Hepatocellular adenoma: what is new in 2008

Abstract

Patients (85%) with hepatocellular adenoma (HCA) are women taking oral contraceptives. They can be divided into four subgroups according to their genotype/ phenotype features. (1) Hepatocyte nuclear factor 1a (HNF1a) biallelic somatic mutations are observed in 35% of the HCA cases. It occurs in almost all cases in women. HNF1a-mutated HCA are most of the time, highly steatotic, with a lack of expression of liver fatty acid binding protein (LFABP) in immunohistochemistry analyses. Adenomatosis is frequently detected in this context. An HNF1a germline mutation is observed in less than 5% of HCA cases and can be associated with MODY 3 diabetes. (2) An activating b-catenin mutation was found in 10% of HCA. These b-catenin activated HCAs are observed in men and women, and specific risk factors, such as male hormone administration or glycogenosis, are associated with their development. Immunohistochemistry studies show that these HCAs overexpress b-catenin (nuclear and cytoplasmic) and glutamine synthetase. This group of tumours has a higher risk of malignant transformation into hepatocellular carcinoma. (3) Inflammatory HCAs are observed in 40% of the cases, and they are most frequent in women but are also found in men. Lesions are characterised by inflammatory infiltrates, dystrophic arteries, sinusoidal dilatation and ductular reaction. They express serum amyloid A and C-reactive protein. In this group, GGT is frequently elevated, with a biological inflammatory syndrome present. Also, there are more overweight patients in this group. An additional 10% of inflammatory HCAs express b-catenin, and are also at risk of malignant transformation. (4) Currently, less than 10% of HCAs are unclassified. It is hoped that in the near future it will be possible with clinical, biological and imaging data to predict in which of the 2 major groups (HNF1a-mutated HCA and inflammatory HCA) the patient belongs and to propose better guidelines in terms of surveillance and treatment.

Hepatocellular adenoma associated with familial adenomatous polyposis coli

“…Our patient showed no symptoms or signs of an inflammatory syndrome. Additionally, the HCA in the present case morphologically lacked the typical characteristics of I-HCA, such as inflammatory infiltrates, sinusoidal dilatation and numerous thick arteries [21][22][23] . The β -catenin gene was supposed to be normal [24,25] because β -catenin was immunohistochemically detected only around the cytomembrane, without aberrant nuclear and cytoplasmic staining distributed in random and heterogeneous patterns ( Figure 3D).…”

“…Recently, genotype/phenotype classifications of HCA have drawn attention as a noticeable phenomenon from the aspects of pathogenesis and pathological tumorigenesis [21][22][23] . In their reports, HCAs are classified into four categories: (1) HCAs with mutations of the HNF1 gene (H-HCA, 35%-40%); (2) HCAs with mutations of the β -catenin gene (β-HCA, 10%-15%); (3) inflammatory HCAs with mutation of the IL6ST gene (I-HCA, 40%-50%); and (4) HCAs without markers (unclassified HCA, less than 5%-10%).…”

Hepatocellular adenoma: An update

“…Hepatocellular proliferations noted in these lesions are secondary to sustained activation of janus kinase (involved in the JAK-STAT pathway). It is characterized by inflammatory changes such as sinusoidal dilatation, dystrophic arteries and dystrophic vessel ductular reaction and immunohistochemically positivity for serum amyloid A and C reactive protein [13] . It is more common in females on OCPs, but has also been associated with obesity and alcohol abuse.…”

“…Telangiectatic hepatocellular adenoma which was once referred as telangiectatic focal nodular hyperplasia has now been reclassified under inflammatory HCA. Ten percent of these HCAs have been reported to harbour mutations in the β-catenin gene are hence also at danger of malignant changes; and (4) Unclassified Adenomas: The unclassified type (< 10%) includes patients whose tumors did not exhibit genetic or inflammatory diseases [13] . It usually is a diagnosis of exclusion.…”

Indicação e tratamento dos tumores benignos do fígado

“…T he liver tumors are very common occurring in 9% of the population, but, fortunately, most are benign, asymptomatic and found accidentally on imaging 1,2,3,4,5 . However, malignant tumors are serious and are increasing in incidence.…”