Hepatocellular Benign Tumors—From Molecular Classification to Personalized Clinical Care

Nault, Jean–Charles; Bioulac‐Sage, Paulette; Zucman–Rossi, Jessica

doi:10.1053/j.gastro.2013.02.032

Cited by 255 publications

(259 citation statements)

References 153 publications

(226 reference statements)

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“…The risk of malignancy was clearly overestimated in the group with GSD because the literature considers this underlying disease as a risk factor for the MT of adenomas. (8) These data are supported by a high frequency of b-CAT-mutated adenomas (5,7) in this pathology. NOTE: Data are given as n (%).…”

Section: Chiche Et Al Liver Transplantation April 2016supporting

confidence: 62%

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Liver transplantation for adenomatosis: European experience

et al. 2016

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The aim of this study was to collect data from patients who underwent liver transplantation (LT) for adenomatosis; to analyze the symptoms, the characteristics of the disease, and the recipient outcomes; and to better define the role of LT in this rare indication. This retrospective multicenter study, based on data from the European Liver Transplant Registry, encompassed patients who underwent LT for adenomatosis between January 1, 1986, and July 15, 2013, in Europe. Patients with glycogen storage disease (GSD) type IA were not excluded. This study included 49 patients. Sixteen patients had GSD, and 7 had liver vascular abnormalities. The main indications for transplantation were either a suspicion of hepatocellular carcinoma (HCC; 15 patients) or a histologically proven HCC (16 patients), but only 17 had actual malignant transformation (MT) of adenomas. GSD status was similar for the 2 groups, except for age and the presence of HCC on explants (P = 0.030). Three patients with HCC on explant developed recurrence after transplantation. We obtained and studied the pathomolecular characteristics for 23 patients. In conclusion, LT should remain an extremely rare treatment for adenomatosis. Indications for transplantation primarily concern the MT of adenomas. The decision should rely on morphological data and histological evidence of MT. Additional indications should be discussed on a case‐by‐case basis. In this report, we propose a simplified approach to this decision‐making process.

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Section: Chiche Et Al Liver Transplantation April 2016supporting

confidence: 62%

“…(4)(5)(6)(7)(8)(9)(10) However, this surgical approach can be difficult or impossible in cases of LA due to the large number of adenomas. Therefore, liver transplantations (LTs) have been reported in the literature.…”

Section: Liver Transplantation 22 516-526 2016 Aasldmentioning

confidence: 99%

Liver transplantation for adenomatosis: European experience

et al. 2016

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“…1 Recent molecular studies have shown that hepatocellular adenoma is a heterogenous entity, and a molecular classification comprising four subgroups has been proposed, and is now widely accepted. 2,3 The first group of hepatocellular adenoma (30% of all hepatocellular adenoma) is defined by bi-allelic, inactivating mutations of a transcription factor involved in liver differentiation and metabolism, HNF1A (hepatocyte nuclear factor 1A). 4 HNF1A-inactivated hepatocellular adenomas are histologically usually characterized by a massive steatosis in the tumor.…”

mentioning

confidence: 99%

“…4 HNF1A-inactivated hepatocellular adenomas are histologically usually characterized by a massive steatosis in the tumor. 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.…”

mentioning

confidence: 99%

“…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.…”

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confidence: 99%

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

et al. 2016

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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.

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Benign Tumors, Nodules, and Cystic Diseases of the Liver

Caldéraro

Zucman–Rossi

2017

Schiff's Diseases of the Liver

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Hepatocellular Benign Tumors—From Molecular Classification to Personalized Clinical Care

Cited by 255 publications

References 153 publications

Liver transplantation for adenomatosis: European experience

Liver transplantation for adenomatosis: European experience

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

Benign Tumors, Nodules, and Cystic Diseases of the Liver

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