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World Journal of Gastroenterology Apr 2022Hepatocellular adenoma (HCA) is a benign hepatocellular neoplasm, commonly occurs in young women with a history of oral contraceptive use. Complications including...
Hepatocellular adenoma (HCA) is a benign hepatocellular neoplasm, commonly occurs in young women with a history of oral contraceptive use. Complications including hemorrhage and malignant transformation necessitate the need for a thorough understanding of the underlying molecular signatures in this entity. Recent molecular studies have significantly expanded our knowledge of HCAs. The well-developed phenotype-genotype classification system improves clinical management through identifying "high risk" subtype of HCAs. In this article, we attempt to provide updated information on clinical, pathologic and molecular features of each subtype of HCAs.
Topics: Adenoma, Liver Cell; Carcinoma, Hepatocellular; Cell Transformation, Neoplastic; Female; Hemorrhage; Humans; Liver Neoplasms
PubMed: 35582672
DOI: 10.3748/wjg.v28.i14.1384 -
Visceral Medicine Aug 2020Due to the frequent use of medical imaging including ultrasonography, the incidence of benign liver tumors has increased. There is a large variety of different solid... (Review)
Review
BACKGROUND
Due to the frequent use of medical imaging including ultrasonography, the incidence of benign liver tumors has increased. There is a large variety of different solid benign liver tumors, of which hemangioma, focal nodular hyperplasia (FNH), and hepatocellular adenoma (HCA) are the most frequent. Advanced imaging techniques allow precise diagnosis in most of the patients, which reduces the need for biopsies only to limited cases. Patients with benign liver tumors are mostly asymptomatic and do not need any kind of treatment. Symptoms can be abdominal pain and pressure effects on adjacent structures. The 2 most serious complications are bleeding and malignant transformation.
SUMMARY
This review focuses on hepatic hemangioma (HH), FNH, and HCA, and provides an overview on clinical presentations, surgical and interventional treatment, as well as conservative management. Treatment options for HHs, if indicated, include liver resection, radiofrequency ablation, and transarterial catheter embolization, and should be carefully weighed against possible complications. FNH is the most frequent benign liver tumor without any risk of malignant transformation, and treatment should only be restricted to symptomatic patients. HCA is associated with the use of oral contraceptives or other steroid medications. Unlike other benign liver tumors, HCA may be complicated by malignant transformation. HCAs have been divided into 6 subtypes based on molecular and pathological features with different risk of complication.
KEY MESSAGE
The vast majority of benign liver tumors remain asymptomatic, do not increase in size, and rarely need treatment. Biopsies are usually not needed as accurate diagnosis can be obtained using modern imaging techniques.
PubMed: 33005655
DOI: 10.1159/000509145 -
International Journal of Molecular... May 2021Although radiological diagnostics have been progressing, pathological diagnosis remains the most reliable method for diagnosing liver tumors. In some cases, definite... (Review)
Review
Although radiological diagnostics have been progressing, pathological diagnosis remains the most reliable method for diagnosing liver tumors. In some cases, definite pathological diagnosis cannot be obtained by histological evaluation alone, especially when the sample is a small biopsy; in such cases, immunohistochemical staining is very useful. Immunohistochemistry is the most frequently used technique for molecular pathological diagnosis due to its broad application, ease of performance and evaluation, and reasonable cost. The results occasionally reflect specific genetic mutations. The immunohistochemical markers of hepatocellular carcinoma include those of hepatocellular differentiation-such as hepatocyte paraffin 1 and arginase-1-and those of malignant hepatocytes-such as glypican-3, heat shock protein 70, and glutamine synthetase (GS). To classify the subtypes of hepatocellular adenoma, examination of several immunohistochemical markers, such as liver fatty acid-binding protein, GS, and serum amyloid A, is indispensable. Immunohistochemical staining for GS is also important for the diagnosis of focal nodular hyperplasia. The representative immunohistochemical markers of intrahepatic cholangiocarcinoma include cytokeratin (CK) 7 and CK19. In this article, we provide an overview of the application of immunohistochemistry in the pathological diagnosis of liver tumors referring to the association with genetic alterations. Furthermore, we aimed to explain the practical points in the differential diagnosis of liver tumors by immunohistochemical staining.
Topics: Adenoma, Liver Cell; Biomarkers, Tumor; Carcinoma, Hepatocellular; Cholangiocarcinoma; Diagnosis, Differential; Glypicans; Humans; Immunohistochemistry; Keratin-7; Liver Neoplasms
PubMed: 34071338
DOI: 10.3390/ijms22115780 -
Gastroenterology Mar 2017Hepatocellular adenomas (HCAs) are benign liver tumors that can be assigned to molecular subtypes based on inactivating mutations in hepatocyte nuclear factor 1A,...
BACKGROUND & AIMS
Hepatocellular adenomas (HCAs) are benign liver tumors that can be assigned to molecular subtypes based on inactivating mutations in hepatocyte nuclear factor 1A, activating mutations in β-catenin, or activation of inflammatory signaling pathways. We aimed to update the classification system for HCA and associate the subtypes with disease risk factors and complications.
METHODS
We analyzed expression levels of 20 genes and sequenced exon regions of 8 genes (HNF1A, IL6ST, CTNNB1, FRK, STAT3, GNAS, JAK1, and TERT) in 607 samples of 533 HCAs from 411 patients, collected from 28 centers mainly in France from 2000 and 2014. We performed gene expression profile, RNA sequence, whole-exome and genome sequence, and immunohistochemical analyses of select samples. Molecular data were associated with risk factors, histopathology, bleeding, and malignant transformation.
RESULTS
Symptomatic bleeding occurred in 14% of the patients (85% of cases were female, median age, 38 years); 7% of the nodules were borderline between HCA and hepatocellular carcinoma, and 3% of patients developed hepatocellular carcinoma from HCA. Based on molecular features, we classified HCA into 8 subgroups. One new subgroup, composed of previously unclassified HCA, represented 4% of HCAs overall and was associated with obesity and bleeding. These tumors were characterized by activation of sonic hedgehog signaling, due to focal deletions that fuse the promoter of INHBE with GLI1. Analysis of genetic heterogeneity among multiple HCAs, from different patients, revealed a molecular subtype field effect; multiple tumors had different mutations that deregulated similar pathways. Specific molecular subtypes of HCA associated with various HCA risk factors, including imbalances in estrogen or androgen hormones. Specific molecular subgroup of HCA with β-catenin and sonic hedgehog activation associated with malignant transformation and bleeding, respectively.
CONCLUSIONS
Using sequencing and gene expression analyses, we identified a subgroup of HCA characterized by fusion of the INHBE and GLI1 genes and activation of sonic hedgehog pathway. Molecular subtypes of HCAs associated with different patients' risk factors for HCA, disease progression, and pathology features of tumors. This classification system might be used to select treatment strategies for patients with HCA.
Topics: Adenoma; Adolescent; Adult; Aged; Aged, 80 and over; Carcinoma, Hepatocellular; Cell Transformation, Neoplastic; Child; Chromogranins; Cytokine Receptor gp130; Female; GTP-Binding Protein alpha Subunits, Gs; Gene Fusion; Hedgehog Proteins; Hemorrhage; Hepatocyte Nuclear Factor 1-alpha; Humans; Inhibin-beta Subunits; Janus Kinase 2; Liver Neoplasms; Male; Middle Aged; Mutation; Neoplasm Proteins; Protein-Tyrosine Kinases; Risk Factors; STAT3 Transcription Factor; Sequence Analysis, RNA; Signal Transduction; Telomerase; Transcriptome; Young Adult; Zinc Finger Protein GLI1; beta Catenin
PubMed: 27939373
DOI: 10.1053/j.gastro.2016.11.042 -
Journal of Pathology and Translational... May 2021Hepatocellular adenoma (HCA) is a heterogeneous entity, from both the histomorphological and molecular aspects, and the resultant subclassification has brought a strong... (Review)
Review
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.
PubMed: 33823565
DOI: 10.4132/jptm.2021.02.27 -
Molecular Cell Sep 2013The Keap1-Nrf2 system and autophagy are both involved in the oxidative-stress response, metabolic pathways, and innate immunity, and dysregulation of these processes is...
The Keap1-Nrf2 system and autophagy are both involved in the oxidative-stress response, metabolic pathways, and innate immunity, and dysregulation of these processes is associated with pathogenic processes. However, the interplay between these two pathways remains largely unknown. Here, we show that phosphorylation of the autophagy-adaptor protein p62 markedly increases p62's binding affinity for Keap1, an adaptor of the Cul3-ubiquitin E3 ligase complex responsible for degrading Nrf2. Thus, p62 phosphorylation induces expression of cytoprotective Nrf2 targets. p62 is assembled on selective autophagic cargos such as ubiquitinated organelles and subsequently phosphorylated in an mTORC1-dependent manner, implying coupling of the Keap1-Nrf2 system to autophagy. Furthermore, persistent activation of Nrf2 through accumulation of phosphorylated p62 contributes to the growth of human hepatocellular carcinomas (HCCs). These results demonstrate that selective autophagy and the Keap1-Nrf2 pathway are interdependent, and that inhibitors of the interaction between phosphorylated p62 and Keap1 have potential as therapeutic agents against human HCC.
Topics: Adaptor Proteins, Signal Transducing; Adenoma; Amino Acid Sequence; Animals; Autophagy; Carcinoma, Hepatocellular; Crystallography, X-Ray; Cytoskeletal Proteins; Heat-Shock Proteins; Kelch-Like ECH-Associated Protein 1; Liver Neoplasms; Mechanistic Target of Rapamycin Complex 1; Mice; Molecular Sequence Data; Multiprotein Complexes; NF-E2-Related Factor 2; Phosphorylation; Sequestosome-1 Protein; TOR Serine-Threonine Kinases
PubMed: 24011591
DOI: 10.1016/j.molcel.2013.08.003 -
JHEP Reports : Innovation in Hepatology Apr 2022Hepatocellular carcinoma (HCC) is the predominant primary cancer arising from the liver and is one of the major causes of cancer-related mortality worldwide. The... (Review)
Review
Hepatocellular carcinoma (HCC) is the predominant primary cancer arising from the liver and is one of the major causes of cancer-related mortality worldwide. The cellular origin of HCC has been a topic of great interest due to conflicting findings regarding whether it originates in hepatocytes, biliary cells, or facultative stem cells. These cell types all undergo changes during liver injury, and there is controversy about their contribution to regenerative responses in the liver. Most HCCs emerge in the setting of chronic liver injury from viral hepatitis, fatty liver disease, alcohol, and environmental exposures. The injuries are marked by liver parenchymal changes such as hepatocyte regenerative nodules, biliary duct cellular changes, expansion of myofibroblasts that cause fibrosis and cirrhosis, and inflammatory cell infiltration, all of which may contribute to carcinogenesis. Addressing the cellular origin of HCC is the key to identifying the earliest events that trigger it. Herein, we review data on the cells of origin in regenerating liver and HCC and the implications of these findings for prevention and treatment. We also review the origins of childhood liver cancer and other rare cancers of the liver.
PubMed: 35243280
DOI: 10.1016/j.jhepr.2021.100416 -
World Journal of Gastroenterology May 2019Hepatocellular adenoma (HCA) is a rare benign liver tumour associated with the use of oral contraceptives or other steroid medications which occurs predominantly in... (Review)
Review
Hepatocellular adenoma (HCA) is a rare benign liver tumour associated with the use of oral contraceptives or other steroid medications which occurs predominantly in young and middle-aged women. Unlike other benign liver tumours, an HCA may be complicated by bleeding and malignant transformation. HCAs have been divided into four subtypes based on molecular and pathological features: hepatocyte nuclear factor 1α-mutated HCA, inflammatory HCA, β-catenin-mutated HCA, and unclassified HCA. β-catenin-mutated HCA has the highest risk of haemorrhage or malignant transformation. In the latest upgrade of the guidelines regarding the management of benign liver tumours published in 2016 by the European Association for the Study of the Liver, magnetic resonance imaging (MRI) was recognized to be superior to all other imaging modalities in detecting HCAs and in being able to subtype HCAs up to 80%, with positive identification of 1α-mutated HCA or inflammatory HCA achievable with > 90% specificity. This review analyzed the imaging features of HCA using MRI with hepato-specific contrast agents, focusing on the limitations in the HCA characterization.
Topics: Adenoma, Liver Cell; Contrast Media; Diagnosis, Differential; Europe; Female; Gastroenterology; Hepatocyte Nuclear Factor 1-alpha; Humans; Liver; Liver Neoplasms; Magnetic Resonance Imaging; Medical Oncology; Practice Guidelines as Topic; Societies, Medical
PubMed: 31171888
DOI: 10.3748/wjg.v25.i20.2442 -
Liver International : Official Journal... Jul 2020Hepatocellular adenoma (HCA) are benign liver tumours that may be complicated by haemorrhage or malignant transformation to hepatocellular carcinoma. Epidemiological... (Review)
Review
Hepatocellular adenoma (HCA) are benign liver tumours that may be complicated by haemorrhage or malignant transformation to hepatocellular carcinoma. Epidemiological data are fairly outdated, but it is likely to assume that the incidence has increased over the past decades as HCA are more often incidentally found due to the more widespread use of imaging techniques and the increased incidence of obesity. Various molecular subgroups have been described. Each of these molecular subgroups are defined by specific gene mutations and pathway activations. Additionally, they are all related to specific risk factors and show a various biological behaviour. These molecular subgroups may be identified using immunohistochemistry and molecular characterization. Contrast-enhanced MRI is the recommended imaging modality to analyse patients with suspected hepatocellular adenoma allowing to determine the subtype in up to 80%. Surgical resection remains to be the golden standard in treating HCA, although resection is deemed unnecessary in a large number of cases, as studies have shown that the majority of HCA will regress over time without complications such as haemorrhage or malignant transformation occurring. It is preferable to treat patients with suspected HCA in high volume centres with combined expertise of liver surgeons, hepatologists, radiologists and (molecular) pathologists.
Topics: Adenoma, Liver Cell; Carcinoma, Hepatocellular; Humans; Liver Neoplasms; Magnetic Resonance Imaging
PubMed: 32464711
DOI: 10.1111/liv.14547 -
Revista Do Colegio Brasileiro de... 2023hepatocellular adenoma - AHC - is a rare benign neoplasm of the liver more prevalent in women at reproductive age and its main complication is hemorrhage. In the...
INTRODUCTION
hepatocellular adenoma - AHC - is a rare benign neoplasm of the liver more prevalent in women at reproductive age and its main complication is hemorrhage. In the literature, case series addressing this complication are limited.
METHODS
between 2010 and 2022, 12 cases of bleeding AHC were attended in a high-complexity university hospital in southern Brazil, whose medical records were retrospectively evaluated.
RESULTS
all patients were female, with a mean age of 32 years and a BMI of 33kg/m2. The use of oral contraceptives was identified in half of the sample and also half of the patients had a single lesion. The mean diameter of the largest lesion was 9.60cm and the largest lesion was responsible for bleeding in all cases. The presence of hemoperitoneum was documented in 33% of the patients and their age was significantly higher than the patients who did not have hemoperitoneum - 38 vs 30 years, respectively. Surgical resection of the bleeding lesion was performed in 50% of the patients and the median number of days between bleeding and resection was 27 days. In only one case, embolization was used. The relation between ingrowth of the lesions and the time, in months, was not obtained in this study.
CONCLUSION
it is concluded that the bleeding AHC of the present series shows epidemiological agreement with the literature and may suggest that older patients trend to have hemoperitoneum more frequently, a fact that should be investigated in further studies.
Topics: Humans; Female; Adult; Male; Adenoma, Liver Cell; Liver Neoplasms; Carcinoma, Hepatocellular; Hemoperitoneum; Retrospective Studies
PubMed: 37436285
DOI: 10.1590/0100-6991e-20233549-en