Changing trends in malignant transformation of hepatocellular adenoma

Farges, Olivier; Ferreira, Nélio Reis; Dokmak, Safi; Belghiti, Jacques; Bédossa, Pierre; Paradis, Valérie

doi:10.1136/gut.2010.222109

Cited by 274 publications

(225 citation statements)

References 32 publications

Supporting

Mentioning

205

Contrasting

Unclassified

Order By: Relevance

“…This risk in men is unlikely to be entirely explained by the presence of pigment, as men with hepatocellular adenomas have a generalized increase risk of malignancy, which in some studies exceeds 10 times that of women. 20,21 Our findings, however, suggest that this risk is even higher in males with pigmented neoplasms.…”

Section: Discussioncontrasting

confidence: 53%

Pigmented hepatocellular adenomas have a high risk of atypia and malignancy

et al. 2015

View full text Add to dashboard Cite

Pigment deposition is occasionally seen in hepatocellular adenomas. Several reports suggest that pigmented hepatocellular adenomas have increased risk of malignancy, but these tumors remain incompletely understood. To determine the frequency of pigment deposition, we evaluated and classified 109 well-differentiated hepatocellular neoplasms that were originally diagnosed or submitted in consultation as hepatocellular adenomas and found 27 (25%) pigmented tumors. All were negative on iron stain and in three cases electron microscopy confirmed the pigment was lipofuscin. The lipofuscin intensely stained with glypican-3 in most cases (89%). Of the 27 pigmented tumors, 11 cases (41%) were classified as hepatocellular adenomas, 7 cases (27%) were classified as atypical hepatocellular adenomas/hepatocellular neoplasms of uncertain malignant potential, and 9 cases (33%) were reclassified as well-differentiated hepatocellular carcinomas. Four (of 9) hepatocellular carcinomas arose in pigmented hepatocellular adenomas, giving a rate of malignant transformation in pigmented hepatocellular adenomas of 27%. Of the total 27 pigmented tumors, 78% were in women and 22% in men, but interestingly only men had tumors classified as hepatocellular carcinoma or hepatocellular neoplasm of uncertain malignant potential. Also of note, a total of 10 individuals (37%) had multiple hepatocellular neoplasms but in 9 of these cases the other adenomas were non-pigmented. Importantly, in cases with multiple hepatocellular neoplasms, only the pigmented hepatocellular neoplasms had atypia or malignancy. Genotype-phenotype classification of the pigmented tumors showed different subtypes: HNF1α inactivated (48%), β-catenin activated (26%), inflammatory (15%), concurrently β-catenin activated and inflammatory in 1 hepatocellular adenoma, concurrently HNF-1α inactivated and β-catenin activated in 1 hepatocellular adenoma, and unclassified in 1 hepatocellular carcinoma. In conclusion, hepatocellular adenomas with lipofuscin pigment are a heterogeneous group of adenomas, with HNF-1α inactivation being the commonest genotype. They have an increased risk of atypia and malignancy, especially in males.

show abstract

Section: Discussioncontrasting

confidence: 53%

Pigmented hepatocellular adenomas have a high risk of atypia and malignancy

et al. 2015

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 99%

“…The associated factors in inflammatory hepatocellular adenomas included alcohol use, tobacco use, elevated BMI (obesity), and fatty liver disease; 2,3,12 therefore, this 14 have recently reported changing trends in the malignant transformation of hepatocellular adenoma. The prevalence of malignancy in hepatocellular adenoma was 10 times more frequent in men than in women in their study, 14 and they propose that management of hepatocellular adenoma should primarily be based on gender. Although oral contraception is a classical cause of hepatocellular adenoma in women but a marginal cause of hepatocellular carcinoma, metabolic syndrome appears to be an emerging condition associated with malignant transformation of hepatocellular adenoma in men, and is the likely predisposing condition for hepatocellular carcinoma in this setting.…”

Section: Discussionmentioning

confidence: 99%

A serum amyloid A-positive hepatocellular neoplasm arising in alcoholic cirrhosis: a previously unrecognized type of inflammatory hepatocellular tumor

et al. 2012

View full text Add to dashboard Cite

Hepatocellular adenoma usually arises in the absence of significant fibrosis. Herein, we report seven patients with serum amyloid A-positive hepatocellular neoplasm, which shares features with inflammatory hepatocellular adenoma arising in alcoholic cirrhosis. Seven patients (two women and five men, age range 41-67 years) with hypervascular hepatocellular nodules associated with alcoholic cirrhosis were retrieved from our pathological files (1997)(1998)(1999)(2000)(2001)(2002)(2003)(2004)(2005)(2006)(2007)(2008)(2009)(2010)(2011). The hepatocellular nodules were multiple (43) in all patients and 17 nodules were histologically examined. We surveyed the immunoreactivity for serum amyloid A, glutamine synthetase, and glypican-3 in the hepatocellular nodules and control lesions, including 5 focal nodular hyperplasia, 18 dysplastic nodules, and 54 hepatocellular carcinomas in various background diseases. In all, 15 of 17 nodules showed strong and distinct immunoreactivity for serum amyloid A, sharing features with inflammatory hepatocellular adenoma. The serum amyloid A-positive hepatocellular neoplasms showed increased cellular density, inflammatory infiltrate, sinusoidal dilatation, and ductular reaction to various degrees. Although about a half of dysplastic nodules and hepatocellular carcinomas showed focal immunoreactivity for serum amyloid A, the extent of serum amyloid A expression was significantly higher in serum amyloid A-positive hepatocellular neoplasms, than in control nodules. The serum amyloid A-positive hepatocellular neoplasms did not show the overexpression of glutamine synthetase or immunoreactivity for glypican-3. In contrast, most hepatocellular carcinomas showed the overexpression of glutamine synthetase and immunoreactivity for glypican-3, irrespective of background diseases. In conclusion, this study highlights a characteristic group of hepatocellular neoplasms arising in alcoholic cirrhosis, which share features with inflammatory hepatocellular adenomas. These serum amyloid Apositive hepatocellular neoplasms may be a new type of inflammatory hepatocellular tumors in alcoholic patients.

show abstract

“…3,5 Beta-catenin-mutated hepatocellular adenomas (15-20%) are characterized by CTNNB1-activating mutations responsible for constitutive Wnt/Beta-catenin pathway activation. 2,6 This subgroup has the higher risk of malignant transformation, 3,6,7 and microscopic examination may demonstrate moderate atypia. 2,5 The third group of hepatocellular adenoma, namely inflammatory adenoma (about 50% of all hepatocellular adenomas), harbor somatic gain-offunction mutations in either IL6ST, FRK, JAK1, STAT3, or GNAS genes activating the interleukin-6/ JAK/STAT pathway.…”

mentioning

confidence: 99%

Inflammatory hepatocellular adenomas developed in the setting of chronic liver disease and cirrhosis

et al. 2016

View full text Add to dashboard Cite

Hepatocellular adenoma is considered to occur exclusively in non-fibrotic livers. It is a heterogeneous entity and a molecular classification is now widely accepted. The most frequent hepatocellular adenoma subtype, namely inflammatory adenoma, harbor somatic activating mutations of genes involved in the interleukin-6 pathway that lead to high C-reactive protein and serum amyloid A expression. The aim of our study was to investigate a series of benign hepatocellular neoplasms developed on cirrhotic livers and characterized by an unequivocal histological diagnosis. We performed a clinical, pathological, and molecular study of 10 benign hepatocellular neoplasms developed in three patients with cirrhosis. Markers allowing hepatocellular adenoma classification were assessed by quantitative real-time PCR and immunohistochemistry. Samples were sequenced for CTNNB1, HNF1A, IL6ST, GNAS, STAT3, and TERT (promoter) mutations. A control series of 32 classical macronodules developed in cirrhosis related to various etiologies was screened by immunohistochemistry and gene sequencing. The three patients had cirrhosis related to metabolic syndrome and/or alcohol intake; two had a single tumor, while the third developed more than 30 lesions. Microscopic examination showed welldifferentiated neoplasms sharing features with inflammatory adenoma including inflammatory infiltrates, sinusoidal dilatation, and dystrophic vessels. Sequencing revealed classical hotspot somatic mutations (IL6ST, n = 8; STAT3, n = 1; and GNAS, n = 1) known to be responsible for IL-6/JAK/STAT pathway activation. Two classical high-grade macronodules demonstrated high serum amyloid A and/or C-reactive protein expression, without gene mutations. Altogether, our findings support the existence of rare inflammatory adenoma developed in cirrhosis.

show abstract

Changing trends in malignant transformation of hepatocellular adenoma

Cited by 274 publications

References 32 publications

Pigmented hepatocellular adenomas have a high risk of atypia and malignancy

Pigmented hepatocellular adenomas have a high risk of atypia and malignancy

A serum amyloid A-positive hepatocellular neoplasm arising in alcoholic cirrhosis: a previously unrecognized type of inflammatory hepatocellular tumor

Inflammatory hepatocellular adenomas developed in the setting of chronic liver disease and cirrhosis

Contact Info

Product

Resources

About