassified HCA, accounting for 5% to 10% of HCA.  A small subset of HCA do not display any specific morphological features nor do they have any of the gene mutations previously described.

Hepatic cysts:

Hepatic cysts are thin-walled structures lined by cuboidal bile duct epithelium and filled with isotonic fluid.  They are the result of ductal plate malformation without communication with the biliary tree, ⁽⁴⁾.