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Jain E, Anderson SA, Ollila E, Johnson DB, Chandrashekar DS, Osme A, Goksel B, Lee G, Al Diffalha S, Kakar S, Harada S, Dhall D. Hepatic adenomas in males: Is molecular characterization helpful in guiding its management? Hum Pathol 2025; 159:105795. [PMID: 40379140 DOI: 10.1016/j.humpath.2025.105795] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2025] [Revised: 05/13/2025] [Accepted: 05/13/2025] [Indexed: 05/19/2025]
Abstract
BACKGROUND AND AIMS Hepatocellular adenomas (HCAs) in males are very rare. We performed detailed clinicopathologic, immunohistochemical and molecular characterization of HCAs in males, to understand their pathogenesis and malignant potential. METHODS Seven cases of HCA in males formed our study cohort. The histologic slides, clinical and follow-up information were reviewed and immunohistochemical stains were performed. DNA was extracted and targeted sequencing was performed using Ion Torrent chemistry. Filtered variants were annotated to identify pathogenic mutations. RESULTS Six (86 %) patients were morbidly obese. All showed at least focal cytologic atypia. Three lesions were markedly steatotic and 2 were hemorrhagic. One lesion showed focal reticulin loss, diffuse glutamine synthetase (GS) positivity and beta-catenin (β-catenin) nuclear staining, suggestive of atypical hepatocellular neoplasm. Three (42.8 %) cases were inflammatory-type, showing diffuse serum amyloid-associated protein/C-reactive protein. One other inflammatory-type HCA showed peripheral accentuation with GS and another non-inflammatory HCA showed patchy staining with GS; both revealed CTNBB1 mutations but no β-catenin nuclear staining. None showed TP53, TERT promotor mutations, or significant copy number alterations. CONCLUSION A significant proportion of HCAs in males occurred in obese patients and were inflammatory-type. While some are beta-catenin mutated and need to be resected, a subset of HCAs in males appears to be low-risk by molecular features and may be treated conservatively.
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Affiliation(s)
- Ekta Jain
- Department of Pathology, The University of Alabama at Birmingham, Alabama, USA
| | - Sarah A Anderson
- Department of Pathology, The University of Alabama at Birmingham, Alabama, USA
| | - Eric Ollila
- Department of Pathology, The University of Alabama at Birmingham, Alabama, USA
| | | | | | - Abdullah Osme
- Department of Pathology, The University of Alabama at Birmingham, Alabama, USA
| | - Behiye Goksel
- Department of Pathology, The University of Alabama at Birmingham, Alabama, USA
| | - Goo Lee
- Department of Pathology, The University of Alabama at Birmingham, Alabama, USA
| | - Sameer Al Diffalha
- Department of Pathology, The University of Alabama at Birmingham, Alabama, USA
| | - Sanjay Kakar
- Department of Pathology, University of California, San Francisco, USA
| | - Shuko Harada
- Department of Pathology, The University of Alabama at Birmingham, Alabama, USA.
| | - Deepti Dhall
- Department of Pathology, The University of Alabama at Birmingham, Alabama, USA.
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Heo S, Song IH, Reizine E, Ronot M, Nault JC, Kim HY, Choi SH, Kim SY. Insights into hepatocellular adenomas in Asia: molecular subtypes, clinical characteristics, imaging features, and hepatocellular carcinoma risks. JOURNAL OF LIVER CANCER 2025; 25:67-78. [PMID: 40059521 PMCID: PMC12010821 DOI: 10.17998/jlc.2025.03.06] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/07/2025] [Revised: 03/05/2025] [Accepted: 03/06/2025] [Indexed: 04/11/2025]
Abstract
Hepatocellular adenomas (HCAs) are benign monoclonal liver tumors. Advances in molecular studies have led to the identification of distinct subtypes of HCA with unique pathways, clinical characteristics, and complication risks, underscoring the need for precise diagnosis and tailored management. Malignant transformation and bleeding remain significant concerns. Imaging plays a crucial role in the identification of these subtypes, offering a non-invasive method to guide clinical decision-making. Most studies involving patients with HCAs have been conducted in Western populations; however, the number of studies focused on Asian population has increased in recent years. HCAs exhibit distinct features in Asian population, such as a higher prevalence among male patients and specific subtypes (e.g., inflammatory HCAs). Current clinical guidelines are predominantly influenced by Western data, which may not fully capture these regional differences in epidemiology and subtype distribution. Therefore, this review presents the updated molecular classification of HCAs and their epidemiologic differences between Asian and Western populations, and discuss the role of imaging techniques, particularly magnetic resonance imaging using hepatobiliary contrast agents, in classifying the subtypes and predicting the risk of hepatocellular carcinoma.
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Affiliation(s)
- Subin Heo
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - In Hye Song
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Edouard Reizine
- Service d'Imagerie Médicale, AP-HP, Hôpitaux Universitaires Henri Mondor, Créteil, France
| | - Maxime Ronot
- Service de Radiologie, Hôpital Beaujon, AP-HP, Clichy, France
| | - Jean-Charles Nault
- Service d'hépatologie, Hôpital Avicenne, AP-HP, Bobigny, France
- Université Sorbonne Paris Nord, Bobigny, France
- INSERM UMR 1138, Centre de Recherche des Cordeliers, Université de Paris Cité, Bobigny, France
| | - Hae Young Kim
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Sang Hyun Choi
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - So Yeon Kim
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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3
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Shen L, Altmayer S, Tse JR. Beta-Catenin-Mutated Hepatocellular Adenomas at Hepatobiliary Phase MRI: A Systematic Review and Meta-Analysis. J Magn Reson Imaging 2024; 60:2104-2114. [PMID: 38465878 DOI: 10.1002/jmri.29279] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2023] [Revised: 01/22/2024] [Accepted: 01/23/2024] [Indexed: 03/12/2024] Open
Abstract
BACKGROUND Beta-catenin-mutated hepatocellular adenomas (β-HCAs) can appear iso- to hyperintense at the hepatobiliary phase (HBP) at magnetic resonance imaging (MRI). Given the relatively lower prevalence of β-HCAs, prior studies had limited power to show statistically significant differences in the HBP signal intensity between different subtypes. PURPOSE To assess the diagnostic performance of HBP MRI to discriminate β-HCA from other subtypes. STUDY TYPE Systemic review and meta-analysis. POPULATION Ten original studies were included, yielding 266 patients with 397 HCAs (9%, 36/397 β-HCAs and 91%, 361/397 non-β-HCAs). FIELD STRENGTH/SEQUENCE 1.5 T and 3.0 T, HBP. ASSESSMENT PubMed, Web of Science, and Embase databases were searched from January 1, 2000, to August 31, 2023, for all articles reporting HBP signal intensity in patients with histopathologically proven HCA subtypes. QUADAS-2 was used to assess risk of bias and concerns regarding applicability. STATISTICAL TESTS Univariate random-effects model was used to calculate pooled estimates. Heterogeneity estimates were assessed with I2 heterogeneity index. Meta-regression (mixed-effect model) was used to test for differences in the prevalence of HBP signal between HCA groups. The threshold for statistical significance was set at P < 0.05. RESULTS HBP iso- to hyperintensity was associated with β-HCAs (pooled prevalence was 72.3% in β-HCAs and 6.3% in non-β-HCAs). Pooled sensitivity and specificity were 72.3% (95% confidence interval 54.1-85.3) and 93.7% (93.8-97.7), respectively. Specificity had substantial heterogeneity with I2 of 83% due to one study, but not for sensitivity (I2 = 0). After excluding this study, pooled sensitivity and specificity were 77.4% (59.6-88.8) and 94.1% (88.9-96.9), with no substantial heterogeneity. One study had high risk of bias for patient selection and two studies were rated unclear for two domains. DATA CONCLUSION Iso- to hyperintensity at HBP MRI may help to distinguish β-HCA subtype from other HCAs with high specificity. However, there was heterogeneity in the pooled estimates. LEVEL OF EVIDENCE 3 TECHNICAL EFFICACY: Stage 2.
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Affiliation(s)
- Luyao Shen
- Department of Radiology, Stanford University School of Medicine, Stanford, California, USA
| | - Stephan Altmayer
- Department of Radiology, Stanford University School of Medicine, Stanford, California, USA
| | - Justin R Tse
- Department of Radiology, Stanford University School of Medicine, Stanford, California, USA
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Reguram R, Ghonge A, Tse J, Dhanasekaran R. Practical approach to diagnose and manage benign liver masses. Hepatol Commun 2024; 8:e0560. [PMID: 39470338 PMCID: PMC11524743 DOI: 10.1097/hc9.0000000000000560] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2024] [Accepted: 09/04/2024] [Indexed: 10/30/2024] Open
Abstract
Benign liver lesions are among the most commonly diagnosed abnormalities in liver imaging. They are often discovered incidentally during routine examinations or imaging conducted for unrelated reasons. These can be solid lesions, such as hemangiomas, focal nodular hyperplasia, hepatic adenomas, or cystic lesions. Recent advancements in MRI technology, particularly with hepatocyte-specific contrast agents, have enhanced the characterization of these lesions, reducing the reliance on invasive tissue sampling. Nevertheless, tissue sampling retains a crucial role in the evaluation of indeterminate lesions or those with malignant potential. While most benign liver lesions are asymptomatic, some can become symptomatic, causing discomfort, pain, or bleeding, particularly if the lesion is large. A deep understanding of the molecular underpinnings of the lesions is crucial for tailoring patient management strategies, particularly in distinguishing lesions that require surgical intervention from those that can be monitored. For instance, the molecular subclassification of hepatic adenomas has provided mechanistic insights and identified certain subtypes that are at higher risk of malignancy. Most benign liver lesions can be safely monitored; however, in patients with cirrhosis or a known primary malignancy, a high index of suspicion for cancer is required. It is crucial to carefully evaluate any liver lesion identified in these patients to ensure that indeterminate lesions are not overlooked. Effective management of benign liver lesions involves a multidisciplinary team, including hepatologists, surgeons, and radiologists, ensuring a comprehensive and individualized approach to patient care. This review outlines the clinical presentation of common benign liver lesions, providing a diagnostic and management framework. Emphasis is placed on a personalized approach to minimize patient distress and optimize outcomes by leveraging imaging advancements and multidisciplinary collaboration.
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Affiliation(s)
- Reshma Reguram
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University, Stanford, California, USA
| | - Aishwarya Ghonge
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University, Stanford, California, USA
| | - Justin Tse
- Department of Radiology, Stanford University, Stanford, California, USA
| | - Renumathy Dhanasekaran
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University, Stanford, California, USA
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Choi JH, Thung SN. Pathology and diagnostic approaches to well-differentiated hepatocellular lesions: a narrative review. JOURNAL OF YEUNGNAM MEDICAL SCIENCE 2024; 42:5. [PMID: 39442859 PMCID: PMC11812079 DOI: 10.12701/jyms.2024.00766] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/24/2024] [Revised: 09/09/2024] [Accepted: 09/19/2024] [Indexed: 10/25/2024]
Abstract
Well-differentiated hepatocellular lesions (WDHLs) are liver tumors or nonneoplastic lesions in which the cells closely resemble normal hepatocytes. These lesions often include focal nodular hyperplasia, hepatocellular adenoma, macroregenerative nodule, dysplastic nodule, and well-differentiated hepatocellular carcinoma. The diagnosis of these lesions remains challenging because of their morphological similarities, particularly when examined using needle biopsy. The accurate diagnosis of WDHLs is crucial for patient management and prognosis. This review addresses the histopathological characteristics and diagnostic approaches of WDHLs.
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Affiliation(s)
- Joon Hyuk Choi
- Department of Pathology, Yeungnam University College of Medicine, Daegu, Korea
| | - Swan N. Thung
- Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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6
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Huang Z, Li Y, Chen W, Deng W, Li Y. Insulin-like growth factor-1 deficiency caused by hepatocellular adenoma leads to growth arrest, primary amenorrhea and metabolic syndrome: a case report and 4 years follow up. BMC Endocr Disord 2024; 24:188. [PMID: 39266979 PMCID: PMC11391839 DOI: 10.1186/s12902-024-01716-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2023] [Accepted: 09/03/2024] [Indexed: 09/14/2024] Open
Abstract
BACKGROUND Hepatocellular adenoma (HCA) is a rare benign neoplasm, seldom ascribed as the cause of endocrine and metabolic derangement. We herein report a case of primary amenorrhea, growth arrest and metabolic syndrome. En bloc resection of the tumor normalized all the disturbances. CASE PRESENTATION A 16-year-old girl complained of primary amenorrhea and growth arrest for the past 2 years. Her height and weight were at the 3rd percentile, whereas waist circumference was at the 90th percentile for chronological age. She was hypertensive on admission. Plasma cholesterol, triglyceride and uric acid were elevated. Evaluation of GH/IGF-1 axis showed extremely low IGF-1 concentration, which was unresponsive to hGH stimulation. Computer tomography identified a huge liver mass (18.2 cm×13.7 cm×21 cm). The patient underwent an uneventful open right hepatic lobectomy. The tumor was en bloc resected. Immunohistochemistry indicated an unclassified HCA, which was confirmed by genetic screening. IGF-1 concentration, blood pressure, lipid profile and ovarian function were all normalized after surgery, and the girl had reduction in waist circumference and gain in height during the follow up. CONCLUSION We provide evidence that liver-derived IGF-1 has a direct effect on skeletal and pubertal development, blood pressure, visceral adiposity and dyslipidemia independent of insulin resistance and obesity in the circumstance of undernutrition. Though rare, we propose the need to look into HCA cases for the existence of IGF-1 deficiency and its impact on metabolic derangement.
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Affiliation(s)
- Zhimin Huang
- Department of Endocrinology and Diabetes Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P.R. China.
| | - Yuwen Li
- Department of Hyperbaric Oxygen, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P.R. China
| | - Wenfang Chen
- Department of Pathology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P.R. China
| | - Wanping Deng
- Department of Endocrinology and Diabetes Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P.R. China
| | - Yanbing Li
- Department of Endocrinology and Diabetes Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P.R. China.
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Tóth M, Kirchner M, Longerich T, Stenzinger A, Schirmacher P. Integrated genotype-phenotype analysis of familial adenomatous polyposis-associated hepatocellular adenomas. Virchows Arch 2024; 484:587-595. [PMID: 37872280 PMCID: PMC11062996 DOI: 10.1007/s00428-023-03680-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2023] [Revised: 09/25/2023] [Accepted: 10/10/2023] [Indexed: 10/25/2023]
Abstract
Familial adenomatous polyposis (FAP) is an autosomal dominant syndrome caused by a germline mutation in the adenomatous polyposis coli (APC) gene, characterized by numerous colorectal adenomas. In addition, FAP patients may develop extraintestinal manifestations. Several cases of hepatocellular adenomas (HCA) detected accidentally in FAP patients have raised the so-far unsolved question of whether they represent a specific manifestation of FAP or a mere coincidence. To investigate the incidence of liver tumors in FAP patients, we analyzed our diagnostic database from 1991 to 2021. Among the 58 hepatic mass lesions identified, five HCAs occurring in three patients with FAP were identified, and comprehensive morphological, immunohistological, and molecular analysis employing targeted next-generation sequencing was conducted for characterization. The HCAs in this study showed no cytological or histological atypia. They displayed a diffuse, strong positivity for glutamine synthetase but no nuclear beta-catenin immunostaining. In two patients, the adenomas showed moderate immunoreactivity against serum amyloid A. Consistent with the diagnosis of FAP, molecular profiling revealed a pathogenic germline mutation of the APC gene in all analyzed adenomas as well as deleterious somatic second hits. All somatic mutations were localized between codons 1345 and 1577. No mutations were found in the catenin beta 1 gene. HCA in FAP patients can be a specific, although rare, neoplastic manifestation of this inborn disease and represents a distinct subgroup of HCAs. These benign tumors represent an important differential diagnosis for hepatic metastases in FAP patients and require adequate clinical and molecular (diagnostic) assessments for optimal patient guidance.
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Affiliation(s)
- Marcell Tóth
- Institute of Pathology, University Hospital Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany.
| | - Martina Kirchner
- Institute of Pathology, University Hospital Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany
| | - Thomas Longerich
- Institute of Pathology, University Hospital Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany
| | - Albrecht Stenzinger
- Institute of Pathology, University Hospital Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany
| | - Peter Schirmacher
- Institute of Pathology, University Hospital Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany
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8
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Abdullah AD, Amanpour-Gharaei B, Nassiri Toosi M, Delazar S, Saligheh Rad H, Arian A. Comparing Texture Analysis of Apparent Diffusion Coefficient MRI in Hepatocellular Adenoma and Hepatocellular Carcinoma. Cureus 2024; 16:e51443. [PMID: 38298321 PMCID: PMC10829059 DOI: 10.7759/cureus.51443] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2023] [Accepted: 11/19/2023] [Indexed: 02/02/2024] Open
Abstract
AIM This study aimed to assess the effectiveness of using MRI-apparent diffusion coefficient (ADC) map-driven radiomics to differentiate between hepatocellular adenoma (HCA) and hepatocellular carcinoma (HCC) features. MATERIALS AND METHODS The study involved 55 patients with liver tumors (20 with HCA and 35 with HCC), featuring 106 lesions equally distributed between hepatic carcinoma and hepatic adenoma who underwent texture analysis on ADC map MR images. The analysis identified several imaging features that significantly differed between the HCA and HCC groups. Four classification models were compared for distinguishing HCA from HCC including linear support vector machine (linear-SVM), radial basis function SVM (RBF-SVM), random forest (RF), and k-nearest neighbor (KNN). RESULTS The k-nearest neighbor (KNN) classifier displayed the top accuracy (0.89) and specificity (0.90). Linear-SVM and KNN classifiers showcased the leading sensitivity (0.88) for both, with the KNN classifier achieving the highest precision (0.9). In comparison, the conventional interpretation had lower sensitivity (70.1%) and specificity (77.9%). CONCLUSION The study found that utilizing ADC maps for texture analysis in MR images is a viable method to differentiate HCA from HCC, yielding promising results in identified texture features.
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Affiliation(s)
- Ayoob Dinar Abdullah
- Technology of Radiology and Radiotherapy, Tehran University of Medical Sciences, Tehran, IRN
| | - Behzad Amanpour-Gharaei
- Cancer Biology Research Center, Cancer Institute, Tehran University of Medical Sciences, Tehran, IRN
| | | | - Sina Delazar
- Advanced Diagnostic and Interventional Radiology Research Center, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, IRN
| | - Hamidraza Saligheh Rad
- Medical Physics and Biomedical Engineering, Tehran University of Medical Sciences, Tehran, IRN
| | - Arvin Arian
- Radiology, Cancer Institute, Tehran University of Medical Sciences, Tehran, IRN
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9
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Ferrell LD, Kakar S, Terracciano LM, Wee A. Tumours and Tumour-Like Lesions. MACSWEEN'S PATHOLOGY OF THE LIVER 2024:842-946. [DOI: 10.1016/b978-0-7020-8228-3.00013-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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10
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Chen Y, Wang W, Morgan MP, Robson T, Annett S. Obesity, non-alcoholic fatty liver disease and hepatocellular carcinoma: current status and therapeutic targets. Front Endocrinol (Lausanne) 2023; 14:1148934. [PMID: 37361533 PMCID: PMC10286797 DOI: 10.3389/fendo.2023.1148934] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2023] [Accepted: 05/16/2023] [Indexed: 06/28/2023] Open
Abstract
Obesity is a global epidemic and overwhelming evidence indicates that it is a risk factor for numerous cancers, including hepatocellular carcinoma (HCC), the third leading cause of cancer-related deaths worldwide. Obesity-associated hepatic tumorigenesis develops from nonalcoholic fatty liver disease (NAFLD), progressing to nonalcoholic steatohepatitis (NASH), cirrhosis and ultimately to HCC. The rising incidence of obesity is resulting in an increased prevalence of NAFLD and NASH, and subsequently HCC. Obesity represents an increasingly important underlying etiology of HCC, in particular as the other leading causes of HCC such as hepatitis infection, are declining due to effective treatments and vaccines. In this review, we provide a comprehensive overview of the molecular mechanisms and cellular signaling pathways involved in the pathogenesis of obesity-associated HCC. We summarize the preclinical experimental animal models available to study the features of NAFLD/NASH/HCC, and the non-invasive methods to diagnose NAFLD, NASH and early-stage HCC. Finally, since HCC is an aggressive tumor with a 5-year survival of less than 20%, we will also discuss novel therapeutic targets for obesity-associated HCC and ongoing clinical trials.
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Affiliation(s)
- Yinshuang Chen
- School of Pharmacy and Biomolecular Sciences, Royal College of Surgeons in Ireland, University of Medicine and Health Sciences, Dublin, Ireland
- College of Pharmaceutical Sciences, Soochow University, Suzhou, China
| | - Weipeng Wang
- College of Pharmaceutical Sciences, Soochow University, Suzhou, China
| | - Maria P. Morgan
- School of Pharmacy and Biomolecular Sciences, Royal College of Surgeons in Ireland, University of Medicine and Health Sciences, Dublin, Ireland
| | - Tracy Robson
- School of Pharmacy and Biomolecular Sciences, Royal College of Surgeons in Ireland, University of Medicine and Health Sciences, Dublin, Ireland
| | - Stephanie Annett
- School of Pharmacy and Biomolecular Sciences, Royal College of Surgeons in Ireland, University of Medicine and Health Sciences, Dublin, Ireland
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11
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Heise D, Neumann UP. [Benign solid liver tumors]. CHIRURGIE (HEIDELBERG, GERMANY) 2023:10.1007/s00104-023-01809-w. [PMID: 36811685 DOI: 10.1007/s00104-023-01809-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 01/10/2023] [Indexed: 02/24/2023]
Abstract
Benign solid liver tumors are frequently discovered during routine sonographic examinations. As a rule, malignant tumors can be excluded using contrast medium-based sectional imaging; however, unclear cases can represent a diagnostic challenge. The category of solid benign liver tumors includes first and foremost hepatocellular adenoma (HCA), focal nodular hyperplasia (FNH) and hemangioma. Based on the most recent data, an overview of the current standards in the diagnostics and treatment is given.
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Affiliation(s)
- Daniel Heise
- Klinik für Allgemein‑, Viszeral- und Transplantationschirurgie, Uniklinik Aachen, Pauwelsstr. 30, 52074, Aachen, Deutschland.
| | - Ulf Peter Neumann
- Klinik für Allgemein‑, Viszeral- und Transplantationschirurgie, Uniklinik Aachen, Pauwelsstr. 30, 52074, Aachen, Deutschland
- Department of Surgery, Maastricht University Medical Centre (MUMC), Maastricht, Niederlande
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12
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Wakasa Y, Toyoki Y, Kusumi T, Kameyama Y, Odagiri T, Jin H, Nakai M, Aoki K, Kawashima H, Endo M. β-Catenin-activated inflammatory hepatocellular adenoma with pigmentation and atypical features: a case report. Clin J Gastroenterol 2023; 16:237-243. [PMID: 36640247 DOI: 10.1007/s12328-023-01757-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2022] [Accepted: 01/06/2023] [Indexed: 01/15/2023]
Abstract
Hepatocellular adenomas are rare diseases, defined as benign liver neoplasms composed of cells with hepatocellular differentiation. Differential diagnosis of hepatocellular adenoma from other lesions, including focal nodular hyperplasia and hepatocellular carcinoma, is crucial to determine treatment strategy. We describe a case of β-catenin-activated inflammatory hepatocellular adenoma with malignant transformation. A 50-year-old man with a suspected liver tumor, based on abdominal ultrasonography findings, was referred to our hospital. Contrast-enhanced computed tomography and magnetic resonance imaging revealed a liver tumor in S2 which was enhanced in the arterial phase to the delayed phase. Based on diagnostic imaging findings, hepatocellular adenoma or focal nodular hyperplasia was suspected. We considered the possibility of malignant potential because of the enlargement of the lesion. Thus, we performed a laparoscopic hepatectomy. Histological examination showed pigment deposition in the hepatocytes, which was determined to be lipofuscin. Mild nuclear swelling and atypia in the tumor area indicated nodular growth. Based on the histological and immunohistochemical findings, the diagnosis was ꞵ-catenin-activated inflammatory hepatocellular adenoma with atypical features. The imaging features of hepatocellular adenoma and focal nodular hyperplasia are similar, but if the tumor tends to grow, surgical treatment should be performed because of the possibility of malignant hepatocellular adenoma.
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Affiliation(s)
- Yusuke Wakasa
- Department of General Surgery, Aomori City Hospital, 1-14-20, Katta, Aomori, 030-0821, Japan.
| | - Yoshikazu Toyoki
- Department of General Surgery, Aomori City Hospital, 1-14-20, Katta, Aomori, 030-0821, Japan
| | - Tomomi Kusumi
- Department of Pathology, Aomori City Hospital, Aomori, Japan
| | - Yuma Kameyama
- Department of General Surgery, Aomori City Hospital, 1-14-20, Katta, Aomori, 030-0821, Japan
| | - Tadashi Odagiri
- Department of General Surgery, Aomori City Hospital, 1-14-20, Katta, Aomori, 030-0821, Japan
| | - Hiroyuki Jin
- Department of General Surgery, Aomori City Hospital, 1-14-20, Katta, Aomori, 030-0821, Japan
| | - Makoto Nakai
- Department of General Surgery, Aomori City Hospital, 1-14-20, Katta, Aomori, 030-0821, Japan
| | - Kazunori Aoki
- Department of General Surgery, Aomori City Hospital, 1-14-20, Katta, Aomori, 030-0821, Japan
| | - Hiroaki Kawashima
- Department of General Surgery, Aomori City Hospital, 1-14-20, Katta, Aomori, 030-0821, Japan
| | - Masaaki Endo
- Department of General Surgery, Aomori City Hospital, 1-14-20, Katta, Aomori, 030-0821, Japan
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Shah S, Meka O, Reddy A, Neelam S, Wilcox C. A Rare Presentation of Multiple Hepatic Masses Due to Hepatic Adenoma: A Case Report. J Investig Med High Impact Case Rep 2023; 11:23247096231166676. [PMID: 37056175 PMCID: PMC10116003 DOI: 10.1177/23247096231166676] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2023] [Accepted: 03/12/2023] [Indexed: 04/15/2023] Open
Abstract
Hepatic adenomas (HAs) are rare but benign neoplasms of the liver which predominantly present as solitary lesions in women of reproductive age. The incidence of HAs has increased dramatically since the introduction of oral contraceptive pills (OCPs) along with the rising incidence of obesity. Discontinuation of OCPs and lifestyle modifications, including weight loss regimens, are considered as conservative treatment options for HAs. Large lesions may result in malignant transformation with a higher propensity for hemorrhage. Importantly, larger lesions that do not respond to conservative management require surgical excision. We report a case of a patient presenting with multiple hepatic lesions that were subsequently confirmed as HAs.
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Affiliation(s)
- Shivam Shah
- The University of Alabama System, Tuscaloosa, USA
| | - Omsai Meka
- Wake Forest University School of Medicine, Winston-Salem, NC, USA
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14
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Yang KL, Rogers D. Imaging of Hepatocellular Adenomas: From Molecular Biology to MRI. CURRENT RADIOLOGY REPORTS 2022. [DOI: 10.1007/s40134-022-00400-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
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15
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Shao G, Liu Y, Lu L, Zhang G, Zhou W, Wu T, Wang L, Xu H, Ji G. The Pathogenesis of HCC Driven by NASH and the Preventive and Therapeutic Effects of Natural Products. Front Pharmacol 2022; 13:944088. [PMID: 35873545 PMCID: PMC9301043 DOI: 10.3389/fphar.2022.944088] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2022] [Accepted: 06/20/2022] [Indexed: 12/12/2022] Open
Abstract
Nonalcoholic steatohepatitis (NASH) is a clinical syndrome with pathological changes that are similar to those of alcoholic hepatitis without a history of excessive alcohol consumption. It is a specific form of nonalcoholic fatty liver disease (NAFLD) that is characterized by hepatocyte inflammation based on hepatocellular steatosis. Further exacerbation of NASH can lead to cirrhosis, which may then progress to hepatocellular carcinoma (HCC). There is a lack of specific and effective treatments for NASH and NASH-driven HCC, and the mechanisms of the progression of NASH to HCC are unclear. Therefore, there is a need to understand the pathogenesis and progression of these diseases to identify new therapeutic approaches. Currently, an increasing number of studies are focusing on the utility of natural products in NASH, which is likely to be a promising prospect for NASH. This paper reviews the possible mechanisms of the pathogenesis and progression of NASH and NASH-derived HCC, as well as the potential therapeutic role of natural products in NASH and NASH-derived HCC.
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Affiliation(s)
- Gaoxuan Shao
- Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Ying Liu
- Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Lu Lu
- Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Guangtao Zhang
- Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Wenjun Zhou
- Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Tao Wu
- Institute of Interdisciplinary Integrative Biomedical Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Lei Wang
- Department of Hepatology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Hanchen Xu
- Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Guang Ji
- Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
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16
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Focal Benign Liver Lesions and Their Diagnostic Pitfalls. Radiol Clin North Am 2022; 60:755-773. [DOI: 10.1016/j.rcl.2022.05.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
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17
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Digestive Health in Sexual and Gender Minority Populations. Am J Gastroenterol 2022; 117:865-875. [PMID: 35537864 DOI: 10.14309/ajg.0000000000001804] [Citation(s) in RCA: 32] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2022] [Accepted: 04/22/2022] [Indexed: 12/11/2022]
Abstract
It has been over 50 years since the Stonewall Inn Riots in June 1969, a seminal event for the lesbian, gay, bisexual, transgender, queer, intersex, and other sexual and gender-diverse minorities (LGBTQI+, or lesbian, gay, bisexual, transgender, queer, intersex, and everyone else) rights movement. However, sexual and gender minority (SGM) individuals still face discrimination and harassment due to their sexual orientation or gender identity. As such, the National Institute on Minority Health and Health Disparities has identified SGM communities as a "health disparity population." Broadly, there are higher rates of sexually transmitted infections, substance use and abuse, mental health conditions, obesity and eating disorders, certain cancers (breast, cervical, and anorectal), and cardiovascular disease in SGM communities. Transgender patients, especially those of color, are more likely to be uninsured, experience discrimination, and be denied health care than cisgender patients. In addition, SGM individuals have twice the risk of lifetime exposure to emotional, physical, and sexual trauma compared with heterosexuals. It is expected all these factors would negatively affect digestive health as well. This review summarizes the effects of social determinants of health and discrimination on health care access, highlights important digestive diseases to consider in the SGM population, and offers solutions to improve and prioritize the health of these communities. We aim to draw attention to SGM-specific issues that affect gastrointestinal health and spur research that is desperately lacking.
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18
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Oudmaijer CAJ, Berk KA, van der Louw EJTM, de Man R, van der Lelij AJ, Hoeijmakers JHJ, IJzermans J. KETOgenic diet therapy in patients with HEPatocellular adenoma: study protocol of a matched interventional cohort study. BMJ Open 2022; 12:e053559. [PMID: 35168973 PMCID: PMC8852750 DOI: 10.1136/bmjopen-2021-053559] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
INTRODUCTION Hepatocellular adenoma (HCA) is an uncommon, solid and benign liver lesion, mainly occurring in women using oral contraceptives. Patients are advised to stop using oral contraceptives (OC) and, as overweight is frequently observed, dietary restrictions. Metabolic changes are assumed to play a role and it has been suggested that diet may help to reduce tumour size. A low-calorie ketogenic diet (LCKD) has been shown to induce weight loss and multiple metabolic changes, including the reduction of portal insulin concentrations, which downregulates hepatic growth hormone receptors. Weight reduction and an LCKD can potentially reduce the size of HCAs. METHODS AND ANALYSIS We designed a matched, interventional cohort study to determine the effect of an LCKD on the regression of HCA. The study population consists of female subjects with an HCA, 18-50 years of age, body mass index>25 kg/m2, who are entering a surveillance period including cessation of OC. A historical control group will be matched. The intervention consists of an LCKD (approximately 35 g carbohydrate/1500 kcal/day) for 3 months, followed by a less strict LCKD for 3 months (approximately 60 g carbohydrate/1500 kcal/day). Main study endpoint is the diameter of the HCA after 6 months, as compared with the historic control group. Secondary endpoints include adherence, quality of life, change in physical activity, liver fat content, body weight, body composition and resting energy expenditure. ETHICS AND DISSEMINATION The medical ethical committee has approved the study protocol, patient information files and consent procedure and other study-related documents and procedures. TRIAL REGISTRATION NUMBER NL75014.078.20; Pre-results. https://www.trialregister.nl/trial/9092.
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Affiliation(s)
- Christiaan Albert Johan Oudmaijer
- Erasmus MC Transplant Institute, Department of Surgery, Division of Hepatobiliary and Transplantation Surgery, Erasmus MC, Rotterdam, Zuid-Holland, The Netherlands
- Princess Maxima Center for Pediatric Oncology, Utrecht, The Netherlands
| | - Kirsten Anna Berk
- Department of Internal Medicine, Division of Dietetics, Erasmus MC, Rotterdam, Zuid-Holland, The Netherlands
| | | | - Rob de Man
- Department of Hepato-Gastroenterology, Erasmus MC, Rotterdam, Zuid-Holland, The Netherlands
| | - Aart-Jan van der Lelij
- Department of Internal Medicine, Division of Endocrinology, Erasmus MC, Rotterdam, Zuid-Holland, The Netherlands
| | - Jan Hendrik Jozef Hoeijmakers
- Princess Maxima Center for Pediatric Oncology, Utrecht, The Netherlands
- Erasmus MC Cancer Institute, Department of Molecular Genetics, Erasmus MC, Rotterdam, Zuid-Holland, The Netherlands
| | - Jan IJzermans
- Erasmus MC Transplant Institute, Department of Surgery, Division of Hepatobiliary and Transplantation Surgery, Erasmus MC, Rotterdam, Zuid-Holland, The Netherlands
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19
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Verde F, Ponsiglione A. Role of perfusion features in contrast-enhanced ultrasound differential diagnosis of hepatocellular adenoma and carcinoma: Far beyond the gray-scale ultrasound. JOURNAL OF CLINICAL ULTRASOUND : JCU 2022; 50:222-223. [PMID: 35147999 DOI: 10.1002/jcu.23140] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/30/2021] [Accepted: 12/30/2021] [Indexed: 06/14/2023]
Affiliation(s)
- Francesco Verde
- Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy
| | - Andrea Ponsiglione
- Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy
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20
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McDermott C, Ertreo M, Jha R, Ko J, Fernandez S, Desale S, Fishbein T, Satoskar R, Winslow E, Smith C, Hsu CC. Risk factors for bleeding hepatocellular adenoma in a United States cohort. Liver Int 2022; 42:224-232. [PMID: 34687281 DOI: 10.1111/liv.15087] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2021] [Revised: 09/20/2021] [Accepted: 10/07/2021] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS Known risk factors for hepatocellular adenoma (HCA) bleeding are size >5 cm, growth rate, visible vascularity, exophytic lesions, β-catenin and Sonic Hedgehog activated HCAs. Most studies are based on European cohorts. The objective of this study is to identify additional risk factors for HCA bleeding in a US cohort. METHODS Retrospective chart review was performed on patients diagnosed with HCA on magnetic resonance imaging (n = 184) at an academic tertiary institution. Clinical, pathological, and imaging data were collected. Primary outcomes measured were HCA bleeding and malignancy. Statistical analysis was performed with SAS 9.4 using Chi-Square, Fisher's exact test, sample t test, non-parametric Wilcoxon test, and logistic regression. RESULTS After excluding patients whose pathology showed focal nodular hyperplasia and non-adenoma lesions, follow-up data were available for 167 patients. 16% experienced microscopic or macroscopic bleeding and 1.2% had malignancy. HCA size predicted bleeding (P < .0001) and no patients with lesion size <1.8 cm bled. In unadjusted analysis, hepatic adenomatosis (≥10 lesions) trended towards 2.8-fold increased risk of bleeding. Of patients with a single lesion that bled, 77% bled from a lesion >5 cm. In patients with multiple HCAs that bled, 50% bled from lesions <5 cm. In patients with multiple adenomas, size (P = .001) independently predicted bleeding and hepatic steatosis trended towards increased risk of bleeding (P = .05). CONCLUSIONS In a large US cohort, size predicted increased risk of HCA bleeding while hepatic adenomatosis trended towards increased risk of bleeding. In patients with multiple HCAs, size predicted bleeding and hepatic steatosis trended toward increased risk of bleeding.
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Affiliation(s)
- Chelsea McDermott
- Department of Surgery, MedStar Georgetown University Hospital, Washington, District of Columbia, USA
| | - Marco Ertreo
- Department of Radiology, MedStar Georgetown University Hospital, Washington, District of Columbia, USA
| | - Reena Jha
- Department of Radiology, MedStar Georgetown University Hospital, Washington, District of Columbia, USA
| | - Jimin Ko
- Department of Surgery, MedStar Georgetown University Hospital, Washington, District of Columbia, USA
| | | | - Sameer Desale
- MedStar Health Research Institute, Hyattsville, Maryland, USA
| | - Thomas Fishbein
- Department of Surgery, MedStar Georgetown University Hospital, Washington, District of Columbia, USA.,MedStar Georgetown Transplant Institute, MedStar Georgetown University Hospital, Washington, District of Columbia, USA
| | - Rohit Satoskar
- Department of Surgery, MedStar Georgetown University Hospital, Washington, District of Columbia, USA.,MedStar Georgetown Transplant Institute, MedStar Georgetown University Hospital, Washington, District of Columbia, USA
| | - Emily Winslow
- Department of Surgery, MedStar Georgetown University Hospital, Washington, District of Columbia, USA.,MedStar Georgetown Transplant Institute, MedStar Georgetown University Hospital, Washington, District of Columbia, USA
| | - Coleman Smith
- MedStar Georgetown Transplant Institute, MedStar Georgetown University Hospital, Washington, District of Columbia, USA.,Department of Medicine, Medstar Georgetown University Hospital, Washington, District of Columbia, USA
| | - Christine C Hsu
- MedStar Georgetown Transplant Institute, MedStar Georgetown University Hospital, Washington, District of Columbia, USA.,Department of Medicine, Medstar Georgetown University Hospital, Washington, District of Columbia, USA
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21
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Acher AW, Rahnemai-Azar AA, Weber SM, Pawlik TM. Surgical Approach to Pancreas, Liver, Biliary Physiologic Impairment. THE IASGO TEXTBOOK OF MULTI-DISCIPLINARY MANAGEMENT OF HEPATO-PANCREATO-BILIARY DISEASES 2022:31-49. [DOI: 10.1007/978-981-19-0063-1_5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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22
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van Rosmalen BV, Furumaya A, Klompenhouwer AJ, Tushuizen ME, Braat AE, Reinten RJ, Ligthart MAP, Haring MPD, de Meijer VE, van Voorthuizen T, Takkenberg RB, Dejong CHC, de Man RA, IJzermans JNM, Doukas M, van Gulik TM, Verheij J, the Dutch Benign Liver Tumor Group and the PALGA group. Hepatocellular adenoma in men: A nationwide assessment of pathology and correlation with clinical course. Liver Int 2021; 41:2474-2484. [PMID: 34155783 PMCID: PMC8518832 DOI: 10.1111/liv.14989] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/09/2021] [Revised: 05/27/2021] [Accepted: 06/05/2021] [Indexed: 12/15/2022]
Abstract
BACKGROUND & AIMS Hepatocellular adenomas (HCA) rarely occur in males, and if so, are frequently associated with malignant transformation. Guidelines are based on small numbers of patients and advise resection of HCA in male patients, irrespective of size or subtype. This nationwide retrospective cohort study is the largest series of HCA in men correlating (immuno)histopathological and molecular findings with the clinical course. METHODS Dutch male patients with available histological slides with a (differential) diagnosis of HCA between 2000 and 2017 were identified through the Dutch Pathology Registry (PALGA). Histopathology and immunohistochemistry according to international guidelines were revised by two expert hepatopathologists. Next generation sequencing (NGS) was performed to confirm hepatocellular carcinoma (HCC) and/or subtype HCA. Final pathological diagnosis was correlated with recurrence, metastasis and death. RESULTS A total of 66 patients from 26 centres fulfilling the inclusion criteria with a mean (±SD) age of 45.0 ± 21.6 years were included. The diagnosis was changed after expert revision and NGS in 33 of the 66 patients (50%). After a median follow-up of 9.6 years, tumour-related mortality of patients with accessible clinical data was 1/18 (5.6%) in HCA, 5/14 (35.7%) in uncertain HCA/HCC and 4/9 (44.4%) in the HCC groups (P = .031). Four B-catenin mutated HCA were identified using NGS, which were not yet identified by immunohistochemistry and expert revision. CONCLUSIONS Expert revision with relevant immunohistochemistry may help the challenging but prognostically relevant distinction between HCA and well-differentiated HCC in male patients. NGS may be more important to subtype HCA than indicated in present guidelines.
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Affiliation(s)
- Belle V. van Rosmalen
- Department of SurgeryCancer Center AmsterdamAmsterdam UMCUniversity of AmsterdamAmsterdamthe Netherlands
| | - Alicia Furumaya
- Department of SurgeryCancer Center AmsterdamAmsterdam UMCUniversity of AmsterdamAmsterdamthe Netherlands
| | - Anne J. Klompenhouwer
- Department of Gastroenterology and HepatologyErasmus MCUniversity Medical Center RotterdamRotterdamthe Netherlands
| | - Maarten E. Tushuizen
- Department of Gastroenterology and HepatologyLUMCLeiden UniversityLeidenthe Netherlands
| | | | - Roy J. Reinten
- Department of PathologyCancer Center AmsterdamAmsterdam UMCUniversity of AmsterdamAmsterdamthe Netherlands
| | - Marjolein A. P. Ligthart
- Department of Surgery and School of Nutrition and Translational Research in MetabolismMaastricht University Medical CenterMaastrichtthe Netherlands
| | - Martijn P. D. Haring
- Department of SurgeryUniversity Medical Center GroningenUniversity of GroningenGroningenthe Netherlands
| | - Vincent E. de Meijer
- Department of SurgeryUniversity Medical Center GroningenUniversity of GroningenGroningenthe Netherlands
| | | | - R. Bart Takkenberg
- Department of Gastroenterology and HepatologyCancer Center AmsterdamAmsterdam UMCUniversity of AmsterdamAmsterdamthe Netherlands
| | - Cornelis H. C. Dejong
- Department of Surgery and School of Nutrition and Translational Research in MetabolismMaastricht University Medical CenterMaastrichtthe Netherlands,Department of SurgeryUniversitätsklinikum AachenAachenGermany
| | - Robert A. de Man
- Department of Gastroenterology and HepatologyErasmus MCUniversity Medical Center RotterdamRotterdamthe Netherlands
| | - Jan N. M. IJzermans
- Department of SurgeryErasmus MCUniversity Medical Center RotterdamRotterdamthe Netherlands
| | - Michail Doukas
- Department of PathologyErasmus MCUniversity Medical Center RotterdamRotterdamthe Netherlands
| | - Thomas M. van Gulik
- Department of SurgeryCancer Center AmsterdamAmsterdam UMCUniversity of AmsterdamAmsterdamthe Netherlands
| | - Joanne Verheij
- Department of PathologyCancer Center AmsterdamAmsterdam UMCUniversity of AmsterdamAmsterdamthe Netherlands
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Ostojic A, Mrzljak A, Mikulic D. Liver transplantation for benign liver tumors. World J Hepatol 2021; 13:1098-1106. [PMID: 34630877 PMCID: PMC8473500 DOI: 10.4254/wjh.v13.i9.1098] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2021] [Revised: 05/12/2021] [Accepted: 07/21/2021] [Indexed: 02/06/2023] Open
Abstract
Benign liver tumors are common lesions that are usually asymptomatic and are often found incidentally due to recent advances in imaging techniques and their widespread use. Although most of these tumors can be managed conservatively or treated by surgical resection, liver transplantation (LT) is the only treatment option in selected patients. LT is usually indicated in patients that present with life-threatening complications, when the lesions are diffuse in the hepatic parenchyma or when malignant transformation cannot be ruled out. However, due to the significant postoperative morbidity of the procedure, scarcity of available donor liver grafts, and the benign course of the disease, the indications for LT are still not standardized. Hepatic adenoma and adenomatosis, hepatic hemangioma, and hepatic epithelioid hemangioendothelioma are among the most common benign liver tumors treated by LT. This article reviews the role of LT in patients with benign liver tumors. The indications for LT and long-term outcomes of LT are presented.
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Affiliation(s)
- Ana Ostojic
- Department of Gastroenterology and Hepatology, University Hospital Center Zagreb, Zagreb 10000, Croatia
| | - Anna Mrzljak
- Department of Gastroenterology and Hepatology, University Hospital Center Zagreb, Zagreb 10000, Croatia
| | - Danko Mikulic
- Department of Surgery, University Hospital Merkur, Zagreb 10000, Croatia.
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24
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Brunt EM, Sempoux C, Bioulac-Sage P. Hepatocellular adenomas: the expanding epidemiology. Histopathology 2021; 79:20-22. [PMID: 34115403 DOI: 10.1111/his.14343] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/24/2021] [Indexed: 12/16/2022]
Affiliation(s)
- Elizabeth M Brunt
- Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO, USA
| | - Christine Sempoux
- Service of Clinical Pathology, Institute of Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
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25
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Chandler CM, Labadie KP, Park JO, Truong CD. Hepatocellular carcinoma arising within a β-catenin mutated inflammatory hepatic adenoma. HUMAN PATHOLOGY: CASE REPORTS 2021. [DOI: 10.1016/j.ehpc.2021.200501] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022] Open
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26
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Silva TS, Sung M, Nelson DW, DiFronzo AL, O'Connor VV. A Multicenter, 10-Year Experience With Hepatocellular Adenoma: Risk Factors and Disease Course. Am Surg 2021; 88:2345-2350. [PMID: 33861649 DOI: 10.1177/00031348211011084] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Abstract
BACKGROUND Management of hepatocellular adenoma (HA) is marked by a paucity of recent studies. Long-term follow-up data from an equal access health care system may facilitate our understanding of the natural disease course of HA and identify modifiable risk factors. METHODS A multi-institutional, retrospective review of patients with HA from 2008-2017 was performed. Patient demographics, disease characteristics, and clinical outcomes were analyzed. RESULTS Of 124 patients identified, 94% were women with a mean age at diagnosis of 39.5 years (range 20-82). Median follow-up was 22.5 months (range 0-114) with thirty-four (27.4%) patients eventually undergoing hepatectomy. Mean BMI of the study population was 30.5 kg/m2 (range 16-72). Stratified by size, average BMI for adenomas ≥5 cm was 34 kg/m2 compared to 28 kg/m2 for those <5 cm (P < .05). The predominant symptom at presentation was abdominal pain (41.1%), while just 4% presented with acute rupture. Overall incidence of the malignancy was 2.5%. Among all patients, oral contraceptive use was documented in 74 (59.7%) patients, of whom 36 (29.0%) discontinued OC for at least six months. Regression after OC cessation occurred in seven patients (19.4%) while the majority (77.8%) remained stable. DISCUSSION This decade-long review analyzing the impact of modifiable risk factors identifies a direct correlation between BMI and hepatocellular adenoma size. Rupture and malignant transformation are rare entities. Cessation of OC appears to be an effective strategy in the management of hepatic adenoma. Further investigations are warranted to determine if addressing modifiable risk factors such as BMI might induce further HA regression.
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Affiliation(s)
- Trevor S Silva
- Department of Surgery, 472028Riverside University Health System, Moreno Valley, CA, USA
| | - Michael Sung
- Department of Surgery, Kaiser Permanente Los Angeles Medical Center, Los Angeles, CA, USA
| | - Daniel W Nelson
- Department of Surgery, 19925William Beaumont Army Medical Center, El Paso, TX, USA
| | - Andrew L DiFronzo
- Department of Surgery, Kaiser Permanente Los Angeles Medical Center, Los Angeles, CA, USA
| | - Victoria V O'Connor
- Department of Surgery, Kaiser Permanente Los Angeles Medical Center, Los Angeles, CA, USA
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27
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Deniz K, Umetsu SE, Ferrell L, Yılmaz F, Güllüoğlu M, Sağol Ö, Doğusoy GB, Kırımlıoğlu H, Turhan N, Doran F, Kepil N, Çelikel ÇA, Nart D, Özgüven BY, Ceyran B, Karadağ N, Kır G, Erden E, Yılmaz G, Akyol G. Hepatocellular adenomas in the Turkish population: reclassification according to updated World Health Organization criteria. Histopathology 2021; 79:23-33. [PMID: 33406290 DOI: 10.1111/his.14330] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2020] [Revised: 12/31/2020] [Accepted: 01/06/2021] [Indexed: 11/30/2022]
Abstract
AIMS Hepatocellular adenoma (HCA) is an uncommon liver neoplasm, and studies of HCA subtypes have been primarily limited to France, the USA, and Japan. The aim of this study was to describe the clinicopathological features of HCA subtypes in Turkey. METHODS AND RESULTS The resection specimens of 59 cases diagnosed as 'hepatocellular adenoma' collected from 15 institutions were reviewed to confirm the diagnosis and to classify them according to the current World Health Organization 2019 classification. Immunostaining for glutamine synthetase, liver fatty acid-binding protein, C-reactive protein, β-catenin and reticulin was performed. Of the 59 cases, 48 (81%) were diagnosed as HCA. We identified 24 (50%) hepatocyte nuclear factor 1α (HNF1α)-inactivated HCAs, five (10%) inflammatory HCAs, 15 (32%) β-catenin-activated HCAs, three (6%) β-catenin-activated inflammatory HCAs, and one (2%) unclassified HCA. HCA patients were predominantly female (female/male ratio of 5:1); they had a median age of 34 years and a median tumour diameter of 60 mm. In the β-catenin-activated HCA group, nine cases (19%) showed cytoarchitectural atypia, and were also referred to as atypical hepatocellular neoplasms. In the β-catenin-activated HCA group, three cases (6%) showed focal areas supportive of transition to HCA. The original diagnosis of HCA was changed to well-differentiated hepatocellular carcinoma in nine cases and to focal nodular hyperplasia in two cases. CONCLUSION In our series, the major HCA subtype was HNF1α-inactivated HCA. We found a low incidence of inflammatory-type HCA. Our data also showed that β-catenin-activated hepatocellular neoplasms, including cases with atypical histology, constituted a relatively high proportion of the cases. These findings are in contrast to those of most other studies of HCA subtypes.
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Affiliation(s)
- Kemal Deniz
- Department of Pathology, Erciyes University, Kayseri, Turkey
| | - Sarah E Umetsu
- Department of Pathology, University of California San Francisco, San Francisco, CA, USA
| | - Linda Ferrell
- Department of Pathology, University of California San Francisco, San Francisco, CA, USA
| | - Funda Yılmaz
- Department of Pathology, Ege University, İzmir, Turkey
| | - Mine Güllüoğlu
- Department of Pathology, İstanbul University, İstanbul, Turkey
| | - Özgül Sağol
- Department of Pathology, Dokuz Eylül University, İzmir, Turkey
| | - Gülen B Doğusoy
- Department of Pathology, Florence Nightingale University, İstanbul, Turkey
| | | | - Nesrin Turhan
- Department of Pathology, Ankara City Hospital, Ankara, Turkey
| | - Figen Doran
- Department of Pathology, Çukurova University, Adana, Turkey
| | - Nuray Kepil
- Department of Pathology, Cerrahpaşa University, İstanbul, Turkey
| | | | - Deniz Nart
- Department of Pathology, Ege University, İzmir, Turkey
| | - Banu Y Özgüven
- Department of Pathology, Şişli Hamidiye Etfal Research and Training Hospital, İstanbul, Turkey
| | - Bahar Ceyran
- Department of Pathology, Demiroğlu Bilim University, İstanbul, Turkey
| | - Neşe Karadağ
- Department of Pathology, İnönü University, Malatya, Turkey
| | - Gözde Kır
- Department of Pathology, Medeniyet University, İstanbul, Turkey
| | - Esra Erden
- Department of Pathology, Ankara University, Ankara, Turkey
| | - Güldal Yılmaz
- Department of Pathology, Gazi University, Ankara, Turkey
| | - Gülen Akyol
- Department of Pathology, Gazi University, Ankara, Turkey
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Kim SM, Hwang S, Ahn CS, Kim KH, Moon DB, Ha TY, Song GW, Jung DH, Park GC, Hong SM. Clinicopathological features and post-resection outcomes of hepatocellular adenoma. Ann Hepatobiliary Pancreat Surg 2021; 25:25-33. [PMID: 33649251 PMCID: PMC7952660 DOI: 10.14701/ahbps.2021.25.1.25] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2020] [Revised: 09/29/2020] [Accepted: 10/01/2020] [Indexed: 11/28/2022] Open
Abstract
Backgrounds/Aims Hepatocellular adenomas (HCA) are rare benign liver tumors with the potential of malignant transformation and risk of bleeding. We investigated the clinicopathological features and outcomes of HCA in 19 patients who underwent surgical resection. Methods This retrospective observational study included 19 patients who underwent hepatic resection during a 9-year period from 2011 to 2019. Results The incidence of HCA was 0.18% of all hepatic resection cases during the study period. The mean age of the patients was 34.3±9.6 years, and 12 patients (63.2%) were female. Abdominal pain was present as initial clinical manifestation in 5 patients and the other 14 patients had no specific symptoms. HCA was diagnosed in 7 out of 8 patients who underwent liver biopsy. R0 resection was performed in 18 patients (94.7%) and laparoscopic liver resection was performed in 11 patients (57.9%). The mean tumor size was 5.6±3.6 cm and 17 patients had a single tumor. Immunohistochemical analysis of the resected tumor specimens revealed hepatocyte-nuclear-factor-1α mutated HCA in 2 (10.5%), β-catenin-mutated HCA in 2 (10.5%), inflammatory HCA in 12 (63.2%) and unclassified HCA in 3 (15.8%). There were no pathognomonic findings in the preoperative liver imaging studies among these four groups. Currently, all patients are alive with a mean follow-up period of 40.1±26.3 months. One patient showed residual tumors after incomplete resection. Conclusions Surgical resection may be indicated if imaging studies show diagnostic ambiguity, growing tumor or symptomatic mass. Because of the risk of tumor recurrence and malignant transformation, long-term follow-up is necessary.
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Affiliation(s)
- Sung-Min Kim
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Shin Hwang
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Chul-Soo Ahn
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Ki-Hun Kim
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Deok-Bog Moon
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Tae-Yong Ha
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Gi-Won Song
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Dong-Hwan Jung
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Gil-Chun Park
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Seung-Mo Hong
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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Mittal S, Gopal P, Khatri G, Singal AG. Evaluation and Management of Hepatocellular Adenomas. Clin Liver Dis (Hoboken) 2021; 17:57-60. [PMID: 33680436 PMCID: PMC7916436 DOI: 10.1002/cld.949] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2019] [Revised: 12/29/2019] [Accepted: 02/05/2020] [Indexed: 02/04/2023] Open
Affiliation(s)
- Sukul Mittal
- Division of Digestive and Liver DiseasesUT Southwestern Medical CenterDallasTX
- Department of PathologyUT Southwestern Medical CenterDallasTX
- Department of RadiologyUT Southwestern Medical CenterDallasTX
| | - Purva Gopal
- Division of Digestive and Liver DiseasesUT Southwestern Medical CenterDallasTX
- Department of PathologyUT Southwestern Medical CenterDallasTX
- Department of RadiologyUT Southwestern Medical CenterDallasTX
| | - Gaurav Khatri
- Division of Digestive and Liver DiseasesUT Southwestern Medical CenterDallasTX
- Department of PathologyUT Southwestern Medical CenterDallasTX
- Department of RadiologyUT Southwestern Medical CenterDallasTX
| | - Amit G. Singal
- Division of Digestive and Liver DiseasesUT Southwestern Medical CenterDallasTX
- Department of PathologyUT Southwestern Medical CenterDallasTX
- Department of RadiologyUT Southwestern Medical CenterDallasTX
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Yoon PD, Chen AZL, Tovmassian D, Pleass H. Spontaneous hepatic haemorrhage secondary to ruptured hepatocellular adenoma in a young male patient. BMJ Case Rep 2020; 13:13/8/e235966. [PMID: 32843462 DOI: 10.1136/bcr-2020-235966] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023] Open
Abstract
A 27-year-old man presented with acute right upper quadrant abdominal pain and vomiting. He was clinically in hypovolaemic shock. Investigations revealed normocytic anaemia with a normal bilirubin and moderate liver function test abnormalities. CT abdomen and pelvis demonstrated haemoperitoneum and a large solitary hepatic mass in segments V and VI, suspicious for a ruptured hepatic tumour. Massive transfusion protocol was commenced and angioembolisation of the inferior branch of the right hepatic artery was undertaken. Despite this, his haemorrhagic shock was resistant to resuscitation. Thus, he underwent emergent exploratory laparotomy, which resulted in segments V and VI liver resection and packing. Re-look laparotomy 2 days following initial exploration was performed where haemostasis was confirmed. Histopathology revealed a ruptured well-differentiated hepatocellular adenoma. The patient made a good recovery following a 2-week admission.
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Affiliation(s)
- Peter Daechul Yoon
- Department of Surgery, Westmead Hospital, Westmead, New South Wales, Australia
| | - Andy Ze Lin Chen
- Department of Surgery, Westmead Hospital, Westmead, New South Wales, Australia
| | - David Tovmassian
- Department of Surgery, Westmead Hospital, Westmead, New South Wales, Australia
| | - Henry Pleass
- Department of Surgery, Westmead Hospital, Westmead, New South Wales, Australia.,Westmead Clinical School, The University of Sydney, Sydney, New South Wales, Australia
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31
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Goonawardena J, Ratnayake C, Cheung KT, Fox A. Should bariatric surgery be offered for hepatocellular adenomas in obese patients? Surg Obes Relat Dis 2020; 16:2117-2124. [PMID: 32771427 DOI: 10.1016/j.soard.2020.06.043] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2020] [Revised: 06/04/2020] [Accepted: 06/23/2020] [Indexed: 11/19/2022]
Abstract
BACKGROUND Obesity and metabolic syndrome are increasingly recognized as risk factors for development of hepatocellular adenoma (HCA). The implications of weight loss on HCA regression has not been previously reviewed. OBJECTIVES To analyze the effects of surgical and nonsurgical weight loss on HCA. SETTING University Tertiary Hospital. METHODS Literature review of full-text articles from PubMed and Scopus on patients with HCA who underwent surgical or nonsurgical weight loss was performed. Only English language articles were included and editorial comments were excluded. Wilcoxon signed rank test was used for paired data analysis. Spearman correlation was used for correlation between percent excess weight loss (%EWL) and number and size of HCA lesions. RESULTS Out of 4 studies, 7 patients were included in this review, all of whom were female. The median preintervention body mass index was 41 kg/m2 compared with the postintervention body mass index of 28 kg/m2 (P = .002). The %EWL following intervention positively correlated to reduction in number of HCA lesions (%) postintervention, with a Spearman correlation of .78 (P = .04). Similarly, %EWL postintervention was positively correlated, though not statistically significant, to reduction in lesion size (%), with a Spearman correlation of .46 (P = .29). All patients who were candidates for liver resection preintervention based on lesion size > 5 cm avoided liver resection postintervention following surgical and nonsurgical weight loss. CONCLUSIONS Effective long-term weight loss by surgical and nonsurgical methods result in regression of HCAs. Weight loss could avoid major liver resections or decrease the morbidity associated with liver surgery. Bariatric surgery should be considered as an option for management of surgically challenging HCAs in carefully selected obese patients. Multicenter long-term trials, while adjusting for cofounding factors, are required to determine the effects of surgical compared with nonsurgical weight loss on maintenance of HCA regression.
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Affiliation(s)
| | - Chathri Ratnayake
- Department of Internal Medicine, Eastern Health, Box Hill, Victoria, Australia
| | - King Tung Cheung
- Department of Internal Medicine, Eastern Health, Box Hill, Victoria, Australia
| | - Adrian Fox
- Hepatobiliary Unit, Department of General Surgery, Eastern Health, Box Hill, Victoria, Australia; Monash University Eastern Health Clinical School, Box Hill, Victoria, Australia
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Klompenhouwer AJ, de Man RA, Dioguardi Burgio M, Vilgrain V, Zucman‐Rossi J, Ijzermans JNM. New insights in the management of Hepatocellular Adenoma. Liver Int 2020; 40:1529-1537. [PMID: 32464711 PMCID: PMC7383747 DOI: 10.1111/liv.14547] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2020] [Revised: 04/30/2020] [Accepted: 05/21/2020] [Indexed: 12/12/2022]
Abstract
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.
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Affiliation(s)
| | - Robert A. de Man
- Department of Gastroenterology and HepatologyErasmus MC University Medical CenterRotterdamthe Netherlands
| | - Marco Dioguardi Burgio
- Department of RadiologyHauts‐de‐SeineUniversity Hospitals Paris Nord Val de SeineBeaujon, APHPClichyFrance,Centre de Recherche sur l'inflammation (CRI)INSERM U1149et Université de ParisParisFrance
| | - Valerie Vilgrain
- Department of RadiologyHauts‐de‐SeineUniversity Hospitals Paris Nord Val de SeineBeaujon, APHPClichyFrance,Centre de Recherche sur l'inflammation (CRI)INSERM U1149et Université de ParisParisFrance
| | - Jessica Zucman‐Rossi
- Centre de Recherche des CordeliersSorbonne Université, INSERMUniversité de ParisParisFrance,Oncology DepartmentAPHPHôpital européen Georges PompidouParisFrance
| | - Jan N. M. Ijzermans
- Department of SurgeryErasmus MC University Medical CenterRotterdamthe Netherlands
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Taj H, Comba I, Kumar S, Lakhinder B. Extracapsular Hepatocellular Adenoma: A Diagnostic Dilemma. Cureus 2020; 12:e8928. [PMID: 32760628 PMCID: PMC7392356 DOI: 10.7759/cureus.8928] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/29/2020] [Accepted: 06/22/2020] [Indexed: 11/07/2022] Open
Abstract
Hepatocellular adenoma (HCA) is a benign neoplasm of the hepatic parenchyma. The use of oral contraceptives (OCP) in women is the most well-established risk for the development of HCA. HCA commonly presents as an intracapsular mass of the liver but there are very few cases of extracapsular HCA. This is a case of a middle-aged female who presented to the emergency department with left shoulder pain and epigastric tenderness on physical exam. Subsequent imaging of the abdomen revealed a mass arising from the anterior wall of the stomach, with evidence of surrounding hemorrhage. The patient underwent exploratory laparotomy that revealed free blood in the peritoneum and a hemorrhagic mass arising from the stomach wall. The mass was successfully removed with no postoperative complications. Histopathological examination of the mass was consistent with an infarcted inflammatory HCA. This case illustrates this unusual presentation of a rare diagnosis.
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Affiliation(s)
- Hiffsa Taj
- Internal Medicine, University of Central Florida College of Medicine, Orlando, USA
| | - Isin Comba
- Internal Medicine, University of Central Florida College of Medicine, Orlando, USA
| | - Sundeep Kumar
- Cardiovascular Disease, Saint Louis University Hospital, St. Louis, USA
- Internal Medicine, University of Central Florida College of Medicine, Orlando, USA
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Agostini CH, Ribeiro OD, Fernandes A, Caroli-Bottino A, Pannain VL. Relevance of morphological features for hepatocellular adenoma classification in pathology practice. SURGICAL AND EXPERIMENTAL PATHOLOGY 2020. [DOI: 10.1186/s42047-020-00061-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Abstract
Background
Gene mutations correlated with histological and immunohistochemical phenotypes of hepatocellular adenoma were recently identified. Based on these findings, four adenoma subtypes were distinguished. We classify hepatocellular adenoma (HCA) into subtypes based on histologic and immunohistochemical findings and verify the contribution of histological features in pathology practice.
Methods
Thirty hepatocellular adenomas were classified in subtypes. Sinusoidal dilatation, ductular reaction, pseudoportal tracts, pseudoglands, steatosis, inflammatory infiltrate and cellular atypia were analyzed, as well as liver fatty acid binding protein, β catenin, serum amyloid A, glutamine synthetase, and C-reactive protein antibodies.
Results
Histologically, eleven adenomas were classified as HNF1A inactivated (HHCA), five were β-catenin-activated (bHCA) and fourteen were inflammatory adenoma (IHCA). Steatosis was found in all HHCA and was predominantly severe. Sinusoidal dilatation and inflammatory infiltrate were present in all IHCA. Ductular reaction, pseudoportal tracts and cellular atypia were observed in 71.4, 85.7 and 42.8%, respectively. Pseudoglands were present in 60% and cellular atypia in 80% of bHCA. According to immunohistochemistry, 11 were HHCA; 1 was bHCA; 17 were IHCA, among which 5 were β-catenin activated IHCA; and 1 was unclassified UHCA (UHCA). Superior concordance between the histological and immunohistochemical classifications was found for HHCA (К = 0.854) and IHCA (К = 0.657).
Conclusion
Approximately 90% of adenomas may be diagnosed by subgroup based only on morphological features. When aberrant β catenin nuclear staining is not found, glutamine synthetase positivity is useful for diagnosis, although supplementary molecular analysis may be necessary.
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35
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Gonçalves DL, Leite JP, Silva R, Pissarra AP, Caetano Oliveira R, Silva D. Hepatic Adenomatosis: A Challenging Liver Disease. GE-PORTUGUESE JOURNAL OF GASTROENTEROLOGY 2019; 27:37-42. [PMID: 31970239 DOI: 10.1159/000500144] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/22/2019] [Accepted: 03/29/2019] [Indexed: 02/04/2023]
Abstract
Hepatic adenomatosis is defined as the presence of 10 or more adenomas in an otherwise normal liver. Half of the cases are clinically silent and detected incidentally in imaging exams. A 42-year-old woman with previous history of arterial hypertension and mixed dyslipidemia had multiple liver nodules incidentally identified in an abdominal computed tomography scan. She was asymptomatic and her physical examination was unremarkable but laboratory analysis revealed increased alkaline phosphatase and mildly persistent elevated systemic inflammatory markers. A subsequent hepatic magnetic resonance imaging (MRI) suggested the diagnosis of hepatic adenomatosis and the liver biopsy confirmed the presence of inflammatory adenomas. The patient stopped oral contraception and, at 6 months of follow-up, laboratory inflammatory markers had normalized. She is now under biannual follow-up with MRI and alpha-fetoprotein dosing. This case provides an example of the complex management of this disease in terms of diagnosis, treatment, and follow-up.
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Affiliation(s)
- Diana Leite Gonçalves
- Department of Internal Medicine, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal
| | - José Pedro Leite
- Department of Internal Medicine, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal
| | - Rafael Silva
- Department of Internal Medicine, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal
| | - António Pedro Pissarra
- Department of Radiology, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal
| | - Rui Caetano Oliveira
- Department of Anatomical Pathology, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal
| | - Dilva Silva
- Department of Internal Medicine, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal
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Garcovich M, Faccia M, Meloni F, Bertolini E, de Sio I, Calabria G, Francica G, Vidili G, Riccardi L, Zocco MA, Ainora ME, Ponziani FR, De Gaetano AM, Gasbarrini A, Rapaccini GL, Pompili M. Contrast-enhanced ultrasound patterns of hepatocellular adenoma: an Italian multicenter experience. J Ultrasound 2019; 22:157-165. [PMID: 30306412 PMCID: PMC6531526 DOI: 10.1007/s40477-018-0322-5] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2018] [Accepted: 09/14/2018] [Indexed: 02/08/2023] Open
Abstract
PURPOSE Hepatocellular adenoma (HCA) is a rare benign monoclonal neoplasm, recently categorized on genetic and histopathological basis into four subtypes with different biological behaviors. Since contrast-enhanced ultrasonography (CEUS) is nowadays a well-established technique for liver nodule characterization, the aim of our study was to assess CEUS features of HCAs to identify criteria that correlate with different HCA subtypes as compared to histopathologic examination and other imaging modalities. METHODS We retrospectively analyzed data of patients with histology-proven HCA who underwent CEUS, computed tomography or magnetic resonance imaging (MRI) in seven different Italian ultrasound units. RESULTS The study enrolled 19 patients (16 females; 69% with concomitant/prior use of oral contraceptives): the mean size of all HCAs was 4.2 cm (range 1.6-7.1 cm); 14/19 had inflammatory HCAs (I-HCA), 1/19 β-catenin-activated HCA, and the others unclassified HCAs. On CEUS, during the arterial phase, all but one HCA displayed a rapid enhancement, with 89% of these showing centripetal and 11% centrifugal filling pattern, whereas during the portal and late venous phase 58% of HCA showed washout and the remaining 42% displayed persistent enhancement. In particular, among I-HCAs 7/14 showed no washout, 3/14 and 4/14 showed washout in the portal or late phase, respectively. CONCLUSIONS This dataset represents one of the few published experiences on HCAs and CEUS in Italy and shows that HCAs are hypervascularized in the arterial phase usually with a centripetal flow pattern and have a heterogeneous behavior in portal and late phase. In particular, occurrence of delayed washout on CEUS but not on MRI is frequently observed in the subtype of I-HCA.
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Affiliation(s)
- Matteo Garcovich
- Department of Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Catholic University of Sacred Heart, Largo A. Gemelli 8, 00168, Rome, Italy.
| | - Mariella Faccia
- Department of Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Catholic University of Sacred Heart, Largo A. Gemelli 8, 00168, Rome, Italy
| | - Franca Meloni
- Department of Interventional Ultrasound, Casa di Cura Igea, Milan, Italy
- Department of Radiology, University of Wisconsin-Madison, Madison, USA
| | - Emanuela Bertolini
- Department of Internal Medicine, Hepatology and Gastroenterology, San Paolo Hospital, Università degli Studi di Milano, Milan, Italy
| | - Ilario de Sio
- Hepatogastroenterology Unit, Università degli Studi della Campania Luigi Vanvitelli, Naples, Italy
| | - Giosuele Calabria
- IX Interventional Ultrasound Unit for Infectious Diseases, AORN dei Colli, Cotugno Hospital, Naples, Italy
| | - Giampiero Francica
- Interventional Ultrasound Unit, Pineta Grande Hospital, Castel Volturno, Italy
| | - Gianpaolo Vidili
- Department of Clinical and Experimental Medicine, University of Sassari, Sassari, Italy
| | - Laura Riccardi
- Department of Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Catholic University of Sacred Heart, Largo A. Gemelli 8, 00168, Rome, Italy
| | - Maria Assunta Zocco
- Department of Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Catholic University of Sacred Heart, Largo A. Gemelli 8, 00168, Rome, Italy
| | - Maria Elena Ainora
- Department of Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Catholic University of Sacred Heart, Largo A. Gemelli 8, 00168, Rome, Italy
| | - Francesca Romana Ponziani
- Department of Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Catholic University of Sacred Heart, Largo A. Gemelli 8, 00168, Rome, Italy
| | - Anna Maria De Gaetano
- Department of Radiology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Catholic University of Sacred Heart, Rome, Italy
| | - Antonio Gasbarrini
- Department of Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Catholic University of Sacred Heart, Largo A. Gemelli 8, 00168, Rome, Italy
| | - Gian Ludovico Rapaccini
- Department of Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Catholic University of Sacred Heart, Largo A. Gemelli 8, 00168, Rome, Italy
| | - Maurizio Pompili
- Department of Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Catholic University of Sacred Heart, Largo A. Gemelli 8, 00168, Rome, Italy
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Bleeding Liver Masses: Imaging Features With Pathologic Correlation and Impact on Management. AJR Am J Roentgenol 2019; 213:8-16. [PMID: 30973778 DOI: 10.2214/ajr.19.21240] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
OBJECTIVE. The purposes of this article are to discuss a variety of liver masses that can present with hemorrhage, including their characteristic imaging features, and to propose a diagnostic approach. CONCLUSION. A broad spectrum of pathologic conditions can present as spontaneous hemorrhage within or surrounding the liver and may present acutely or as a chronic or incidental finding. Imaging characteristics and clinical history can often narrow the differential diagnosis and guide management.
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Nemoto S, Ariizumi SI, Kotera Y, Omori A, Yamashita S, Kato TA, Aoyama S, Egawa H, Yamamoto M. Inflammatory hepatocellular adenoma in a patient with Turner's syndrome: A case report. Int J Surg Case Rep 2019; 56:5-9. [PMID: 30798096 PMCID: PMC6389595 DOI: 10.1016/j.ijscr.2019.02.017] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2018] [Revised: 02/07/2019] [Accepted: 02/08/2019] [Indexed: 02/09/2023] Open
Abstract
INTRODUCTION Hepatocellular adenoma (HCA) is a rare benign tumor and is related to the use of an oral contraceptive pill. Turner's syndrome requires various hormone replacement therapies, including the pill which is used as a female hormone replacement therapy. Herein we report a case of Turner's syndrome with HCA treated by liver segmentectomy. PRESENTATION OF CASE A 36-year-old woman with Turner's syndrome was treated with oral contraceptive pills as a female hormone replacement therapy for 20 years. She presented with fatigue and liver tumor. Liver tumors in the posterior lobe measuring 60 mm and 10 mm in diameter were detected on CT; hence, she was referred to our department. Both the tumors showed high intensity in the arterial phase, iso-intensity in the portal and late phases, and low intensity in the hepatobiliary phase on Gb-EOB-MRI. She was diagnosed with multiple HCAs and underwent segmentectomy Section 7. Pathologically, both the tumors were diagnosed as HCAs, and inflammatory markers were detected by immunohistochemistry. Thirteen months postoperatively, she was doing well and there was no evidence of recurrence of HCA without the pill. DISCUSSION There is only one report of HCA in patients with TS (Espat et al., 2000). We reported a case of multiple HCAs in a patient with TS underwent hepatectomy. CONCLUSION With the use of the contraceptive pill as a long-term female hormone replacement therapy for Turner's syndrome, careful attention is required for HCA.
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Affiliation(s)
- Satoshi Nemoto
- Department of Gastroenterology Surgery, Tokyo Women's Medical University, Japan.
| | - Shun-Ichi Ariizumi
- Department of Gastroenterology Surgery, Tokyo Women's Medical University, Japan.
| | - Yoshihito Kotera
- Department of Gastroenterology Surgery, Tokyo Women's Medical University, Japan
| | - Akiko Omori
- Department of Gastroenterology Surgery, Tokyo Women's Medical University, Japan
| | - Shingo Yamashita
- Department of Gastroenterology Surgery, Tokyo Women's Medical University, Japan
| | - Taka-Aki Kato
- Department of Gastroenterology Surgery, Tokyo Women's Medical University, Japan
| | - Shota Aoyama
- Department of Gastroenterology Surgery, Tokyo Women's Medical University, Japan
| | - Hiroto Egawa
- Department of Gastroenterology Surgery, Tokyo Women's Medical University, Japan
| | - Masakazu Yamamoto
- Department of Gastroenterology Surgery, Tokyo Women's Medical University, Japan
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Sciarra A, Schmidt S, Pellegrinelli A, Maggioni M, Dondossola D, Pasquier J, Cigala C, Tosi D, Halkic N, Bulfamante G, Viale G, Bosari S, Balabaud C, Bioulac-Sage P, Sempoux C. OATPB1/B3 and MRP3 expression in hepatocellular adenoma predicts Gd-EOB-DTPA uptake and correlates with risk of malignancy. Liver Int 2019; 39:158-167. [PMID: 30218633 DOI: 10.1111/liv.13964] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2018] [Revised: 08/22/2018] [Accepted: 09/07/2018] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND AIMS Hepatobiliary phase (HBP) Gd-EOB-DTPA-enhanced magnetic resonance imaging (MRI) has increased the accuracy in differentiating focal nodular hyperplasia (FNH) and hepatocellular adenoma (HCA). However, the ability of this technique to distinguish HCA subtypes remains controversial. The aim of this study was to investigate the expression of hepatocyte transporters (OATPB1/B3, MRP2, MRP3) in HCA subtypes, hence to understand their MRI signal intensity on HBP Gd-EOB-DTPA-enhanced MRI. METHODS By means of immunohistochemistry (IHC), we scored the expression of OATPB1/B3, MRP2 and MRP3, in resected specimens of FNH (n = 40), subtyped HCA (n = 58) and HCA with focal malignant transformation (HCA-HCC, n = 4). Results were validated on a supplementary set of FNH (n = 6), subtyped HCA (n = 17) and HCA-HCC (n = 1) with Gd-EOB-DTPA MR images. RESULTS All FNH showed a preserved expression of hepatocytes transporters. Beta-catenin-activated HCA (at highest risk of malignant transformation) and HCA-HCC were characterized by preserved/increased OATPB1/B3 expression (predictor of hyperintensity on HBP), as opposed to other HCA subtypes (P < 0.01) that mostly showed OATPB1/B3 absence (predictor of hypointensity on HBP). HCA-HCC showed an additional MRP3 overexpressed profile (P < 0.01). On HBP Gd-EOB-DTPA-enhanced MRI, FNH and HCA signal intensity reflected the profile predicted by their specific OATPB1/B3 tissue expression. The hyperintense vs hypointense HBP signal criterion was able to distinguish all higher risk HCA and HCA-HCC (100% accuracy). CONCLUSIONS OATPB1/B3 and MRP3 IHC and signal intensity on HBP Gd-EOB-DTPA-enhanced MRI can help to stratify HCA according to their risk of malignant transformation.
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Affiliation(s)
- Amedeo Sciarra
- Service of Clinical Pathology, Institute of Pathology, Lausanne University Hospital, Lausanne, Switzerland.,Pathology, Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico, University of Milan, Milan, Italy
| | - Sabine Schmidt
- Department of Diagnostic and Interventional Radiology, Lausanne University Hospital, Lausanne, Switzerland
| | | | - Marco Maggioni
- Pathology, Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico, University of Milan, Milan, Italy
| | - Daniele Dondossola
- Liver Transplant and General Surgery Unit, Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico, Milan, Italy
| | - Jerome Pasquier
- Institute for Social and Preventive Medicine, Lausanne University Hospital, Lausanne, Switzerland
| | - Claudia Cigala
- Unit of Pathology, San Paolo Hospital Medical School, Department of Health Sciences, University of Milan, Milan, Italy
| | - Delfina Tosi
- Unit of Pathology, San Paolo Hospital Medical School, Department of Health Sciences, University of Milan, Milan, Italy
| | - Nermin Halkic
- Department of Visceral Surgery, Lausanne University Hospital, Lausanne, Switzerland
| | - Gaetano Bulfamante
- Unit of Pathology, San Paolo Hospital Medical School, Department of Health Sciences, University of Milan, Milan, Italy
| | - Giuseppe Viale
- European Institute of Oncology, University of Milan, Milan, Italy
| | - Silvano Bosari
- Pathology, Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico, University of Milan, Milan, Italy
| | - Charles Balabaud
- Pathology Department, Inserm, UMR-1053, CHU de Bordeaux, Pellegrin Hospital, Bordeaux, France
| | - Paulette Bioulac-Sage
- Pathology Department, Inserm, UMR-1053, CHU de Bordeaux, Pellegrin Hospital, Bordeaux, France
| | - Christine Sempoux
- Service of Clinical Pathology, Institute of Pathology, Lausanne University Hospital, Lausanne, Switzerland
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40
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Dokmak S, Aussilhou B, Rasoaherinomenjanahary F, Ronot M, Dahdouh R, Ftériche FS, Cauchy F, Paradis V, Belghiti J, Soubrane O. Hemorrhage of hepatocellular adenoma: a complication that can be treated by conservative management without surgery. HPB (Oxford) 2018; 20:1198-1205. [PMID: 31217088 DOI: 10.1016/j.hpb.2018.06.1796] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2018] [Revised: 06/03/2018] [Accepted: 06/08/2018] [Indexed: 02/06/2023]
Abstract
BACKGROUND Hemorrhage is the main complication of hepatocellular adenoma (HCA). The aim of this study was to describe a single center's evolving management of patients with hemorrhagic HCA. METHOD Between 1990 and 2013, all patients with hemorrhagic HCA were included. During the study period, the management evolved from urgent surgery (period <2004) to arterial embolization with (period, 2004-2010) or without (period > 2010) delayed resection. RESULTS A total of 56 patients were identified. The median (range) size of HCA and the hematoma was 80 mm (35-160) and 50 mm (10-160). Patients were treated by urgent resection (group 1, n = 6), delayed resection with or without embolization (group 2, n = 43) and systematic embolization without surgery (group 3, n = 7). Embolization was performed in 0/6, 15/43 and 7/7 in groups 1, 2 and 3. Urgent resection was associated with higher morbidity (p < 0.001). Complete necrosis was observed in 0/6, 13/43 and 3/7 patients, and on histology it was associated with embolization (p = 0.001), a hematoma-tumor ratio > 60% (p = 0.046) and a cystic non-viable lesion before surgery (p < 0.001). CONCLUSION Hemodynamic stability can be achieved in patients presenting with hemorrhagic HCA by none surgical means. Subsequent surgery can be completely avoided with such an approach in up to 40% of patients.
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Affiliation(s)
- Safi Dokmak
- Department of HPB Surgery and Liver Transplantation, Beaujon Hospital, Clichy, France.
| | - Béatrice Aussilhou
- Department of HPB Surgery and Liver Transplantation, Beaujon Hospital, Clichy, France
| | | | - Maxime Ronot
- Department of Radiology, Beaujon Hospital, Clichy, France
| | - Rafik Dahdouh
- Department of HPB Surgery and Liver Transplantation, Beaujon Hospital, Clichy, France
| | - Fadhel S Ftériche
- Department of HPB Surgery and Liver Transplantation, Beaujon Hospital, Clichy, France
| | - François Cauchy
- Department of HPB Surgery and Liver Transplantation, Beaujon Hospital, Clichy, France
| | - Valérie Paradis
- Department of Pathology, Beaujon Hospital, Assistance Publique Hôpitaux de Paris, University Paris VII, Clichy, France
| | - Jacques Belghiti
- Department of HPB Surgery and Liver Transplantation, Beaujon Hospital, Clichy, France
| | - Olivier Soubrane
- Department of HPB Surgery and Liver Transplantation, Beaujon Hospital, Clichy, France
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41
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Sexual dimorphism in hepatitis B and C and hepatocellular carcinoma. Semin Immunopathol 2018; 41:203-211. [PMID: 30498927 DOI: 10.1007/s00281-018-0727-4] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2018] [Accepted: 11/04/2018] [Indexed: 12/14/2022]
Abstract
The incidence of viral hepatitis B or C (HBV/HCV) infection and hepatocellular carcinoma is higher in male compared to female populations, showing a faster disease progression and results in a worse overall survival. Indeed, women are in general better protected from viral infections and show a lower risk of death from malignant cancer in comparison to men. Females mount stronger innate and adaptive immune responses than males, and therefore, most of the autoimmune diseases occur predominantly in females. Next to occupational and/or behavioral factors, cellular and molecular differences between the two sexes contribute to this observation. In this review, we will discuss underlying mechanisms that are important for the observed sex-related differences in liver diseases. A better appreciation of these differences between the two sexes might be of value for better and gender-specific treatment options.
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42
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Brooks ED, Landau DJ, Everitt JI, Brown TT, Grady KM, Waskowicz L, Bass CR, D'Angelo J, Asfaw YG, Williams K, Kishnani PS, Koeberl DD. Long-term complications of glycogen storage disease type Ia in the canine model treated with gene replacement therapy. J Inherit Metab Dis 2018; 41:965-976. [PMID: 30043186 PMCID: PMC6328337 DOI: 10.1007/s10545-018-0223-y] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2017] [Revised: 06/09/2018] [Accepted: 06/19/2018] [Indexed: 12/28/2022]
Abstract
BACKGROUND Glycogen storage disease type Ia (GSD Ia) in dogs closely resembles human GSD Ia. Untreated patients with GSD Ia develop complications associated with glucose-6-phosphatase (G6Pase) deficiency. Survival of human patients on intensive nutritional management has improved; however, long-term complications persist including renal failure, nephrolithiasis, hepatocellular adenomas (HCA), and a high risk for hepatocellular carcinoma (HCC). Affected dogs fail to thrive with dietary therapy alone. Treatment with gene replacement therapy using adeno-associated viral vectors (AAV) expressing G6Pase has greatly prolonged life and prevented hypoglycemia in affected dogs. However, long-term complications have not been described to date. METHODS Five GSD Ia-affected dogs treated with AAV-G6Pase were evaluated. Dogs were euthanized due to reaching humane endpoints related to liver and/or kidney involvement, at 4 to 8 years of life. Necropsies were performed and tissues were analyzed. RESULTS Four dogs had liver tumors consistent with HCA and HCC. Three dogs developed renal failure, but all dogs exhibited progressive kidney disease histologically. Urolithiasis was detected in two dogs; uroliths were composed of calcium oxalate and calcium phosphate. One affected and one carrier dog had polycystic ovarian disease. Bone mineral density was not significantly affected. CONCLUSIONS Here, we show that the canine GSD Ia model demonstrates similar long-term complications as GSD Ia patients in spite of gene replacement therapy. Further development of gene therapy is needed to develop a more effective treatment to prevent long-term complications of GSD Ia.
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Affiliation(s)
- Elizabeth D Brooks
- Division of Medical Genetics, Duke University Medical Center (DUMC), Box 103856, Durham, NC, 27710, USA
- Division of Laboratory Animal Resources, Duke University Medical Center, Durham, NC, USA
| | - Dustin J Landau
- Division of Medical Genetics, Duke University Medical Center (DUMC), Box 103856, Durham, NC, 27710, USA
| | - Jeffrey I Everitt
- Department of Pathology, Duke University Medical Center, Durham, NC, USA
| | - Talmage T Brown
- College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA
| | - Kylie M Grady
- Division of Medical Genetics, Duke University Medical Center (DUMC), Box 103856, Durham, NC, 27710, USA
| | - Lauren Waskowicz
- Division of Medical Genetics, Duke University Medical Center (DUMC), Box 103856, Durham, NC, 27710, USA
| | - Cameron R Bass
- Department of Biomedical Engineering, Duke University Medical Center, Durham, NC, USA
| | - John D'Angelo
- Department of Biomedical Engineering, Duke University Medical Center, Durham, NC, USA
| | - Yohannes G Asfaw
- Division of Laboratory Animal Resources, Duke University Medical Center, Durham, NC, USA
| | - Kyha Williams
- Division of Laboratory Animal Resources, Duke University Medical Center, Durham, NC, USA
| | - Priya S Kishnani
- Division of Medical Genetics, Duke University Medical Center (DUMC), Box 103856, Durham, NC, 27710, USA
| | - Dwight D Koeberl
- Division of Medical Genetics, Duke University Medical Center (DUMC), Box 103856, Durham, NC, 27710, USA.
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Gryspeerdt F, Aerts R. Laparoscopic liver resection for hemorrhagic hepatocellular adenoma in a pregnant patient. Acta Chir Belg 2018; 118:322-325. [PMID: 28982300 DOI: 10.1080/00015458.2017.1379790] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
INTRODUCTION Hepatocellular adenoma (HCA) is a benign neoplasm of the liver, however, with a potential for life-threatening hemorrhage. The unpredictable course during pregnancy poses a clinical dilemma in the pregnant patient. Intra-peritoneal rupture may lead to life-threatening situations with adverse outcome for mother and unborn child. A pre-emptive strategy with adequate treatment before pregnancy is strongly advised. However, the strategy for treating symptomatic HCA during pregnancy remains challenging as experience is limited. CASE PRESENTATION A 31-year-old pregnant patient at the gestational age of 17 weeks presented with an acute episode of right upper abdomen pain. MR-imaging revealed a lesion of 9 cm located in segment III with stigmata of recent hemorrhage. At 18 weeks of gestation, she underwent a semi-elective laparoscopic left lateral sectionectomy. RESULTS Surgery and postoperative recovery were uneventful. Patient was discharged at POD +6. At 40 weeks of gestation, she went in spontaneous labor and delivered a healthy baby. Histological examination confirmed a HCA, inflammatory subtype, showing features of hemorrhage. CONCLUSION In the pregnant patient, HCA represents a significant diagnostic and therapeutic challenge. Anatomically favorable located lesions can be safely managed with laparoscopic liver resection. We suggest that laparoscopic liver resection should be considered as part of the currently available strategies for HCA during pregnancy.
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Affiliation(s)
- F. Gryspeerdt
- Department of Abdominal Surgery, UZ Leuven, Leuven, Belgium
| | - R. Aerts
- Department of Abdominal Surgery, UZ Leuven, Leuven, Belgium
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44
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Ferrell LD, Kakar S, Terracciano LM, Wee A. Tumours and Tumour-like Lesions of the Liver. MACSWEEN'S PATHOLOGY OF THE LIVER 2018:780-879. [DOI: 10.1016/b978-0-7020-6697-9.00013-3] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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45
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Kang HJ, Jeong HJ, Kim SW, Yu E, Lee YJ, Kim SY, Kim J. Hepatocellular Carcinoma Arising in a Huge Hepatocellular Adenoma with Bone Marrow Metaplasia. J Pathol Transl Med 2017; 52:226-231. [PMID: 29281780 PMCID: PMC6056361 DOI: 10.4132/jptm.2017.11.12] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2017] [Accepted: 11/12/2017] [Indexed: 01/29/2023] Open
Abstract
Hepatocellular adenoma (HCA) is the most common type of benign liver tumor, and its major complication is malignant transformation to hepatocellular carcinoma (HCC). Here, we report a case of HCC arising in HCA with bone marrow metaplasia in a 24-year-old Korean woman who presented with abdominal discomfort. A huge liver mass was found on abdominal ultrasonography. She underwent surgical hepatic resection, and the resected specimen was entirely involved by a 20-cm-sized tumor. Histological review revealed a well differentiated HCC arising from inflammatory HCA with β-catenin nuclear positivity and bone marrow metaplasia that contained hematopoietic cells. This case was unique because malignant transformation, inflammatory type HCA, β-catenin nuclear staining, and bone marrow metaplasia were simultaneously observed. Additionally, it should be noted that a large HCA with β-catenin activation can undergo malignant transformation and should be surgically resected in a timely manner.
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Affiliation(s)
- Hyo Jeong Kang
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.,Department of Physiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Hui Jeong Jeong
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - So-Woon Kim
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Eunsil Yu
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.,Department of Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Young-Joo Lee
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - So Yeon Kim
- Department of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jihun Kim
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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47
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Typical and atypical benign liver lesions: A review. Clin Imaging 2017; 44:79-91. [PMID: 28486156 DOI: 10.1016/j.clinimag.2017.05.002] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2017] [Revised: 04/10/2017] [Accepted: 05/01/2017] [Indexed: 02/06/2023]
Abstract
Focal liver lesions are routinely encountered by clinical radiologists and represent a wide spectrum of pathology. Majority of these lesions are likely to be benign in nature, especially in the absence of chronic liver disease or primary cancer. A radiologist must be aware of common and uncommon imaging features of benign lesions across the various imaging modalities. This review discusses pathognomonic imaging features of common benign focal liver lesions seen on ultrasound, computed tomography and magnetic resonance, and adds to existing knowledge with the recent updates to have emerged in this area.
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48
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Venkatesh SK, Hennedige T, Johnson GB, Hough DM, Fletcher JG. Imaging patterns and focal lesions in fatty liver: a pictorial review. Abdom Radiol (NY) 2017; 42:1374-1392. [PMID: 27999887 DOI: 10.1007/s00261-016-1002-6] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
Non-alcoholic fatty liver disease is the most common cause of chronic liver disease and affects nearly one-third of US population. With the increasing trend of obesity in the population, associated fatty change in the liver will be a common feature observed in imaging studies. Fatty liver causes changes in liver parenchyma appearance on imaging modalities including ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI) and may affect the imaging characteristics of focal liver lesions (FLLs). The imaging characteristics of FLLs were classically described in a non-fatty liver. In addition, focal fatty change and focal fat sparing may also simulate FLLs. Knowledge of characteristic patterns of fatty change in the liver (diffuse, geographical, focal, subcapsular, and perivascular) and their impact on the detection and characterization of FLL is therefore important. In general, fatty change may improve detection of FLLs on MRI using fat suppression sequences, but may reduce sensitivity on a single-phase (portal venous) CT and conventional ultrasound. In patients with fatty liver, MRI is generally superior to ultrasound and CT for detection and characterization of FLL. In this pictorial essay, we describe the imaging patterns of fatty change in the liver and its effect on detection and characterization of FLLs on ultrasound, CT, MRI, and PET.
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Affiliation(s)
- Sudhakar K Venkatesh
- Department of Radiology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.
| | - Tiffany Hennedige
- Department of Oncologic Imaging, National Cancer Centre, Singapore, Singapore
| | - Geoffrey B Johnson
- Department of Radiology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA
| | - David M Hough
- Department of Radiology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA
| | - Joel G Fletcher
- Department of Radiology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA
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49
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Hepatocellular adenoma: imaging review of the various molecular subtypes. Clin Radiol 2017; 72:276-285. [DOI: 10.1016/j.crad.2016.12.020] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2016] [Revised: 11/30/2016] [Accepted: 12/22/2016] [Indexed: 02/08/2023]
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50
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EASL Clinical Practice Guidelines on the management of benign liver tumours. J Hepatol 2016; 65:386-98. [PMID: 27085809 DOI: 10.1016/j.jhep.2016.04.001] [Citation(s) in RCA: 317] [Impact Index Per Article: 35.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2016] [Accepted: 04/05/2016] [Indexed: 02/06/2023]
Affiliation(s)
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- European Association for the Study of the Liver (EASL), The EASL Building – Home of European Hepatology, 7 rue Daubin, CH 1203 Geneva, Switzerland.
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