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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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El Ouardi W, El Mansoury FZ, Labbioui R, Benazzouz M. Hepatocellular adenoma with activation of the β-catenin mutation pathway mimicking intrahepatic cholangiocarcinoma: Case report. Radiol Case Rep 2025; 20:521-524. [PMID: 39559499 PMCID: PMC11570408 DOI: 10.1016/j.radcr.2024.10.061] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2024] [Revised: 10/09/2024] [Accepted: 10/10/2024] [Indexed: 11/20/2024] Open
Abstract
Hepatocellular adenomas are relatively rare benign tumors of the liver that primarily develop in young women, particularly those who use oral contraceptive pills. There are 4 distinct subtypes of these tumors. Among them, β-catenin-mutated adenomas constitute approximately 10% to 15% and are notable for their potential to undergo malignant transformation. In this report, we present the case of a young patient who had a 4 cm hepatic lesion. The initial imaging studies, particularly an MRI, suggested that the lesion might be an intrahepatic cholangiocarcinoma. However, upon further histological examination, the lesion was identified as a benign hepatic adenoma, with activation of the β-catenin mutation pathway. Due to the associated risk of malignant transformation, the treatment plan included surgical resection of the adenoma. This approach is critical in managing such lesions to prevent any potential progression to hepatocellular carcinoma.
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Affiliation(s)
- Walid El Ouardi
- Gastroenterology Department, Mohamed V University, faculty of medicine and pharmacy, Rabat, Morocco
| | | | | | - Mustapha Benazzouz
- Department of gastroenterology, International University of Rabat/Riad Annakhil International Polyclinic, Rabat, Morocco
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3
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Lopes SR, Santos IC, Teixeira M, Sequeira C, Carvalho AM, Gamito É. Hepatocellular Adenoma: A Life-Threatening Presentation of a Rare Liver Tumor - Case Report and Literature Review. GE PORTUGUESE JOURNAL OF GASTROENTEROLOGY 2024; 31:443-448. [PMID: 39633913 PMCID: PMC11614446 DOI: 10.1159/000538340] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/11/2023] [Accepted: 02/19/2024] [Indexed: 12/07/2024]
Abstract
Hepatocellular adenoma is a rare benign liver tumor that occurs predominantly in young women who use exogenous estrogens. We describe a case of a 40-year-old woman on birth control pill who presented with acute right hypochondrial pain and signs of hemodynamical instability triggered by a large bleeding tumor in the right liver lobe. Arterial embolization was performed with cessation of bleeding. To determine etiology, magnetic resonance imaging was conducted with findings suggestive of a hepatocellular adenoma. The tumor was surgically resected, and histologic examination made the definite diagnosis of an inflammatory hepatocellular adenoma. This is a noteworthy case of a rare but potentially fatal complication of liver tumors, whose diagnosis requires a high index of suspicion. Clinicians should consider this diagnosis in young women on oral contraceptive pills who present with severe unexplained abdominal pain and hemodynamical instability. This case aimed to raise awareness of this condition, while reviewing important aspects concerning the management of hepatocellular adenomas.
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Affiliation(s)
- Sara Ramos Lopes
- Gastrenterology Department, Centro Hospitalar de Setúbal, Setúbal, Portugal
| | - Inês Costa Santos
- Gastrenterology Department, Centro Hospitalar de Setúbal, Setúbal, Portugal
| | - Madalena Teixeira
- Gastrenterology Department, Centro Hospitalar de Setúbal, Setúbal, Portugal
| | - Cristiana Sequeira
- Gastrenterology Department, Centro Hospitalar de Setúbal, Setúbal, Portugal
| | | | - Élia Gamito
- Gastrenterology Department, Centro Hospitalar de Setúbal, Setúbal, Portugal
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4
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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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5
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Oudmaijer CAJ, Sprakel J, Sprengers D, Wiese KA, Tintel NV, Franken JI, Terkivatan T, Porte RJ, IJzermans JNM. Hepatocellular adenomas with severe intra-abdominal bleeding, related to an underlying coagulation disorder: a case report. J Med Case Rep 2024; 18:367. [PMID: 39135148 PMCID: PMC11321172 DOI: 10.1186/s13256-024-04709-7] [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: 03/26/2024] [Accepted: 07/18/2024] [Indexed: 08/15/2024] Open
Abstract
BACKGROUND Hepatocellular adenoma is a rare benign liver tumor. Typically, hepatocellular adenomas are solitary and are found in young women who use estrogen-containing contraceptives. The occurrence of multiple hepatocellular adenoma has been linked to higher body mass index, and as the prevalence of overweight increases, multiple hepatocellular adenomas are seen more often. An hepatocellular adenoma does not always necessitate treatment, as they can regress under conservative strategies. In incidental cases, an adenoma presents owing to bleeding, which is mostly self-limiting. If it is not, embolization of hepatic involved vessels is indicated. CASE PRESENTATION In this case report, we discuss a 42-year old Caucasian woman with multiple hepatocellular bleeds, treated by multiple endovascular procedures. After the first embolization of an adenoma in the right liver lobe, a second bleed occurred in the left lobe, necessitating additional endovascular intervention. During admittance, treatment was complicated by pulmonary embolism and a pneumonia. During follow-up, our patient was diagnosed with antiphospholipid syndrome. CONCLUSION Hepatocellular adenoma is a rare diagnosis that requires centralized expertise. This particular case illustrates the complexity of treatment strategies for associated intra-abdominal bleeding and possible complications. Although liver adenoma is often an incidental finding, it can also result in significant morbidity. Centralization of treatment leads to expertise in managing complex treatment strategies.
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Affiliation(s)
- C A J Oudmaijer
- Erasmus MC Transplant Institute, Department of Surgery, Division of Hepatobiliary and Transplantation Surgery, University Medical Center Rotterdam, Office RG-220, Dr. Molewaterplein 40, 3015 GD, Rotterdam, the Netherlands.
- Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.
- Oncode Institute, Utrecht, the Netherlands.
| | - J Sprakel
- Erasmus MC Transplant Institute, Department of Surgery, Division of Hepatobiliary and Transplantation Surgery, University Medical Center Rotterdam, Office RG-220, Dr. Molewaterplein 40, 3015 GD, Rotterdam, the Netherlands
| | - D Sprengers
- Department of Gastro-Enterology, Division of Hepatology, University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - K A Wiese
- Department of Radiology, University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - N Vogelaar- Tintel
- Erasmus MC Transplant Institute, Department of Surgery, Division of Hepatobiliary and Transplantation Surgery, University Medical Center Rotterdam, Office RG-220, Dr. Molewaterplein 40, 3015 GD, Rotterdam, the Netherlands
| | - J I Franken
- Erasmus MC Transplant Institute, Department of Surgery, Division of Hepatobiliary and Transplantation Surgery, University Medical Center Rotterdam, Office RG-220, Dr. Molewaterplein 40, 3015 GD, Rotterdam, the Netherlands
| | - T Terkivatan
- Erasmus MC Transplant Institute, Department of Surgery, Division of Hepatobiliary and Transplantation Surgery, University Medical Center Rotterdam, Office RG-220, Dr. Molewaterplein 40, 3015 GD, Rotterdam, the Netherlands
| | - R J Porte
- Erasmus MC Transplant Institute, Department of Surgery, Division of Hepatobiliary and Transplantation Surgery, University Medical Center Rotterdam, Office RG-220, Dr. Molewaterplein 40, 3015 GD, Rotterdam, the Netherlands
| | - J N M IJzermans
- Erasmus MC Transplant Institute, Department of Surgery, Division of Hepatobiliary and Transplantation Surgery, University Medical Center Rotterdam, Office RG-220, Dr. Molewaterplein 40, 3015 GD, Rotterdam, the Netherlands
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6
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Hashimoto S, Hasan MDN, Arif M, Nozaki N, Husna AA, Furusawa Y, Sogawa T, Takahashi K, Kuramoto T, Noguchi A, Takahashi M, Yamato O, Rahman MM, Miura N. Aberrantly Expressed tRNA-Val Fragments Can Distinguish Canine Hepatocellular Carcinoma from Canine Hepatocellular Adenoma. Genes (Basel) 2024; 15:1024. [PMID: 39202384 PMCID: PMC11353709 DOI: 10.3390/genes15081024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2024] [Revised: 08/01/2024] [Accepted: 08/02/2024] [Indexed: 09/03/2024] Open
Abstract
Hepatocellular adenoma (HCA) and hepatocellular carcinoma (HCC) can be difficult to differentiate but must be diagnosed correctly as treatment and prognosis for these tumors differ markedly. Relevant diagnostic biomarkers are thus needed, and those identified in dogs may have utility in human medicine because of the similarities between human and canine HCA and HCC. A tRNA-derived fragment (tRF), tRNA-Val, is a promising potential biomarker for canine mammary gland tumors but has not previously been investigated in hepatic tumors. Accordingly, we aimed to elucidate the potential utility of tRNA-Val as a biomarker for canine HCA and HCC using clinical samples (tumor tissue and plasma extracellular vesicles [EVs]) and tumor cell lines with qRT-PCR assays. We also investigated relevant functions and signaling pathways with bioinformatic analyses (Gene Ontology and Kyoto Encyclopedia of Genes and Genomes). tRNA-Val was markedly downregulated in HCC tumor tissue versus HCA tumor tissue and normal liver tissue, and a similar trend was shown in plasma EVs and HCC cell lines versus healthy controls. Based on areas under the receiver operating characteristic curves (AUCs), tRNA-Val significantly distinguished HCC (AUC = 1.00, p = 0.001) from healthy controls in plasma EVs and HCC from HCA (AUC = 0.950, p = 0.01). Bioinformatics analysis revealed that tRNA-Val may be primarily involved in DNA repair, mRNA processing, and splicing and may be linked to the N-glycan and ubiquitin-mediated proteasome pathways. This is the first report on the expression of tRNA-Val in canine HCC and HCA and its possible functions and signaling pathways. We suggest that tRNA-Val could be a promising novel biomarker to distinguish canine HCC from HCA. This study provides evidence for a greater understanding of the role played by tRNA-Val in the development of canine HCC.
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MESH Headings
- Animals
- Dogs
- Carcinoma, Hepatocellular/genetics
- Carcinoma, Hepatocellular/veterinary
- Carcinoma, Hepatocellular/pathology
- Carcinoma, Hepatocellular/metabolism
- Liver Neoplasms/genetics
- Liver Neoplasms/veterinary
- Liver Neoplasms/pathology
- Biomarkers, Tumor/genetics
- Dog Diseases/genetics
- Dog Diseases/diagnosis
- Adenoma, Liver Cell/genetics
- Adenoma, Liver Cell/veterinary
- Adenoma, Liver Cell/pathology
- Adenoma, Liver Cell/metabolism
- Adenoma, Liver Cell/diagnosis
- Gene Expression Regulation, Neoplastic
- Diagnosis, Differential
- Cell Line, Tumor
- Female
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Affiliation(s)
- Saki Hashimoto
- Joint Graduate School of Veterinary Medicine, Kagoshima University, 1-21-24 Korimoto, Kagoshima 890-0065, Japan
| | - MD Nazmul Hasan
- Joint Graduate School of Veterinary Medicine, Kagoshima University, 1-21-24 Korimoto, Kagoshima 890-0065, Japan
| | - Mohammad Arif
- Joint Graduate School of Veterinary Medicine, Kagoshima University, 1-21-24 Korimoto, Kagoshima 890-0065, Japan
| | - Nobuhiro Nozaki
- Joint Graduate School of Veterinary Medicine, Kagoshima University, 1-21-24 Korimoto, Kagoshima 890-0065, Japan
| | - Al Asmaul Husna
- Joint Faculty of Veterinary Medicine, Kagoshima University, 1-21-24 Korimoto, Kagoshima 890-0065, Japan
| | - Yu Furusawa
- Joint Faculty of Veterinary Medicine, Kagoshima University, 1-21-24 Korimoto, Kagoshima 890-0065, Japan
| | - Takeshi Sogawa
- Joint Faculty of Veterinary Medicine, Kagoshima University, 1-21-24 Korimoto, Kagoshima 890-0065, Japan
| | - Kaori Takahashi
- Joint Faculty of Veterinary Medicine, Kagoshima University, 1-21-24 Korimoto, Kagoshima 890-0065, Japan
| | - Tomohide Kuramoto
- Joint Faculty of Veterinary Medicine, Kagoshima University, 1-21-24 Korimoto, Kagoshima 890-0065, Japan
| | - Aki Noguchi
- Joint Faculty of Veterinary Medicine, Kagoshima University, 1-21-24 Korimoto, Kagoshima 890-0065, Japan
| | - Masashi Takahashi
- Joint Graduate School of Veterinary Medicine, Kagoshima University, 1-21-24 Korimoto, Kagoshima 890-0065, Japan
- Joint Faculty of Veterinary Medicine, Kagoshima University, 1-21-24 Korimoto, Kagoshima 890-0065, Japan
| | - Osamu Yamato
- Joint Graduate School of Veterinary Medicine, Kagoshima University, 1-21-24 Korimoto, Kagoshima 890-0065, Japan
- Joint Faculty of Veterinary Medicine, Kagoshima University, 1-21-24 Korimoto, Kagoshima 890-0065, Japan
| | - Md Mahfuzur Rahman
- Joint Faculty of Veterinary Medicine, Kagoshima University, 1-21-24 Korimoto, Kagoshima 890-0065, Japan
| | - Naoki Miura
- Joint Graduate School of Veterinary Medicine, Kagoshima University, 1-21-24 Korimoto, Kagoshima 890-0065, Japan
- Joint Faculty of Veterinary Medicine, Kagoshima University, 1-21-24 Korimoto, Kagoshima 890-0065, Japan
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7
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Ducatel A, Trillaud H, Reizine E, Vilgrain V, Sempoux C, Schmidt-Kobbe S, Gouw ASH, de Haas RJ, Julien C, Paradis V, Blanc JF, Chiche L, Balabaud C, Bioulac-Sage P, Frulio N. Sonic hedgehog hepatocellular adenoma: magnetic resonance imaging features and correlation with histology. Eur Radiol 2024; 34:4649-4662. [PMID: 38012454 DOI: 10.1007/s00330-023-10344-5] [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: 05/08/2023] [Revised: 08/15/2023] [Accepted: 08/21/2023] [Indexed: 11/29/2023]
Abstract
OBJECTIVES Sonic hedgehog hepatocellular adenoma (shHCA) is a new hepatocellular adenoma (HCA) subgroup characterized by high risk of hemorrhage. ShHCA account for below 10% of all HCA cases and are often associated with female gender, obesity, and non-alcoholic steatohepatitis. No specific MRI characteristics have been described to date. The objective of this study was to assess the value of using MRI to identify shHCA, and correlate MRI findings with histology. METHODS We retrospectively collected MRI scans of 29 patients with shHCA from our center and from different liver referral centers to include 35 lesions. Diagnosis of shHCA was assessed by immunohistochemical overexpression of argininosuccinate synthase 1 or prostaglandin D2 synthase, then confirmed by molecular analysis of sonic hedgehog pathway activation and/or by proteomic analysis. RESULTS In 46% (n = 16/35) of shHCA cases, we detected intralesional fluid-filled cavities defined on MR images as fluid-like foci markedly hyperintense on T2-weighted sequences, and hypointense on T1-weighted sequences, with or without delayed enhancement. Pathologically, these cavities were observed in 54% of cases as vacuoles filled with blood at different stages of degradation. Hemorrhage and/or necrosis were detected among 71% of cases by MRI analysis (n = 25/35) versus 82% pathologically. Seventeen percent of shHCA cases (n = 6/35) were completely homogeneous via MRI and pathological analysis. No MRI criteria was found in favor of focal nodular hyperplasia, HNF1A-mutated HCA, or typical inflammatory HCA. CONCLUSION We reveal the presence of intralesional fluid-filled cavities among 46% of our shHCA cases that represent a new MRI finding possibly helpful for shHCA diagnosis. CLINICAL RELEVANCE STATEMENT This multicenter study is the first clinical study about the radiological aspect of this new hepatocellular adenoma subgroup. This highlights a strong correlation between MRI and histological analysis, with a specific pattern emerging for diagnosis. KEY POINTS • Sonic hedgehog hepatocellular adenoma is a new hepatocellular adenoma subgroup associated with high risk of hemorrhage, but imaging features of this subgroup remain unknown. • Analysis of MR images and correlation with pathology revealed intralesional fluid-filled cavities and necrotic-hemorrhagic changes. • Intralesional fluid-filled cavities have not yet been described in other adenoma subtypes and represent a new MRI finding for sonic hedgehog hepatocellular adenoma.
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Affiliation(s)
- Arnaud Ducatel
- Department of Radiology, University Bordeaux Hospital, Hôpital Haut-Lévêque, F-33604, Pessac, France.
| | - Hervé Trillaud
- Department of Radiology, University Bordeaux Hospital, Hôpital Haut-Lévêque, F-33604, Pessac, France
| | - Edouard Reizine
- Department of Radiology, APHP Nord, Hôpital Beaujon, Université Paris Cité, Clichy, France
| | - Valérie Vilgrain
- Department of Radiology, APHP Nord, Hôpital Beaujon, Université Paris Cité, Clichy, France
| | - Christine Sempoux
- Department of Clinical Pathology, Institute of Pathology, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland
| | - Sabine Schmidt-Kobbe
- Department of Diagnostic and Interventional Radiology, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland
| | - Annette S H Gouw
- Department of Pathology and Medical Biology, University Medical Center Groningen, Groningen, The Netherlands
| | - Robbert J de Haas
- Department of Radiology, University Medical Center Groningen, Groningen, The Netherlands
| | - Céline Julien
- Department of Digestive Surgery, University Bordeaux Hospital, Hôpital Haut-Lévêque, F-33604, Pessac, France
| | - Valérie Paradis
- Department of Pathology, APHP, Université de Paris, Hôpital Beaujon, Clichy, France
| | - Jean-Frédéric Blanc
- Department of Hepatogastroenterology and Digestive Oncology, University Bordeaux Hospital, Hôpital Haut-Lévêque, F-33604, Pessac, France
| | - Laurence Chiche
- Department of Digestive Surgery, University Bordeaux Hospital, Hôpital Haut-Lévêque, F-33604, Pessac, France
| | - Charles Balabaud
- UMR 1053, University Bordeaux, INSERM, F-33076, Bordeaux, France
| | | | - Nora Frulio
- Department of Radiology, University Bordeaux Hospital, Hôpital Haut-Lévêque, F-33604, Pessac, France
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8
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Declaux G, Denis de Senneville B, Trillaud H, Bioulac-Sage P, Balabaud C, Blanc JF, Facq L, Frulio N. Assessment of a multivariable model using MRI-radiomics, age and sex for the classification of hepatocellular adenoma subtypes. RESEARCH IN DIAGNOSTIC AND INTERVENTIONAL IMAGING 2024; 10:100046. [PMID: 39077731 PMCID: PMC11265376 DOI: 10.1016/j.redii.2024.100046] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/07/2023] [Accepted: 04/01/2024] [Indexed: 07/31/2024]
Abstract
Objectives Non-invasive subtyping of hepatocellular adenomas (HCA) remains challenging for several subtypes, thus carrying different levels of risks and management. The goal of this study is to devise a multivariable diagnostic model based on basic clinical features (age and sex) combined with MRI-radiomics and to evaluate its diagnostic performance. Methods This single-center retrospective case-control study included all consecutive patients with HCA identified within the pathological database from our institution from January 2003 to April 2018 with MRI examination (T2, T1-no injection/injection-arterial-portal); volumes of interest were manually delineated in adenomas and 38 textural features were extracted (LIFEx, v5.10). Qualitative (i.e., visual on MRI) and automatic (computer-assisted) analysis were compared. The prognostic scores of a multivariable diagnostic model based on basic clinical features (age and sex) combined with MRI-radiomics (tumor volume and texture features) were assessed using a cross-validated Random Forest algorithm. Results Via visual MR-analysis, HCA subgroups could be classified with balanced accuracies of 80.8 % (I-HCA or ß-I-HCA, the two being indistinguishable), 81.8 % (H-HCA) and 74.4 % (sh-HCA or ß-HCA also indistinguishable). Using a model including age, sex, volume and texture variables, HCA subgroups were predicted (multivariate classification) with an averaged balanced accuracy of 58.6 %, best=73.8 % (sh-HCA) and 71.9 % (ß-HCA). I-HCA and ß-I-HCA could be also distinguished (binary classification) with a balanced accuracy of 73 %. Conclusion Multiple HCA subtyping could be improved using machine-learning algorithms including two clinical features, i.e., age and sex, combined with MRI-radiomics. Future HCA studies enrolling more patients will further test the validity of the model.
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Affiliation(s)
- Guillaume Declaux
- Service d'imagerie diagnostique et Interventionnelle, centre médicochirurgical Magellan, hôpital Saint-André, centre hospitalier universitaire de Bordeaux, 33000, Bordeaux, France
| | | | - Hervé Trillaud
- Service d'imagerie diagnostique et Interventionnelle, centre médicochirurgical Magellan, hôpital Saint-André, centre hospitalier universitaire de Bordeaux, 33000, Bordeaux, France
- Université de Bordeaux, CNRS, Inria, Bordeaux INP, IMB, UMR 5251, 33400, Talence, France
| | - Paulette Bioulac-Sage
- Service de pathologie, hôpital Pellegrin, centre hospitalier universitaire de Bordeaux, Bordeaux, France
- Université de Bordeaux, Bordeaux Research in Translational Oncology, Bordeaux, France
| | - Charles Balabaud
- Université de Bordeaux, Bordeaux Research in Translational Oncology, Bordeaux, France
- Service d'hépato-gastroentérologie et oncologie digestive, centre médicochirurgical Magellan, hôpital Haut-Lévêque, centre hospitalier universitaire de Bordeaux, Bordeaux, France
| | - Jean-Frédéric Blanc
- Service d'hépato-gastroentérologie et oncologie digestive, centre médicochirurgical Magellan, hôpital Haut-Lévêque, centre hospitalier universitaire de Bordeaux, Bordeaux, France
| | - Laurent Facq
- Université de Bordeaux, CNRS, Inria, Bordeaux INP, IMB, UMR 5251, 33400, Talence, France
| | - Nora Frulio
- Service d'imagerie diagnostique et Interventionnelle, centre médicochirurgical Magellan, hôpital Saint-André, centre hospitalier universitaire de Bordeaux, 33000, Bordeaux, France
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Kallenbach M, Qvartskhava N, Weigel C, Dörffel Y, Berger J, Kunze G, Luedde T. [Contrast-enhanced ultrasound (CEUS) for characterisation of focal liver lesions]. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:952-970. [PMID: 37798924 PMCID: PMC11211032 DOI: 10.1055/a-2145-7461] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/01/2023] [Accepted: 06/21/2023] [Indexed: 10/07/2023]
Abstract
Due to the trend towards increased use of imaging and rising awareness among high-risk patients, gastroenterologists and hepatologists are more frequently confronted with patients with focal liver lesions. In the differentiation of these lesions, CT and MRI have increasingly found their way into primary diagnostic steps in everyday clinical practice. Contrast-enhanced sonography, on the other hand, is a very effective and cost-efficient method for assessing focal liver lesions. The success of the method is not only based on the visualisation of microvascularisation in real time. If sonography is performed by the treating physician, he can use the exact knowledge of history and clinical findings to specifically adapt the examination procedure and to interpret the sonographic findings with greater accuracy ("clinical sonography"). At the same time, the method enables the practitioner to combine diagnostics and management decisions in his or her own hands. To achieve excellent results with contrast-enhanced sonography-as with any other imaging method-it is necessary that the examiner is sufficiently qualified.This article systematically presents the sonographic characteristics of the most common liver lesions and clearly shows their contrast patterns using videos (available via QR code). The article illustrates that CEUS could-and from the authors' point of view, should-have an even greater significance in the future.
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Affiliation(s)
- Michael Kallenbach
- Department of Gastroenterology Hepatology and Infectious Diseases, University Hospital of Düsseldorf, Düsseldorf, Germany
- Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf (CIO ABCD), Düsseldorf, Germany
| | - Natalia Qvartskhava
- Department of Gastroenterology Hepatology and Infectious Diseases, University Hospital of Düsseldorf, Düsseldorf, Germany
- Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf (CIO ABCD), Düsseldorf, Germany
| | - Christian Weigel
- Department of Gastroenterology Hepatology and Infectious Diseases, University Hospital of Düsseldorf, Düsseldorf, Germany
- Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf (CIO ABCD), Düsseldorf, Germany
| | - Yvonne Dörffel
- Medical Outpatient Department, Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Jens Berger
- Ernst von Bergmann Klinikum, Department of Gastroenterology, Hepatology, Infectious Diseases and Rheumatology, Potsdam, Germany
| | - Georg Kunze
- Schwarzwald-Baar Klinikum Villingen-Schwenningen GmbH, Villingen-Schwenningen, Germany
| | - Tom Luedde
- Department of Gastroenterology Hepatology and Infectious Diseases, University Hospital of Düsseldorf, Düsseldorf, Germany
- Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf (CIO ABCD), Düsseldorf, Germany
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10
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van Rosmalen BV, Visentin M, Furumaya A, van Delden OM, Kazemier G, van Gulik TM, Verheij J, Stieger B. Association Between Gadoxetic Acid-Enhanced Magnetic Resonance Imaging, Organic Anion Transporters, and Farnesoid X Receptor in Benign Focal Liver Lesions. Drug Metab Dispos 2024; 52:118-125. [PMID: 38050024 DOI: 10.1124/dmd.123.001492] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2023] [Revised: 11/21/2023] [Accepted: 11/27/2023] [Indexed: 12/06/2023] Open
Abstract
The organic anion uptake and efflux transporters [organic anion-transporting polypeptide (OATP)1B1, OATP1B3 and multidrug resistance-associated protein (MRP)2 and MRP3] that mediate the transport of the hepatobiliary-specific contrast agent gadoxetate (Gd-EOB-DTPA) are direct or indirect targets of the farnesoid X receptor (FXR), a key regulator of bile acid and lipid homeostasis. In benign liver tumors, FXR expression and activation is not yet characterized. We investigated the expression and activation of FXR and its targets in hepatocellular adenoma (HCA) and focal nodular hyperplasia (FNH) and their correlation with Gd-EOB-DTPA-enhanced magnetic resonance imaging (MRI). Gd-EOB-DTPA MRI patterns were assessed by an expert radiologist. The intensity of the lesions on the hepatobiliary phase was correlated to mRNA expression levels of OATP1B1, OATP1B3, MRP2, MRP3, FXR, and small heterodimer partner (SHP) in fresh surgical specimens of patients with FNH or HCA subtypes. Normal and tumor sample pairs of 43 HCA and 14 FNH were included. All FNH (14/14) were hyperintense. Of the 34 HCA with available Gd-EOB-DTPA-enhanced MRI, 6 were hyperintense and 28 HCA were hypointense. OATP1B3 was downregulated in the hypointense tumors compared with normal surrounding liver tissue (2.77±3.59 vs. 12.9±15.6, P < 0.001). A significant positive correlation between FXR expression and activation and OATP1B3 expression level was found in the HCA cohort. SHP showed a trend toward downregulation in hypointense HCA. In conclusion, this study suggests that the MRI relative signal in HCA may reflect expression level and/or activity of SHP and FXR. Moreover, our data confirms the pivotal role of OATP1B3 in Gd-EOB-DTPA uptake in HCA. SIGNIFICANCE STATEMENT: FXR represents a valuable target for the treatment of liver disease and metabolic syndrome. Currently, two molecules, ursodeoxycholate and obeticholate, are approved for the treatment of primary biliary cirrhosis and cholestasis, with several compounds in clinical trials for the treatment of metabolic dysfunction-associated fatty liver disease. Because FXR expression and activation is associated with gadoxetate accumulation in HCA, an atypical gadoxetate-enhanced MRI pattern might arise in patients under FXR-targeted therapy, thereby complicating the differential diagnosis.
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Affiliation(s)
- Belle V van Rosmalen
- Amsterdam UMC Location University of Amsterdam, Department of Surgery, Amsterdam, The Netherlands (B.V.vR., A.F., T.M.vG.); Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, The Netherlands (B.V.vR., A.F., O.M.vD., T.M.vG., J.V.); Department of Clinical Pharmacology and Toxicology, University Hospital Zurich, Zürich, Switzerland (M.V., B.S.); Amsterdam UMC Location University of Amsterdam, Department of Radiology, Amsterdam, The Netherlands (O.M.vD.); Amsterdam UMC Location Vrije Universiteit Amsterdam, Department of Surgery, Amsterdam, The Netherlands (G.K.); Cancer Center Amsterdam, Amsterdam, The Netherlands (G.K.); and Amsterdam UMC Location University of Amsterdam, Department of Pathology, Amsterdam, The Netherlands (J.V.)
| | - Michele Visentin
- Amsterdam UMC Location University of Amsterdam, Department of Surgery, Amsterdam, The Netherlands (B.V.vR., A.F., T.M.vG.); Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, The Netherlands (B.V.vR., A.F., O.M.vD., T.M.vG., J.V.); Department of Clinical Pharmacology and Toxicology, University Hospital Zurich, Zürich, Switzerland (M.V., B.S.); Amsterdam UMC Location University of Amsterdam, Department of Radiology, Amsterdam, The Netherlands (O.M.vD.); Amsterdam UMC Location Vrije Universiteit Amsterdam, Department of Surgery, Amsterdam, The Netherlands (G.K.); Cancer Center Amsterdam, Amsterdam, The Netherlands (G.K.); and Amsterdam UMC Location University of Amsterdam, Department of Pathology, Amsterdam, The Netherlands (J.V.)
| | - Alicia Furumaya
- Amsterdam UMC Location University of Amsterdam, Department of Surgery, Amsterdam, The Netherlands (B.V.vR., A.F., T.M.vG.); Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, The Netherlands (B.V.vR., A.F., O.M.vD., T.M.vG., J.V.); Department of Clinical Pharmacology and Toxicology, University Hospital Zurich, Zürich, Switzerland (M.V., B.S.); Amsterdam UMC Location University of Amsterdam, Department of Radiology, Amsterdam, The Netherlands (O.M.vD.); Amsterdam UMC Location Vrije Universiteit Amsterdam, Department of Surgery, Amsterdam, The Netherlands (G.K.); Cancer Center Amsterdam, Amsterdam, The Netherlands (G.K.); and Amsterdam UMC Location University of Amsterdam, Department of Pathology, Amsterdam, The Netherlands (J.V.)
| | - Otto M van Delden
- Amsterdam UMC Location University of Amsterdam, Department of Surgery, Amsterdam, The Netherlands (B.V.vR., A.F., T.M.vG.); Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, The Netherlands (B.V.vR., A.F., O.M.vD., T.M.vG., J.V.); Department of Clinical Pharmacology and Toxicology, University Hospital Zurich, Zürich, Switzerland (M.V., B.S.); Amsterdam UMC Location University of Amsterdam, Department of Radiology, Amsterdam, The Netherlands (O.M.vD.); Amsterdam UMC Location Vrije Universiteit Amsterdam, Department of Surgery, Amsterdam, The Netherlands (G.K.); Cancer Center Amsterdam, Amsterdam, The Netherlands (G.K.); and Amsterdam UMC Location University of Amsterdam, Department of Pathology, Amsterdam, The Netherlands (J.V.)
| | - Geert Kazemier
- Amsterdam UMC Location University of Amsterdam, Department of Surgery, Amsterdam, The Netherlands (B.V.vR., A.F., T.M.vG.); Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, The Netherlands (B.V.vR., A.F., O.M.vD., T.M.vG., J.V.); Department of Clinical Pharmacology and Toxicology, University Hospital Zurich, Zürich, Switzerland (M.V., B.S.); Amsterdam UMC Location University of Amsterdam, Department of Radiology, Amsterdam, The Netherlands (O.M.vD.); Amsterdam UMC Location Vrije Universiteit Amsterdam, Department of Surgery, Amsterdam, The Netherlands (G.K.); Cancer Center Amsterdam, Amsterdam, The Netherlands (G.K.); and Amsterdam UMC Location University of Amsterdam, Department of Pathology, Amsterdam, The Netherlands (J.V.)
| | - Thomas M van Gulik
- Amsterdam UMC Location University of Amsterdam, Department of Surgery, Amsterdam, The Netherlands (B.V.vR., A.F., T.M.vG.); Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, The Netherlands (B.V.vR., A.F., O.M.vD., T.M.vG., J.V.); Department of Clinical Pharmacology and Toxicology, University Hospital Zurich, Zürich, Switzerland (M.V., B.S.); Amsterdam UMC Location University of Amsterdam, Department of Radiology, Amsterdam, The Netherlands (O.M.vD.); Amsterdam UMC Location Vrije Universiteit Amsterdam, Department of Surgery, Amsterdam, The Netherlands (G.K.); Cancer Center Amsterdam, Amsterdam, The Netherlands (G.K.); and Amsterdam UMC Location University of Amsterdam, Department of Pathology, Amsterdam, The Netherlands (J.V.)
| | - Joanne Verheij
- Amsterdam UMC Location University of Amsterdam, Department of Surgery, Amsterdam, The Netherlands (B.V.vR., A.F., T.M.vG.); Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, The Netherlands (B.V.vR., A.F., O.M.vD., T.M.vG., J.V.); Department of Clinical Pharmacology and Toxicology, University Hospital Zurich, Zürich, Switzerland (M.V., B.S.); Amsterdam UMC Location University of Amsterdam, Department of Radiology, Amsterdam, The Netherlands (O.M.vD.); Amsterdam UMC Location Vrije Universiteit Amsterdam, Department of Surgery, Amsterdam, The Netherlands (G.K.); Cancer Center Amsterdam, Amsterdam, The Netherlands (G.K.); and Amsterdam UMC Location University of Amsterdam, Department of Pathology, Amsterdam, The Netherlands (J.V.)
| | - Bruno Stieger
- Amsterdam UMC Location University of Amsterdam, Department of Surgery, Amsterdam, The Netherlands (B.V.vR., A.F., T.M.vG.); Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, The Netherlands (B.V.vR., A.F., O.M.vD., T.M.vG., J.V.); Department of Clinical Pharmacology and Toxicology, University Hospital Zurich, Zürich, Switzerland (M.V., B.S.); Amsterdam UMC Location University of Amsterdam, Department of Radiology, Amsterdam, The Netherlands (O.M.vD.); Amsterdam UMC Location Vrije Universiteit Amsterdam, Department of Surgery, Amsterdam, The Netherlands (G.K.); Cancer Center Amsterdam, Amsterdam, The Netherlands (G.K.); and Amsterdam UMC Location University of Amsterdam, Department of Pathology, Amsterdam, The Netherlands (J.V.)
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11
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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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12
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Koek G, Schmitz SM, Bednarsch J, Heise D, Longerich T, Bakers F, Trautwein C, Luedde T, Ulmer TF, Neumann UP. Living-Donor Liver Transplantation for a Large Hepatocellular Carcinoma in a Genetically Identical Twin Sister. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:56-61. [PMID: 38195109 PMCID: PMC10783995 DOI: 10.1055/a-2214-1712] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/31/2023] [Indexed: 01/11/2024]
Abstract
Hepatocellular carcinoma (HCC) is, to date, the most common malignant tumor of the liver and is commonly staged with the Milan criteria. While deceased-donor liver transplantations (DDLT) are reserved for patients within the Milan criteria, living-donor liver transplantation (LDLT) might be a curative option for patients outside the Milan criteria. We here report a case of a 32-year-old woman who developed a giant, unresectable HCC out of a hepatocellular adenoma (HCA) after a pregnancy. The genetically identical twin sister donated her left hemi-liver after ethical approval and preoperative screening. No long-term immunosuppressive therapy was necessary, and after more than eight years, both are in perfect health and the recipient gave birth to a second child. This case shows that in certain situations large HCCs outside the standard criteria can be cured by LT. Careful evaluation of both donor and recipient should be performed for indications like this to assure optimal clinical outcome.
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Affiliation(s)
- Ger Koek
- Department of Internal Medicine, Division of Gastroenterology/Hepatology, Maastricht UMC+, Maastricht, Netherlands
| | - Sophia M. Schmitz
- General-, Visceral and Transplantation Surgery, Universitätsklinikum Essen, Essen, Germany
- General-, Visceral and Transplantation Surgery, University Hospital RWTH Aachen, Aachen, Germany
| | - Jan Bednarsch
- General-, Visceral and Transplantation Surgery, Universitätsklinikum Essen, Essen, Germany
- General-, Visceral and Transplantation Surgery, University Hospital RWTH Aachen, Aachen, Germany
| | - Daniel Heise
- General-, Visceral and Transplantation Surgery, Universitätsklinikum Essen, Essen, Germany
- General-, Visceral and Transplantation Surgery, University Hospital RWTH Aachen, Aachen, Germany
| | - Thomas Longerich
- Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany
| | - Frank Bakers
- Department of Radiology, Maastricht UMC+, Maastricht, Netherlands
| | - Christian Trautwein
- Department of Gastroenterology Metabolic Disorders and Internal Intensive Medicine, University Hospital RWTH Aachen, Aachen, Germany
| | - Tom Luedde
- Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Duesseldorf, Duesseldorf, Germany
| | - Tom Florian Ulmer
- General-, Visceral and Transplantation Surgery, Universitätsklinikum Essen, Essen, Germany
- General-, Visceral and Transplantation Surgery, University Hospital RWTH Aachen, Aachen, Germany
- Department of Surgery, Maastricht UMC+, Maastricht, Netherlands
| | - Ulf Peter Neumann
- General-, Visceral and Transplantation Surgery, Universitätsklinikum Essen, Essen, Germany
- General-, Visceral and Transplantation Surgery, University Hospital RWTH Aachen, Aachen, Germany
- Department of Surgery, Maastricht UMC+, Maastricht, Netherlands
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13
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Ushio N, Hasan MN, Arif M, Miura N. Novel Y RNA-Derived Fragments Can Differentiate Canine Hepatocellular Carcinoma from Hepatocellular Adenoma. Animals (Basel) 2023; 13:3054. [PMID: 37835660 PMCID: PMC10571523 DOI: 10.3390/ani13193054] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2023] [Revised: 09/16/2023] [Accepted: 09/27/2023] [Indexed: 10/15/2023] Open
Abstract
Hepatocellular carcinomas (HCC) are common tumors, whereas hepatocellular adenomas (HCA) are rare, benign tumors in dogs. The aberrant expression of noncoding RNAs (ncRNAs) plays a pivotal role in HCC tumorigenesis and progression. Among ncRNAs, micro RNAs have been widely researched in human HCC, but much less widely in canine HCC. However, Y RNA-derived fragments have yet to be investigated in canine HCC and HCA. This study targeted canine HCC and HCA patients. We used qRT-PCR to determine Y RNA expression in clinical tissues, plasma, and plasma extracellular vesicles, and two HCC cell lines (95-1044 and AZACH). Y RNA was significantly decreased in tissue, plasma, and plasma extracellular vesicles for canine HCC versus canine HCA and healthy controls. Y RNA was decreased in 95-1044 and AZACH cells versus normal liver tissue and in AZACH versus 95-1044 cells. In plasma samples, Y RNA levels were decreased in HCC versus HCA and Healthy controls and increased in HCA versus Healthy controls. Receiver operating characteristic analysis showed that Y RNA could be a promising biomarker for distinguishing HCC from HCA and healthy controls. Overall, the dysregulated expression of Y RNA can distinguish canine HCC from HCA. However, further research is necessary to elucidate the underlying Y RNA-related molecular mechanisms in hepatocellular neoplastic diseases. To the best of our knowledge, this is the first report on the relative expression of Y RNA in canine HCC and HCA.
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Affiliation(s)
- Norio Ushio
- United Graduate School of Veterinary Science, Yamaguchi University, 1677-1 Yoshida, Yamaguchi 753-0841, Japan;
| | - Md Nazmul Hasan
- Joint Graduate School of Veterinary Medicine, Kagoshima University, 1-21-24 Korimoto, Kagoshima 890-0065, Japan; (M.N.H.); (M.A.)
| | - Mohammad Arif
- Joint Graduate School of Veterinary Medicine, Kagoshima University, 1-21-24 Korimoto, Kagoshima 890-0065, Japan; (M.N.H.); (M.A.)
| | - Naoki Miura
- United Graduate School of Veterinary Science, Yamaguchi University, 1677-1 Yoshida, Yamaguchi 753-0841, Japan;
- Joint Graduate School of Veterinary Medicine, Kagoshima University, 1-21-24 Korimoto, Kagoshima 890-0065, Japan; (M.N.H.); (M.A.)
- Clinical Veterinary Division, Faculty of Veterinary Medicine, Airlangga University, Mulyorejo, Surabaya 60115, Indonesia
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14
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Umetsu SE, Kakar S. Evaluating Liver Biopsies with Well-Differentiated Hepatocellular Lesions. Surg Pathol Clin 2023; 16:581-598. [PMID: 37536890 DOI: 10.1016/j.path.2023.04.011] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/05/2023]
Abstract
Needle core biopsies of liver lesions can be challenging, particularly in cases with limited material. The differential diagnosis for well-differentiated hepatocellular lesions includes focal nodular hyperplasia, hepatocellular adenoma, and well-differentiated hepatocellular carcinoma (HCC) in noncirrhotic liver, while dysplastic nodules and well-differentiated HCC are the primary considerations in cirrhotic liver. The first part of this review focuses on histochemical and immunohistochemical stains as well as molecular assays that are useful in the differential diagnosis. The second portion describes the features of hepatocellular adenoma subtypes and focuses on the differential diagnoses in commonly encountered clinicopathologic scenarios.
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Affiliation(s)
- Sarah E Umetsu
- Department of Pathology, University of California San Francisco, 505 Parnassus Avenue, Box 0102, San Francisco, CA 94143, USA.
| | - Sanjay Kakar
- Department of Pathology, University of California San Francisco, 505 Parnassus Avenue, Box 0102, San Francisco, CA 94143, USA
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15
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González IA, Torbenson M, Sharifai N, Byrnes K, Chatterjee D, Kakar S, Yeh MM, Wu TT, Zhang X, Jain D. Clinicopathologic characterization of hepatocellular adenomas in men: a multicenter experience. Hum Pathol 2023; 138:24-33. [PMID: 37245629 DOI: 10.1016/j.humpath.2023.05.010] [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: 04/13/2023] [Revised: 05/18/2023] [Accepted: 05/22/2023] [Indexed: 05/30/2023]
Abstract
Hepatocellular adenomas (HCAs) are benign liver neoplasms which most commonly present in women in their reproductive age. In men, they are rare and have a higher risk of malignant transformation to hepatocellular carcinoma (HCC). Here we present our multicenter experience with HCA in men in the United States. A total of 27 HCA cases were included, with a mean age of presentation of 37 years (range, 9-69 years) and a mean size of 6.8 cm (range, 0.9-18.5 cm). Based on the 2019 World Health Organization classification, the most common subtype identified was inflammatory HCA (IHCA; 10 cases, 37.0%) followed by unclassified HCA (UHCA; 7 cases, 25.9%), HNF1A-inactivated HCA (H-HCA; 6 cases, 22.2%), β-catenin-activated IHCA (b-IHCA; 3 cases, 11.1%), and β-catenin-activated HCA (b-HCA; 1 case, 3.7%). Six additional cases diagnosed as hepatocellular neoplasm of uncertain malignant potential (HUMP) were also included in the study. These cases presented in a mean age of 46 years (range, 17-64 years) and a size of 10.8 cm (range, 4.2-16.5 cm). We evaluated the significance of androgen receptor (AR) expression by immunohistochemistry (IHC); of the 16 cases with materials available, 8 were considered positive using the Allred score system (2 IHCA, 2 H-HCA, 1 UHCA, and 3 HUMP). Of the total cases, 12 were diagnosed on biopsies, for which follow-up information is available for 7, and none of them show evidence of malignant transformation. Of the 21 resection cases, a concomitant well-differentiated HCC within the same lesion was identified in 5 cases (23.8%), which were diagnosed as HCA (n = 4) or HUMP (n = 1). Overall, 15% of cases in our entire cohort of HCA and HUMP showed concomitant HCC, while none of the 7 biopsy cases showed any malignant transformation on follow-up (range, 22-160 months; mean, 61.8 months).
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Affiliation(s)
- Iván A González
- Department of Pathology, Yale University, New Haven, CT, 06520, USA
| | - Michael Torbenson
- Division of Anatomic Pathology, Mayo Clinic, Rochester, MN, 55901, USA
| | - Nima Sharifai
- Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO, 63110, USA
| | - Kathleen Byrnes
- Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO, 63110, USA
| | - Deyali Chatterjee
- Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO, 63110, USA
| | - Sanjay Kakar
- Department of Pathology, University of California, San Francisco, San Francisco, CA, 94143, USA
| | - Matthew M Yeh
- Department of Laboratory Medicine and Pathology, University of Washington School of Medicine, Seattle, WA, 98195, USA
| | - Tsung-Teh Wu
- Division of Anatomic Pathology, Mayo Clinic, Rochester, MN, 55901, USA
| | - Xuchen Zhang
- Department of Pathology, Yale University, New Haven, CT, 06520, USA
| | - Dhanpat Jain
- Department of Pathology, Yale University, New Haven, CT, 06520, USA.
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16
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Jiao J, Finberg KE, Jain D, Morotti R. Hepatocellular Adenoma: Report of 2 Cases That Highlight the Relevance of Phenotype-Genotype Correlation in the Pediatric Population. Pediatr Dev Pathol 2023; 26:394-403. [PMID: 37334553 DOI: 10.1177/10935266231175426] [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] [Indexed: 06/20/2023]
Abstract
BACKGROUND Hepatocellular adenoma (HCA) in the pediatric population is very rare and there are only limited studies, especially with molecular characterization of the tumors. Main HCA subtypes recognized in the current WHO classification include HNF1A-inactivated HCA (H-HCA), inflammatory HCA (IHCA), β-catenin-activated HCA (b-HCA), and β-catenin-activated IHCA (b-IHCA) and sonic hedgehog HCA (shHCA) is reported as an emerging subtype. METHODS Clinical history, pathological information, and molecular studies for a series of 2 cases of pediatric HCA were reviewed. RESULTS Case 1 was a b-HCA characterized by somatic CTNNB1 S45 mutation in a 11-year-old male with Abernethy malformation. Case 2 was a H-HCA characterized by germline HNF1A variant (c.526+1G>A) in a 15-year-old male associated with maturity-onset diabetes of the young type 3 (MODY3). CONCLUSION Our findings highlight the rarity of these 2 cases associated with adenomatosis, and the contribution of molecular/genetic analysis for proper sub-typing, prognosis and family surveillance.
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Affiliation(s)
- Jingjing Jiao
- Department of Pathology, Yale School of Medicine, New Haven, CT, USA
| | - Karin E Finberg
- Department of Pathology, Yale School of Medicine, New Haven, CT, USA
| | - Dhanpat Jain
- Department of Pathology, Yale School of Medicine, New Haven, CT, USA
| | - Raffaella Morotti
- Department of Pathology, Yale School of Medicine, New Haven, CT, USA
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17
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Cekuolis A, Schreiber-Dietrich D, Augustinienė R, Taut H, Squires J, Chaves EL, Dong Y, Dietrich CF. Incidental Findings in Pediatric Patients: How to Manage Liver Incidentaloma in Pediatric Patients. Cancers (Basel) 2023; 15:2360. [PMID: 37190288 PMCID: PMC10137002 DOI: 10.3390/cancers15082360] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2023] [Revised: 04/11/2023] [Accepted: 04/12/2023] [Indexed: 05/17/2023] Open
Abstract
The World Federation for Ultrasound in Medicine and Biology (WFUMB) is addressing the issue of incidental findings (IFs) with a series of publications entitled "Incidental imaging findings-the role of ultrasound". IFs in the liver of newborns and children are rare and much less commonly encountered than in adults; as a result, they are relatively much more frequently malignant and life-threatening, even when they are of benign histology. Conventional B-mode ultrasound is the well-established first line imaging modality for the assessment of liver pathology in pediatric patients. US technological advances, resulting in image quality improvement, contrast-enhanced ultrasound (CEUS), liver elastography and quantification tools for steatosis have expanded the use of ultrasound technology in daily practice. The following overview is intended to illustrate incidentally detected liver pathology covering all pediatric ages. It aims to aid the examiner in establishing the final diagnosis. Management of incidentally detected focal liver lesions (FLL) needs to take into account the diagnostic accuracy of each imaging modality, the patient's safety issues (including ionizing radiation and nephrotoxic contrast agents), the delay in diagnosis, the psychological burden on the patient and the cost for the healthcare system. Moreover, this paper should help the pediatric clinician and ultrasound practitioner to decide which pathologies need no further investigation, which ones require interval imaging and which cases require further and immediate diagnostic procedures.
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Affiliation(s)
- Andrius Cekuolis
- Ultrasound Section, Department of Pediatric Radiology, Radiology and Nuclear Medicine Centre, Vilnius University Hospital Santaros Klinikos, 08661 Vilnius, Lithuania
| | | | - Rasa Augustinienė
- Ultrasound Section, Department of Pediatric Radiology, Radiology and Nuclear Medicine Centre, Vilnius University Hospital Santaros Klinikos, 08661 Vilnius, Lithuania
| | - Heike Taut
- Children’s Hospital, Universitätsklinikum Dresden, Technische Universität Dresden, 01062 Dresden, Germany
| | - Judy Squires
- Department of Radiology, UPMC Children’s Hospital of Pittsburgh, Pittsburgh, PA 15224, USA
| | - Edda L. Chaves
- Radiology Department, Hospital Regional Nicolas Solano, La Chorrera 1007, Panama
| | - Yi Dong
- Department of Ultrasound, Xinhua Hospital affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200092, China
| | - Christoph F. Dietrich
- Department Allgemeine Innere Medizin (DAIM), Kliniken Hirslanden Beau Site, Salem und Permancence, 3013 Bern, Switzerland
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18
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Kusnik A, Li S, Graziano E, Katerji R, Ramaraju G. A Case of a Beta-Catenin-Activated Hepatic Adenoma in a Male Patient With Familial Adenomatous Polyposis. ACG Case Rep J 2023; 10:e01012. [PMID: 36936132 PMCID: PMC10019209 DOI: 10.14309/crj.0000000000001012] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2022] [Revised: 01/31/2023] [Accepted: 02/13/2023] [Indexed: 03/17/2023] Open
Abstract
Hepatocellular adenoma is a benign liver tumor often diagnosed incidentally in women of reproductive age who are taking oral contraceptives. In this study, we present a unique case of an 18-year-old man with known familial adenomatous polyposis who presented with sepsis in the setting of a recent total proctocolectomy and was incidentally found to have multiple large hepatic lesions. A biopsy of a liver lesion confirmed the diagnosis of a beta-catenin-activated hepatic adenoma. To the best of our knowledge, this is the first known case of beta-catenin-activated hepatic adenoma in a patient with a known familial adenomatous polyposis mutation. Beta-catenin is one of the many subtypes of hepatocellular adenomas, which carries a high risk of malignant transformation.
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Affiliation(s)
| | - Shifan Li
- Department of Internal Medicine, University of Rochester Medical Center, Rochester, NY
| | - Elliot Graziano
- Division of Gastroenterology and Hepatology, University of Rochester Medical Center, Rochester, NY
| | - Roula Katerji
- Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY
| | - Gopal Ramaraju
- Division of Gastroenterology and Hepatology, University of Rochester Medical Center, Rochester, NY
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19
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Demory A, Péron JM, Calderaro J, Selves J, Mokrane FZ, Amaddeo G, Paradis V, Ziol M, Sutter O, Blaise L, Ganne-Carrié N, Vilgrain V, Cauchy F, Zucman-Rossi J, Ronot M, Nault JC. Body weight changes and duration of estrogen exposure modulate the evolution of hepatocellular adenomas after contraception discontinuation. Hepatology 2023; 77:430-442. [PMID: 35980227 DOI: 10.1002/hep.32734] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/01/2022] [Revised: 07/28/2022] [Accepted: 08/05/2022] [Indexed: 01/28/2023]
Abstract
BACKGROUND AND AIMS The natural history of hepatocellular adenomas (HCAs) remains to be better described, especially in nonresected patients. We aim to identify the predictive factors of HCA evolution after estrogen-based contraception discontinuation. APPROACH AND RESULTS We retrospectively included patients with a histological diagnosis of HCA from three centers. Clinical, radiological, and pathological data were collected to identify predictive factors of radiological evolution per Response Evaluation Criteria in Solid Tumors, version 1.1, and occurrence of complications (bleeding, malignant transformation). We built a score using variables that modulate estrogen levels: body mass index and duration of estrogen-based contraception. An external cohort was used to validate this score. 183 patients were included in the cohort, including 161 women (89%) using estrogen-based contraception for a median of 12 years. Thirty percent of patients had at least one HNF1A -inactivated HCA, 45.5% at least one inflammatory HCA, and 11% at least one HCA with activation of β-catenin (bHCA). Twenty-one symptomatic bleedings (11%) and eleven malignant transformations (6%) occurred. Ages < 37 years old ( p = 0.004) and HCA > 5 cm at imaging were independently associated with symptomatic bleeding ( p = 0.003), whereas a bHCA was associated with malignant transformation ( p < 0.001). After a median follow-up of 5 years, radiological regression was observed in 31%, stabilization in 47%, and progression in 22% of patients. Weight loss was associated with regression ( p < 0.0001) and weight gain with progression ( p = 0.02). The estrogen exposure score predicted radiological regression (odds ratio, 2.33; confidence interval 95%, 1.29-4.19; p = 0.005) with a linear relationship between the rate of estrogen exposure and the probability of regression. This result was confirmed in an external cohort of 72 female patients ( p = 0.003). CONCLUSION Weight variation is strongly associated with radiological evolution after oral contraception discontinuation. A score of estrogen exposure, easily assessable in clinical practice at diagnosis, predicts regression of HCA.
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Affiliation(s)
- Alix Demory
- Service d'hépatologie , Hôpital Avicenne , Hôpitaux Universitaires Paris-Seine-Saint-Denis , Assistance-Publique-Hôpitaux de Paris , Bobigny , France.,Unité de Formation et de Recherche Santé Médecine et Biologie Humaine , Université Paris Nord , Paris , France.,Centre de Recherche des Cordeliers , Inserm, Sorbonne Université, Université Paris, INSERM, Functional Genomics of Solid Tumors laboratory , Paris , France
| | - Jean-Marie Péron
- Service d'hépatogastroentérologie , hôpital Rangueil , CHU Toulouse Assistance , Toulouse , France
| | - Julien Calderaro
- Department of Pathology , Publique-Hôpitaux de Paris , Henri Mondor-Albert Chenevier University Hospital , Créteil , France.,Université Paris Est Créteil , INSERM, IMRB , Créteil , France.,INSERM, Unit U955, Team 18 , Créteil , France
| | - Janick Selves
- Service d'anatomopathologie , hôpital Rangueil , CHU Toulouse Assistance , Toulouse , France
| | - Fatima-Zohra Mokrane
- Service de radiologie , hôpital Rangueil , CHU Toulouse Assistance , Toulouse , France
| | - Giuliana Amaddeo
- Assistance Publique-Hôpitaux de Paris , Hôpital Henri Mondor, Service d'Hépatologie , Créteil , France.,Université Paris Est Créteil, INSERM, IMRB , Créteil , France.,INSERM, U955, Equipe 18 "Physiopathologie et Thérapeutiques des Hépatites Virales Chroniques et des cancers liés" , Créteil , France
| | - Valérie Paradis
- Assistance Publique-Hôpitaux de Paris , Hôpital Beaujon, Service d'anatomopathologie , Clichy , France.,Université de Paris Cité, Centre de recherche sur l'inflammation, Inserm, U1149, CNRS, ERL8252 , Paris , France
| | - Marianne Ziol
- Unité de Formation et de Recherche Santé Médecine et Biologie Humaine , Université Paris Nord , Paris , France.,Centre de Recherche des Cordeliers , Inserm, Sorbonne Université, Université Paris, INSERM, Functional Genomics of Solid Tumors laboratory , Paris , France.,Service d'anatomopathologie , Hôpital Avicenne, Hôpitaux Universitaires Paris-Seine-Saint-Denis, Assistance-Publique-Hôpitaux de Paris , Bobigny , France
| | - Olivier Sutter
- Service de radiologie , Hôpitaux Universitaires Paris-Seine-Saint-Denis, Assistance-Publique-Hôpitaux de Paris , Bobigny , France
| | - Lorraine Blaise
- Service d'hépatologie , Hôpital Avicenne , Hôpitaux Universitaires Paris-Seine-Saint-Denis , Assistance-Publique-Hôpitaux de Paris , Bobigny , France
| | - Nathalie Ganne-Carrié
- Service d'hépatologie , Hôpital Avicenne , Hôpitaux Universitaires Paris-Seine-Saint-Denis , Assistance-Publique-Hôpitaux de Paris , Bobigny , France.,Unité de Formation et de Recherche Santé Médecine et Biologie Humaine , Université Paris Nord , Paris , France.,Centre de Recherche des Cordeliers , Inserm, Sorbonne Université, Université Paris, INSERM, Functional Genomics of Solid Tumors laboratory , Paris , France
| | - Valérie Vilgrain
- Assistance Publique-Hôpitaux de Paris , Hôpital Beaujon, Service de radiologie , Clichy , France.,INSERM U1149 "Centre de Recherche Sur L'inflammation" , CRI, Université Paris Cité , Paris , France
| | - François Cauchy
- INSERM U1149 "Centre de Recherche Sur L'inflammation" , CRI, Université Paris Cité , Paris , France.,Assistance Publique-Hôpitaux de Paris , Hôpital Beaujon, Service de chirurgie hépato-biliaire , Clichy , France
| | - Jessica Zucman-Rossi
- Centre de Recherche des Cordeliers , Inserm, Sorbonne Université, Université Paris, INSERM, Functional Genomics of Solid Tumors laboratory , Paris , France.,Assistance Publique-Hôpitaux de Paris , Service d'Oncologie Médicale, Hôpital Européen Georges Pompidou , Paris , France
| | - Maxime Ronot
- Assistance Publique-Hôpitaux de Paris , Hôpital Beaujon, Service de radiologie , Clichy , France.,INSERM U1149 "Centre de Recherche Sur L'inflammation" , CRI, Université Paris Cité , Paris , France
| | - Jean-Charles Nault
- Service d'hépatologie , Hôpital Avicenne , Hôpitaux Universitaires Paris-Seine-Saint-Denis , Assistance-Publique-Hôpitaux de Paris , Bobigny , France.,Unité de Formation et de Recherche Santé Médecine et Biologie Humaine , Université Paris Nord , Paris , France.,Centre de Recherche des Cordeliers , Inserm, Sorbonne Université, Université Paris, INSERM, Functional Genomics of Solid Tumors laboratory , Paris , France
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20
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Schaible J, Schreyer AG, Mehrabi A, Longerich T, Kieser M, Kreimeyer S, Klauss M, Grenacher L. Subtyping of hepatocellular adenomas using Gd-EOB-DTPA: a qualitative and quantitative analysis. Acta Radiol 2023:2841851221149197. [PMID: 36650712 DOI: 10.1177/02841851221149197] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
BACKGROUND The goal of medical imaging is not only to identify the entity "hepatocellular adenoma," but to detect typical magnetic resonance (MR) patterns of the subtypes so that lesions with a higher malignant transformation rate could be differentiated from those that should just be controlled. PURPOSE To evaluate the differentiation between subtypes of hepatocellular adenomas using hepatobiliary specific contrast agent (Gd-EOB-DTPA) in MR imaging. MATERIAL/METHODS A total of 11 patients with 39 lesions with histologically proven hepatocellular adenomas were evaluated. Of the, 34 were inflammatory hepatocellular adenomas (IHCA) and 5 were HNF1α adenomas. No β-catenin-mutated adenoma was found. In all patients, a standard protocol considering the guidelines of the international consensus conference of Gd-EOB-DTPA was performed in a 1.5-T scanner. Besides a qualitative analysis of all sequences, we measured the quantitative signal intensity (SI) ratio in all examinations. RESULTS Qualitative analysis showed that best sequences for differentiation of HNF1α adenomas from IHCA were T1-weighted (T1W) precontrast (P = 0.03) and portalvenous phase (P < 0.0001) as well as arterial phase (P = 0.002). All adenomas were hypointense in hepatobiliary phase (15 min). The quantitative analyses of the SI ratio and of lesion-to-liver contrast (LLC) ratio show statistically significant differences in T1W precontrast (SI: P = 0.035; LLC: P = 0.049) and portalvenous phase (SI: P = 0.002; LLC: P = 0.002). CONCLUSION Subtyping of hepatocellular adenomas using Gd-EOB-DTPA is possible due to qualitative and quantitative analyses regarding T1W precontrast and portalvenous phase. In addition, the SI ratio and liver-to-lesion contrast ratio in the arterial phase gave additional qualitative information for differentiation.
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Affiliation(s)
- Jan Schaible
- Conradia, Diagnostic Imaging and Prevention Center, Munich, Germany
| | - Andreas G Schreyer
- Department of Radiology, University Medical Center Brandenburg an der Havel, Brandenburg, Germany
| | - Arianeb Mehrabi
- Department of Visceral Surgery, University of Heidelberg, Heidelberg, Germany
| | - Thomas Longerich
- Institute of Pathology, University of Heidelberg, Heidelberg, Germany
| | - Meinhard Kieser
- Institute of Medical Biometry and Informatics, University of Heidelberg, Heidelberg, Germany
| | - Sylvia Kreimeyer
- Diagnostic and Interventional Radiology, University of Heidelberg, Heidelberg, Germany
| | - Miriam Klauss
- Diagnostic and Interventional Radiology, University of Heidelberg, Heidelberg, Germany
| | - Lars Grenacher
- Conradia, Diagnostic Imaging and Prevention Center, Munich, Germany.,Diagnostic and Interventional Radiology, University of Heidelberg, Heidelberg, Germany
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21
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Kim TH, Woo S, Ebrahimzadeh S, McInnes MDF, Gerst SR, Do RK. Hepatic Adenoma Subtypes on Hepatobiliary Phase of Gadoxetic Acid-Enhanced MRI: Systematic Review and Meta-Analysis. AJR Am J Roentgenol 2023; 220:28-38. [PMID: 35920706 PMCID: PMC11759479 DOI: 10.2214/ajr.22.27989] [Citation(s) in RCA: 20] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
BACKGROUND. Accumulating evidence indicates that hepatocellular adenoma (HCA) may have a higher frequency of hepatobiliary phase (HBP) iso- or hyperintensity than previously reported. OBJECTIVE. The purpose of this study was to evaluate the proportion of HCA that shows iso- or hyperintensity in the HBP of gadoxetic acid-enhanced MRI, stratified by HCA subtype (HNF1a-inactivated [H-HCA], inflammatory [I-HCA], β-catenin-activated [B-HCA], and unclassified [U-HCA] HCA), and to assess the diagnostic performance of HBP iso- or hyperintensity for differentiating focal nodular hyperplasia (FNH) from HCA. EVIDENCE ACQUISITION. PubMed, Embase, and Cochrane Central Register of Controlled Trials were searched through February 14, 2022, for articles reporting HBP signal intensity on gadoxetic acid-enhanced MRI among pathologically proven HCAs, stratified by subtype. The pooled proportion of HBP iso- or hyperintensity was determined for each subtype and compared using metaregression. Diagnostic performance of HBP iso- or hyperintensity for differentiating FNH from all HCA subtypes combined and from B-HCA and U-HCA combined was assessed using bivariate modeling. EVIDENCE SYNTHESIS. Twenty-eight studies (12 original investigations, 16 case reports or case series) were included, yielding 364 patients with 410 HCAs (112 H-HCAs, 203 I-HCAs, 33 B-HCAs, 62 U-HCAs). Pooled proportion of HBP iso- or hyperintensity was 14% (95% CI, 4-26%) among all HCAs, 0% (95% CI, 0-2%) among H-HCAs, 11% (95% CI, 0-29%) among U-HCAs, 14% (95% CI, 2-31%) among I-HCAs, and 59% (95% CI, 26-88%) among B-HCAs; metaregression showed significant difference among subtypes (p < .001). In four studies reporting diagnostic performance information, HBP iso- or hyperintensity had sensitivity of 99% (95% CI, 57-100%) and specificity of 89% (95% CI, 82-94%) for differentiating FNH from all HCA subtypes and sensitivity of 99% (95% CI, 53-100%) and specificity of 65% (95% CI, 44-80%) for differentiating FNH from B-HCA or U-HCA. CONCLUSION. HCA subtypes other than H-HCA show proportions of HBP iso- or hyperintensity ranging from 11% (U-HCA) to 59% (B-HCA). Low prevalence of B-HCA has contributed to prior reports of high diagnostic performance of HBP iso- or hyperintensity for differentiating FNH from HCA. CLINICAL IMPACT. Radiologists should recognize the low specificity of HBP iso- or hyperintensity on gadoxetic acid-enhanced MRI for differentiating FNH from certain HCA subtypes.
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Affiliation(s)
- Tae-Hyung Kim
- Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY 10065
| | - Sungmin Woo
- Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY 10065
| | - Sanam Ebrahimzadeh
- Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada
| | - Matthew D F McInnes
- Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada
- Department of Radiology, Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada
| | - Scott R Gerst
- Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY 10065
| | - Richard K Do
- Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY 10065
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22
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González IA, Surrey LF, Russo P. Hepatocellular Adenoma in an Infant With Burn-McKeown Syndrome: Report of a Case. Pediatr Dev Pathol 2022; 25:668-671. [PMID: 36262073 DOI: 10.1177/10935266221109468] [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] [Indexed: 12/14/2022]
Abstract
Hepatocellular adenomas (HCA) in infants are exceedingly rare with only 5 cases reported to the best of our knowledge, all of them preceding the classification of HCA. Here we present an autopsy case of a 9-month-old girl with Burn-McKeown syndrome with an incidental liver nodule in the right lobe measuring 1.5 cm in greatest dimension. The lesion was composed of an unencapsulated proliferation of hepatocytes with multiple unaccompanied arteries without well-formed portal tracts, and an intact reticulin framework without thickened hepatic plates, findings consistent with an HCA. Glutamine synthetase (GS), lipid fatty acid-binding protein (LFABP), c-reactive protein (CRP), serum amyloid-a (SAA), beta-catenin and CD34 immunostains were performed. GS was diffusely and strongly positive in the lesion, CD34 showed heterogenous staining of sinusoids within the lesion without a well-formed rim from the background liver and beta-catenin was negative for nuclear staining. CRP and SAA were considered negative, and LFABP was retained. Molecular testing showed no CTNNB1 variants and found two tier 3 variants involving CHEK2 and PTEN genes. These findings are consistent with an unclassified HCA (U-HCA) per the 2019 WHO Classification of Tumors, representing the youngest patient reported. This raises the possibility that some HCAs are congenital or develop very early in life, remaining undiagnosed until later in life.
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Affiliation(s)
- Iván A González
- Department of Pathology and Laboratory Medicine, 6567Children's Hospital of Philadelphia, Philadelphia, PA, USA
| | - Lea F Surrey
- Department of Pathology and Laboratory Medicine, 6567Children's Hospital of Philadelphia, Philadelphia, PA, USA
| | - Pierre Russo
- Department of Pathology and Laboratory Medicine, 6567Children's Hospital of Philadelphia, Philadelphia, PA, USA
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23
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Nault JC, Paradis V, Ronot M, Zucman-Rossi J. Benign liver tumours: understanding molecular physiology to adapt clinical management. Nat Rev Gastroenterol Hepatol 2022; 19:703-716. [PMID: 35835851 DOI: 10.1038/s41575-022-00643-5] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/01/2022] [Indexed: 12/08/2022]
Abstract
Improvements in understanding the pathophysiology of the different benign liver nodules have refined their nosological classification. New criteria have been identified using imaging, histology and molecular analyses for a precise diagnosis of these tumours. Improvement in the classification of liver tumours provides a more accurate prediction of disease progression and has modified patient management. Haemangioma and focal nodular hyperplasia, the most common benign liver tumours that develop in the absence of chronic liver disease, are usually easy to diagnose on imaging and do not require specific treatment. However, hepatocellular adenomas and cirrhotic macronodules can be difficult to discriminate from hepatocellular carcinoma. The molecular subtyping of hepatocellular adenomas in five major subgroups defined by HNF1A inactivation, β-catenin mutation in exon 3 or exon 7/8, and activation of inflammatory or Hedgehog pathways helps to identify the tumours at risk of malignant transformation or bleeding. New clinical, biological and molecular tools have gradually been included in diagnostic and treatment algorithms to classify benign liver tumours and improve patient management. This Review aims to explain the main pathogenic mechanisms of benign liver tumours and how this knowledge could influence clinical practice.
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Affiliation(s)
- Jean-Charles Nault
- Service d'hépatologie, Hôpital Avicenne, Hôpitaux Universitaires Paris-Seine-Saint-Denis, Assistance-Publique Hôpitaux de Paris, Bobigny, France. .,Unité de Formation et de Recherche Santé Médecine et Biologie Humaine, Université Paris Nord, Communauté d'Universités et Etablissements Sorbonne Paris Cité, Paris, France. .,Centre de Recherche des Cordeliers, Sorbonne Université, Inserm, Université de Paris Cité, team «Functional Genomics of Solid Tumors», Paris, France. .,Equipe labellisée Ligue Nationale Contre le Cancer, Labex OncoImmunology, Paris, France.
| | - Valérie Paradis
- Service de Pathologie, Hôpital Beaujon, AP-HP Nord, Clichy, France.,Université de Paris, INSERM U1149 "Centre de Recherche sur l'inflammation", CRI, Paris, France
| | - Maxime Ronot
- Université de Paris, INSERM U1149 "Centre de Recherche sur l'inflammation", CRI, Paris, France.,Department of Radiology, Assistance-Publique Hôpitaux de Paris, Hôpital Beaujon, AP-HP Nord, Clichy, France
| | - Jessica Zucman-Rossi
- Centre de Recherche des Cordeliers, Sorbonne Université, Inserm, Université de Paris Cité, team «Functional Genomics of Solid Tumors», Paris, France. .,Equipe labellisée Ligue Nationale Contre le Cancer, Labex OncoImmunology, Paris, France. .,Hôpital Européen Georges Pompidou, APHP, Paris, France.
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24
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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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25
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Luo L, Wang T, Cheng M, Ge X, Song S, Zhu G, Xiao Y, Deng W, Xie J, Shan R. Rare benign liver tumors that require differentiation from hepatocellular carcinoma: focus on diagnosis and treatment. J Cancer Res Clin Oncol 2022:10.1007/s00432-022-04169-w. [PMID: 35789428 DOI: 10.1007/s00432-022-04169-w] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2022] [Accepted: 06/21/2022] [Indexed: 11/24/2022]
Abstract
BACKGROUND/AIM Recently, an increase in the number of asymptomatic rare benign liver tumors (BLTs) has been reported during health check-ups. It is difficult to determine the nature of partial rare BLTs and not easy to distinguish from malignant liver tumors. This study aimed to analysis clinical features, diagnosis and treatment of rare BLTs to reduce misdiagnosis and provide reference for clinical practice. METHODS From January 2012 to January 2021, we treated 112 rare BLTs by hepatectomy, including 54 focal nodular hyperplasias, 14 hepatocellular adenomas, 28 hepatic angiomyolipomas, 3 hepatic granulomas, 2 inflammatory pseudotumors of the liver, 2 nodular regenerative hyperplasia, 2 hepatic lipomas, 1 solitary fibrous tumor of the liver, 1 hepatic schwannoma and 1 hepatic myelolipoma. RESULTS The majority of patients were middle-aged female and asymptomatic. Single tumors were dominant. The diagnostic accuracies of computed tomography (CT) and magnetic resonance imaging (MRI) were 32.5% and 44.2%, respectively. The majority of tumors were likely to be misdiagnosed as hepatocellular carcinoma (HCC) or difficult to distinguish from HCC. All patients underwent surgical treatment. Postoperative pathological and immunohistochemical examination can confirm the diagnosis. No patients without tumor recurrence or metastasis during follow-up period. CONCLUSION Altogether, the clinical symptoms of rare BLTs lack specificity, and their preoperative diagnosis largely depends on imaging examination, with a low diagnostic accuracy rate and high chances of misdiagnosis as HCC. Diagnosis is confirmed by pathological and immunohistochemical examination. Surgical resection for rare BLT is safe and effective, regular postoperative follow-up is necessary.
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Affiliation(s)
- Laihui Luo
- Department of General Surgery, First Affiliated Hospital of Nanchang University, 17 Yong Wai Zheng Street, Nanchang, 330006, Jiangxi, China
| | - Tao Wang
- Department of Day Surgery Ward, First Affiliated Hospital of Nanchang University, 17 Yong Wai Zheng Street, Nanchang, 330006, Jiangxi, China
| | - Mengting Cheng
- Department of General Surgery, First Affiliated Hospital of Nanchang University, 17 Yong Wai Zheng Street, Nanchang, 330006, Jiangxi, China
| | - Xian Ge
- Department of Pathology, First Affiliated Hospital of Nanchang University, 17 Yong Wai Zheng Street, Nanchang, 330006, Jiangxi, China
| | - Shengjiang Song
- Department of General Surgery, First Affiliated Hospital of Nanchang University, 17 Yong Wai Zheng Street, Nanchang, 330006, Jiangxi, China
| | - Guoqing Zhu
- Department of General Surgery, First Affiliated Hospital of Nanchang University, 17 Yong Wai Zheng Street, Nanchang, 330006, Jiangxi, China
| | - Yongqiang Xiao
- Department of General Surgery, First Affiliated Hospital of Nanchang University, 17 Yong Wai Zheng Street, Nanchang, 330006, Jiangxi, China
| | - Wei Deng
- Department of General Surgery, First Affiliated Hospital of Nanchang University, 17 Yong Wai Zheng Street, Nanchang, 330006, Jiangxi, China
| | - Jin Xie
- Department of General Surgery, First Affiliated Hospital of Nanchang University, 17 Yong Wai Zheng Street, Nanchang, 330006, Jiangxi, China
| | - Renfeng Shan
- Department of General Surgery, First Affiliated Hospital of Nanchang University, 17 Yong Wai Zheng Street, Nanchang, 330006, Jiangxi, China.
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26
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Gatti M, Maino C, Tore D, Carisio A, Darvizeh F, Tricarico E, Inchingolo R, Ippolito D, Faletti R. Benign focal liver lesions: The role of magnetic resonance imaging. World J Hepatol 2022; 14:923-943. [PMID: 35721295 PMCID: PMC9157713 DOI: 10.4254/wjh.v14.i5.923] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2021] [Revised: 08/07/2021] [Accepted: 04/09/2022] [Indexed: 02/06/2023] Open
Abstract
Liver lesions are common findings in radiologists' daily routine. They are a complex category of pathology that range from solitary benign lesions to primary liver cancer and liver metastases. Benign focal liver lesions can arise from different liver cell types: Epithelial (hepatocytes and biliary cells) and nonepithelial (mesenchymal cells). Liver magnetic resonance imaging (MRI) is a fundamental radiological method in these patients as it allows with its multiparametric approach optimal non-invasive tissue characterization. Furthermore, advanced liver MRI techniques such as diffusion-weighted imaging and hepatobiliary contrast agents have improved the detection of focal liver lesions and can be highly effective in differentiating pseudotumor from tumors, as well as benign from malignant lesions, and can also be used for differential diagnosis. Although histological examination can be useful in making a definitive diagnosis, MRI is an important modality in the diagnosis of liver lesions with a significant impact on patient care. This aim of this review is to provide a comprehensive overview of benign liver lesions on MRI.
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Affiliation(s)
- Marco Gatti
- Department of Surgical Sciences, University of Turin, Turin 10126, Italy.
| | - Cesare Maino
- Department of Diagnostic Radiology, Ospedale San Gerardo, Monza 20900, Italy
| | - Davide Tore
- Department of Surgical Sciences, University of Turin, Turin 10126, Italy
| | - Andrea Carisio
- Department of Surgical Sciences, University of Turin, Turin 10126, Italy
| | - Fatemeh Darvizeh
- School of Medicine, Vita-Salute San Raffaele University, Milan 20121, Japan
| | | | - Riccardo Inchingolo
- Interventional Radiology Unit, "F. Miulli" Regional General Hospital, Acquaviva delle Fonti 70021, Italy
| | - Davide Ippolito
- Department of Diagnostic Radiology, School of Medicine, University of Milano-Bicocca, Monza 20900, Italy
| | - Riccardo Faletti
- Department of Surgical Sciences, University of Turin, Turin 10126, Italy
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27
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Haring MP, Peeks F, Oosterveer MH, Brouwers MC, Hollak CE, Janssen MC, Langendonk JG, Rennings AJ, Wagenmakers MA, Verkade HJ, Derks TG, de Meijer VE. High childhood serum triglyceride concentrations associate with hepatocellular adenoma development in patients with glycogen storage disease type Ia. JHEP Rep 2022; 4:100512. [PMID: 35811762 PMCID: PMC9263528 DOI: 10.1016/j.jhepr.2022.100512] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2022] [Revised: 05/17/2022] [Accepted: 05/18/2022] [Indexed: 12/17/2022] Open
Abstract
Background & Aims Glycogen storage disease type Ia (GSDIa) is an inborn error of carbohydrate metabolism caused by pathogenic variants in the glucose-6-phosphatase catalytic subunit 1 (G6PC1) gene and is associated with hepatocellular adenoma (HCA) formation. Data on risk factors for HCA occurrence in GSDIa are scarce. We investigated HCA development in relation to sex, G6PC1 genotype, and serum triglyceride concentration (TG). Methods An observational study of patients with genetically confirmed GSDIa ≥12 years was performed. Patients were categorised for sex; presence of 2, 1, or 0 predicted severe G6PC1 variant (PSV); and median TG during childhood (<12 years; stratified for above/below 5.65 mmol/L, i.e. 500 mg/dl). Results Fifty-three patients (23 females) were included, of which 26 patients developed HCA at a median (IQR) age of 21 (17–25) years. At the age of 25 years, 48% of females and 30% of males had developed HCA (log-rank p = 0.045). Two-thirds of patients with GSDIa carried 2 PSVs, 20% carried 1, and 13% carried none. Neither the number of PSVs nor any specific G6PC1 variants were associated with HCA occurrence. Childhood TG was 3.4 (3.0–4.2) mmol/L in males vs. 5.6 (4.0–7.9) mmol/L in females (p = 0.026). Childhood TG >5.65 mmol/L was associated with HCA development at younger age, compared with patients with childhood TG <5.65 mmol/L (18 vs. 33 years; log-rank p = 0.001). Cox regression analysis including TG, sex, and TG–sex interaction correction revealed childhood TG >5.65 mmol/L as an independent risk factor for HCA development (hazard ratio [HR] 6.0; 95% CI 1.2–29.8; p = 0.028). Conclusions In patients with GSDIa, high childhood TG was associated with an increased risk of HCA, and earlier onset of HCA development, independent of sex-associated hypertriglyceridaemia, and G6PC1 genotype. Lay summary Glycogen storage disease type Ia (GSDIa) is a rare, inherited metabolic disease that can be complicated by liver tumours (hepatocellular adenomas), which in turn may cause bleeding or progress to liver cancer. Risk factors associated with hepatocellular adenoma formation in patients with GSDIa are largely unknown. In our study, we found that high serum triglyceride concentrations during childhood, but not specific genetic variants, were associated with increased risk of hepatocellular adenoma diagnosis later in life.
Glycogen storage disease Ia (GSDIa) is a metabolic disease caused by mutations in glucose-6-phosphatase catalytic subunit 1 (G6PC1). Patients with GSDIa often develop hepatocellular adenoma (HCA), with unclear risk factors. Metabolic control in GSDIa is commonly evaluated through serum triglyceride concentration (TG). Patients with GSDIa with high childhood TG had increased risk and earlier onset of HCA. Sex-associated hypertriglyceridaemia and G6PC1 genotype were not associated with HCA.
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Affiliation(s)
- Martijn P.D. Haring
- Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Fabian Peeks
- Department of Metabolic Diseases, Beatrix Children’s Hospital, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Maaike H. Oosterveer
- Department of Pediatrics, Center for Liver Digestive and Metabolic Diseases, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Martijn C.G.J. Brouwers
- Department of Internal Medicine, Division of Endocrinology and Metabolic Disease, Maastricht University Medical Center+, Maastricht, the Netherlands
| | - Carla E.M. Hollak
- Department of Endocrinology and Metabolism, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands
| | - Mirian C.H. Janssen
- Department of Internal Medicine, Radboud University Medical Centre, Nijmegen, the Netherlands
| | - Janneke G. Langendonk
- Department of Internal Medicine, Center for Lysosomal and Metabolic Diseases, Erasmus University Medical Center, University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Alexander J.M. Rennings
- Department of Internal Medicine, Radboud University Medical Centre, Nijmegen, the Netherlands
| | - Margreet A.E.M. Wagenmakers
- Department of Internal Medicine, Center for Lysosomal and Metabolic Diseases, Erasmus University Medical Center, University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Henkjan J. Verkade
- Pediatric Gastroenterology and Hepatology, Department of Pediatrics, Beatrix Children’s Hospital, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Terry G.J. Derks
- Department of Metabolic Diseases, Beatrix Children’s Hospital, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Vincent E. de Meijer
- Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
- Corresponding author. Address: University of Groningen and University Medical Center Groningen, Hanzeplein 1, 9700 RB, Groningen, the Netherlands. Tel.: +31 50 361 2896; fax: +31 50 361 4873.
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Liu Y, Liu YZ, Sun L, Zen Y, Inomoto C, Yeh MM. Subtyping of hepatocellular adenoma: a machine learning-based approach. Virchows Arch 2022; 481:49-61. [PMID: 35389097 DOI: 10.1007/s00428-022-03311-w] [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: 10/31/2021] [Revised: 03/08/2022] [Accepted: 03/13/2022] [Indexed: 11/26/2022]
Abstract
Subtyping of hepatocellular adenoma (HCA) is an important task in practice as different subtypes may have different clinical outcomes and management algorithms. Definitive subtyping is currently dependent on immunohistochemical and molecular testing. The association between some morphologic/clinical features and HCA subtypes has been reported; however, the predictive performance of these features has been controversial. In this study, we attempted machine learning based methods to select an efficient and parsimonious set of morphologic/clinical features for differentiating a HCA subtype from the others, and then assessed the performance of the selected features in identifying the correct subtypes. We first examined 50 liver HCA resection specimens collected at the University of Washington and Kobe University/Kings College London, including HNF1α-mutated HCA (H-HCA) (n = 16), inflammatory HCA (I-HCA) (n = 20), beta-catenin activated HCA (β-HCA) (n = 8), and unclassified HCA (U-HCA) (n = 6). Twenty-six morphologic/clinical features were assessed. We used LASSO (least absolute shrinkage and selection operator) to select key features that could differentiate a subtype from the others. We further performed SVM (support vector machine) analysis to assess the performance (sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy) of the selected features in HCA subtyping in an independent cohort of liver resection samples (n = 20) collected at the University of Wisconsin-Madison. With some overlap, different combinations of morphologic/clinical features were selected for each subtype. Based on SVM analysis, the selected features classified HCA into correct subtypes with an overall accuracy of at least 80%. Our findings are useful for initial diagnosis and subtyping of HCA, especially in clinical settings without access to immunohistochemical and molecular assays.
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Affiliation(s)
- Yongjun Liu
- Department of Pathology and Laboratory Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Yao-Zhong Liu
- Department of Biostatistics and Data Science, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, USA
| | - Lifu Sun
- Department of Biostatistics and Data Science, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, USA
| | - Yoh Zen
- Department of Diagnostic Pathology, Kobe University Graduate School of Medicine, Kobe, Japan
- Institute of Liver Studies, King's College Hospital & King's College London, London, UK
| | - Chie Inomoto
- Department of Pathology, Tokai University, Isehara, Japan
| | - Matthew M Yeh
- Department of Laboratory Medicine and Pathology, University of Washington School of Medicine, 1959 NE Pacific Street, NE140D, Seattle, WA, 98195-6100, USA.
- Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA.
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29
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Aziz H, Brown ZJ, Eskander MF, Aquina CT, Baghdadi A, Kamel IR, Pawlik TM. A Scoping Review of the Classification, Diagnosis, and Management of Hepatic Adenomas. J Gastrointest Surg 2022; 26:965-978. [PMID: 35083725 DOI: 10.1007/s11605-022-05246-8] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2021] [Accepted: 01/05/2022] [Indexed: 01/31/2023]
Abstract
BACKGROUND Hepatic adenomas (HA), or hepatocellular adenomas, are benign, solid liver lesions that develop in otherwise normal livers, often in the setting of increased estrogen levels. While considered a benign tumor, there is a risk for substantial complications such as hemorrhage and malignant transformation. We review the diagnosis, classification, and potential therapeutic management options for patients with HA. METHODS A scoping narrative review was conducted based on recent literature regarding classification, diagnosis, and management of HA. RESULTS While HAs are typically considered benign, complications such as hemorrhage and malignant transformation may occur in approximately 25% and 5% of patients, respectively. Recent advances in imaging and molecular profiling have allowed for the classification of HAs into subtypes allowing for patient risk stratification that helps guide management. Surgical resection should be considered in asymptomatic patients who are male, have an adenoma ≥5 cm in diameter, or have the β-catenin-activated subtype due to an increased risk of hemorrhage and/or malignant transformation. CONCLUSION Molecular profiling has aided in the stratification of patients relative to the risk of complications to predict better the potential behavior of HAs.
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Affiliation(s)
- Hassan Aziz
- Department of Surgery, Tufts University School of Medicine, Boston, MA, USA
| | - Zachary J Brown
- Department of Surgery, The Ohio State University Wexner Medical Center, 395 W. 12th Ave., Suite, Columbus, OH, 670, USA
| | - Mariam F Eskander
- Department of Surgery, The Ohio State University Wexner Medical Center, 395 W. 12th Ave., Suite, Columbus, OH, 670, USA
| | - Christopher T Aquina
- Department of Surgery, The Ohio State University Wexner Medical Center, 395 W. 12th Ave., Suite, Columbus, OH, 670, USA
| | | | - Ihab R Kamel
- Department of Radiology, Johns Hopkins University, Baltimore, MD, USA
| | - Timothy M Pawlik
- Department of Surgery, The Ohio State University Wexner Medical Center, 395 W. 12th Ave., Suite, Columbus, OH, 670, USA.
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30
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Desjonqueres E, Campani C, Marra F, Zucman-Rossi J, Nault JC. Preneoplastic lesions in the liver: Molecular insights and relevance for clinical practice. Liver Int 2022; 42:492-506. [PMID: 34982503 DOI: 10.1111/liv.15152] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2021] [Revised: 12/20/2021] [Accepted: 12/22/2021] [Indexed: 12/12/2022]
Abstract
Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) are the most frequent primary liver cancers, accounting for approximately 80% and 15%, respectively. HCC carcinogenesis occurs mostly in cirrhosis and is a complex multi-step process, from precancerous lesions (low-grade and high-grade dysplastic nodules) to progressed HCC. During the different stages of liver carcinogenesis, there is an accumulation of pathological, genetic and epigenetic changes leading to initiation, malignant transformation and finally tumour progression. In contrast, a small subset of HCC occurs in normal liver from the transformation of hepatocellular adenoma (HCA), a benign hepatocellular tumour. The recent molecular classification enables to stratify HCAs according to their risk of complication, in particular malignant transformation, associated with mutations in exon 3 of the catenin beta 1 (CTNNB1) gene. Cholangiocarcinoma (CCA) derives from the multistep malignant transformation of preneoplastic lesions, like biliary intraepithelial neoplasia (BilIN) and intraductal papillary neoplasm of the bile duct (IPNB), for which a pre-operative diagnosis remains difficult. Different genetic alterations are involved in BilIN and IPNB progression, leading to the development of tubular or intestinal adenocarcinoma. The aims of this review are to describe the main clinical and molecular features of preneoplastic lesions leading to the development of HCC and CCA, their implications in clinical practice and the perspectives for future research.
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Affiliation(s)
- Elvire Desjonqueres
- Service d'hépatologie, Hôpital Avicenne, Hôpitaux Universitaires Paris-Seine-Saint-Denis, Assistance-Publique Hôpitaux de Paris, Bobigny, France.,Unité de Formation et de Recherche Santé Médecine et Biologie Humaine, Université Paris 13, Communauté d'Universités et Etablissements Sorbonne Paris Cité, Paris, France.,Centre de Recherche des Cordeliers, Sorbonne Université, Inserm, Université de Paris, team « Functional Genomics of Solid Tumors », Paris, France.,Equipe labellisée Ligue Nationale Contre le Cancer, Labex OncoImmunology, Paris, France
| | - Claudia Campani
- Unité de Formation et de Recherche Santé Médecine et Biologie Humaine, Université Paris 13, Communauté d'Universités et Etablissements Sorbonne Paris Cité, Paris, France.,Centre de Recherche des Cordeliers, Sorbonne Université, Inserm, Université de Paris, team « Functional Genomics of Solid Tumors », Paris, France.,Equipe labellisée Ligue Nationale Contre le Cancer, Labex OncoImmunology, Paris, France.,Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Fabio Marra
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Jessica Zucman-Rossi
- Centre de Recherche des Cordeliers, Sorbonne Université, Inserm, Université de Paris, team « Functional Genomics of Solid Tumors », Paris, France.,Equipe labellisée Ligue Nationale Contre le Cancer, Labex OncoImmunology, Paris, France.,Hôpital Européen Georges Pompidou, APHP, Paris, France
| | - Jean-Charles Nault
- Service d'hépatologie, Hôpital Avicenne, Hôpitaux Universitaires Paris-Seine-Saint-Denis, Assistance-Publique Hôpitaux de Paris, Bobigny, France.,Unité de Formation et de Recherche Santé Médecine et Biologie Humaine, Université Paris 13, Communauté d'Universités et Etablissements Sorbonne Paris Cité, Paris, France.,Centre de Recherche des Cordeliers, Sorbonne Université, Inserm, Université de Paris, team « Functional Genomics of Solid Tumors », Paris, France.,Equipe labellisée Ligue Nationale Contre le Cancer, Labex OncoImmunology, Paris, France
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Abstract
Hepatocellular adenoma (HCA) is a rare and benign liver tumor that affects predominantly young and middle-aged women, especially between 30–40 years old. Liver adenomatosis (LA) is defined as the presence of 10 or more HCA. There are authors that report eight different subtypes of HCA, that correlates with clinical and histopathological features, being the inflammatory subtype the most common. We present a case of a 32-year-old Caucasian woman with a history of self-limited episodes of right abdominal pain and an abdominal ultrasound with multiple hypoechogenic liver nodules, suspected of metastasis. She was taking combined oral contraceptive for 6 years. Magnetic Resonance Imaging (MRI) disclosed around 40 nodules, suggestive of HCA. Liver biopsy confirmed HCA, inflammatory subtype. Oral contraceptive was stopped and control MRI 6 months later disclosed reduction of nodules’ dimensions. Management of patients with LA should be based on the size of the largest tumor, as clinical presentation and risk of bleeding or malignancy do not differ between patients with single or multiple HCAs. However, even with biopsy, there is a risk of missampling, raising concern about the real risk of bleeding and malignant potential in patients with different subtypes coexisting in the same liver.
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32
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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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33
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Ziogas IA, Tasoudis PT, Serifis N, Alexopoulos SP, Montenovo MI, Shingina A. Liver Transplantation for Hepatic Adenoma: A UNOS Database Analysis and Systematic Review of the Literature. Transplant Direct 2022; 8:e1264. [PMID: 35018302 PMCID: PMC8735769 DOI: 10.1097/txd.0000000000001264] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2021] [Revised: 10/01/2021] [Accepted: 10/25/2021] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Liver transplantation (LT) has been employed for hepatic adenoma (HA) on a case-oriented basis. We aimed to describe the characteristics, waitlist, and post-LT outcomes of patients requiring LT for HA. METHODS All patients listed or transplanted for HA in the United States were identified in the United Network for Organ Sharing (UNOS) database (1987-2020). A systematic literature review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis statement. RESULTS A total of 199 HA patients were listed for LT in UNOS and the crude waitlist mortality was 9.0%. A total of 142 HA patients underwent LT; 118 of these were among those listed with an indication of HA who underwent LT, and 24 were diagnosed incidentally. Most did not experience hepatocellular carcinoma transformation (89.4%). Over a median follow-up of 62.9 mo, death was reported in 18.3%. The 1-, 3-, and 5-y patient survival rates were 94.2%, 89.7%, and 86.3% in the UNOS cohort. The systematic review yielded 61 articles reporting on 99 nonoverlapping patients undergoing LT for HA and 2 articles reporting on multicenter studies. The most common LT indications were suspected malignancy (39.7%), unresectable HA (31.7%), and increasing size (27.0%), whereas 53.1% had glycogen storage disease. Over a median follow-up of 36.5 mo, death was reported in 6.0% (n=5/84). The 1-, 3-, and 5-y patient survival rates were all 95.0% in the systematic review. CONCLUSIONS LT for HA can lead to excellent long-term outcomes in well-selected patients. Prospective granular data are needed to develop more optimal selection criteria and further improve outcomes.
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Affiliation(s)
- Ioannis A. Ziogas
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Vanderbilt University Medical Center, Nashville, TN
- Surgery Working Group, Society of Junior Doctors, Athens, Greece
| | - Panagiotis T. Tasoudis
- Surgery Working Group, Society of Junior Doctors, Athens, Greece
- School of Health Sciences, University of Thessaly, Larissa, Greece
| | - Nikolaos Serifis
- Surgery Working Group, Society of Junior Doctors, Athens, Greece
- Division of Transplantation, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Sophoclis P. Alexopoulos
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Vanderbilt University Medical Center, Nashville, TN
| | - Martin I. Montenovo
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Vanderbilt University Medical Center, Nashville, TN
| | - Alexandra Shingina
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN
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Nault JC, Blanc JF, Moga L, Calderaro J, Dao T, Guiu B, Hocquelet A, Paradis V, Salamé E, de Lédinghen V, Bourlière M, Bureau C, Ganne-Carrié N. Non-invasive diagnosis and follow-up of benign liver tumours. Clin Res Hepatol Gastroenterol 2022; 46:101765. [PMID: 34333196 DOI: 10.1016/j.clinre.2021.101765] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2021] [Accepted: 07/23/2021] [Indexed: 02/04/2023]
Abstract
Hepatocellular benign liver tumours are mainly developed on normal liver and include hepatic hemangioma, focal nodular hyperplasia and hepatocellular adenoma from the most frequent to the less frequent. The diagnosis of hepatic hemangioma and of simple hepatic biliary cysts can be performed using non-invasive criteria using liver ultrasonography or contrast enhanced MRI. Most of the time the diagnosis of focal nodular hyperplasia can be achieved using contrast-enhanced ultrasonography or contrast enhanced MRI with an additional value of hepatobiliary contrast-agent in this setting. Rarely, if a doubt persists, a tumour and non-tumour liver biopsy can be required in order to establish the diagnosis. As hepatic hemangioma, simple hepatic biliary cysts and focal nodular hyperplasia are not associated with complications, they don't require any treatments or follow-up. Hepatocellular adenomas are mainly diagnosed at histology on surgical samples or liver biopsy even if some radiological features are highly suggestive of several subtypes of hepatocellular adenomas. Finally, the management of hepatocellular adenomas should be guided according to the tumour size, gender but also to the molecular subtypes.
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Affiliation(s)
- Jean-Charles Nault
- Service d'hépatologie, Hôpital Avicenne, APHP; Université Sorbonne Paris Nord, Bobigny & INSERM UMR 1138, Centre de Recherche des Cordeliers, Université de Paris France.
| | - Jean-Frédéric Blanc
- Service d'hépato-gastroentérologie et d'oncologie digestive, Hôpital Haut-Lévêque, CHU Bordeaux, Pessac & INSERM U1053, Université de Bordeaux, Bordeaux France
| | - Lucile Moga
- Service d'Hépatologie et Transplantation Hépatique, Hôpital Beaujon, APHP, Clichy France
| | - Julien Calderaro
- Service de département de pathologie, Hôpital Henri-Mondor, APHP, Créteil France
| | - Thông Dao
- Service d'hépato-gastro-entérologie et nutrition, CHU Caen Normandie, Caen France
| | - Boris Guiu
- Service de radiologie diagnostique et interventionnelle Saint Eloi, CHU Montpellier, Montpellier France
| | - Arnaud Hocquelet
- Service de radiodiagnostic et radiologie interventionnelle, CHUV Lausanne, Lausanne Switzerland
| | | | - Ephrem Salamé
- Unité de Chirurgie Digestive Endocrinienne et Bariatrique, CHU Tours, Tours France
| | - Victor de Lédinghen
- Service d'hépato-gastroentérologie et d'oncologie digestive, Hôpital Haut-Lévêque, CHU Bordeaux, Pessac & INSERM U1053, Université de Bordeaux, Bordeaux France
| | - Marc Bourlière
- Service d'hépato-gastroentérologie, Hôpital Saint Joseph & INSERM UMR 1252 IRD SESSTIM Aix Marseille Université, Marseille
| | - Christophe Bureau
- Service d'hépatologie, Hôpital Rangueil, CHU Toulouse, Toulouse France
| | - Nathalie Ganne-Carrié
- Service d'hépatologie, Hôpital Avicenne, APHP; Université Sorbonne Paris Nord, Bobigny & INSERM UMR 1138, Centre de Recherche des Cordeliers, Université de Paris France
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35
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Bioulac-Sage P, Gouw ASH, Balabaud C, Sempoux C. Hepatocellular Adenoma: What We Know, What We Do Not Know, and Why It Matters. Histopathology 2021; 80:878-897. [PMID: 34856012 DOI: 10.1111/his.14605] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2021] [Revised: 11/21/2021] [Accepted: 11/25/2021] [Indexed: 11/27/2022]
Abstract
In the last 2 decades there has been significant progress in research and diagnosis of hepatocellular adenoma (HCA), resulting in the establishment of a molecular and immunohistological HCA classification. This review aims to fine-tune the current expertise in order to enhance the histopathological diagnostic possibilities, by refining issues that are already known, addressing diagnostic difficulties and identifying still unknown aspects of HCA. We will discuss novel methods to identify HCA subtypes, in particular the sonic hedgehog HCAs and the interpretation of glutamine synthetase patterns for the recognition of beta-catenin mutated HCAs. The major complications of HCAs, bleeding and malignant transformation, will be considered, including the dilemmas of atypical and borderline lesions. Paragraphs on HCAs in different clinical and geographical settings, e.g. pregnancy, cirrhosis and non-western countries are included. The natural history of the different HCA subtypes in relation with age, sex and risk factors is a feature still insufficiently investigated. This is also true for the risks of clinical bleeding and malignant transformation in association with HCA subtypes. As HCA is a relatively rare tumor, a multicenter and multidisciplinary approach across geographical boundaries will be the appropriate method to establish prospective programs to identify, classify and manage HCAs, focusing on several aspects, e.g. etiology, underlying liver disease, complications, regression and growth. Updating what we know, identifying and addressing features that we do not know matters to warrant optimal patient management.
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Affiliation(s)
| | - Annette S H Gouw
- Departement of Pathology and Medical Biology, University Medical Center Groningen, Groningen, the Netherlands
| | | | - Christine Sempoux
- Service of Clinical Pathology, Institute of Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
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Agnello F, Rabiolo L, Midiri F, Lo Re G, Grassedonio E, La Grutta L, Buscemi S, Agrusa A, Galia M. Focal hepatic intrinsically hyperattenuating lesions at unenhanced CT: Not always calcifications. Clin Imaging 2021; 80:304-314. [PMID: 34482241 DOI: 10.1016/j.clinimag.2021.08.020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2021] [Revised: 07/26/2021] [Accepted: 08/13/2021] [Indexed: 11/27/2022]
Abstract
Due to the growing use of CT, there has been an increase in the frequency of detecting focal liver lesions. Intrinsically hyperattenuating hepatic lesions or pseudolesions are not uncommon at unenhanced CT. Hyperattenuating hepatic lesions can be divided into non-calcified and calcified. Causes of intrinsic hyperattenuation include hemorrhage, thrombosis, and calcifications. Focal liver lesions can show hyperattenuation on unenhanced CT in case of severe liver steatosis. Recognition of etiologies associated with hyperattenuation on unenhanced CT can help the radiologist in characterizing focal liver lesions and pseudolesions. In this paper, we describe the spectrum of intrinsically hyperattenuating focal liver lesions and pseudolesions at unenhanced CT.
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Affiliation(s)
- Francesco Agnello
- Section of Radiological Sciences, Department of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo, Palermo, Italy
| | - Lidia Rabiolo
- Section of Radiological Sciences, Department of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo, Palermo, Italy
| | - Federico Midiri
- Section of Radiological Sciences, Department of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo, Palermo, Italy
| | - Giuseppe Lo Re
- Section of Radiological Sciences, Department of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo, Palermo, Italy
| | - Emanuele Grassedonio
- Section of Radiological Sciences, Department of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo, Palermo, Italy
| | - Ludovico La Grutta
- Section of Radiological Sciences, Department of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo, Palermo, Italy
| | - Salvatore Buscemi
- Department of Surgical, Oncological and Oral Sciences, University of Palermo, Palermo, Italy
| | - Antonino Agrusa
- Department of Surgical, Oncological and Oral Sciences, University of Palermo, Palermo, Italy
| | - Massimo Galia
- Section of Radiological Sciences, Department of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo, Palermo, Italy.
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Shyu S, Ali SZ. Significance of hepatocyte atypia in liver fine needle aspiration. Diagn Cytopathol 2021; 50:186-195. [PMID: 34459153 DOI: 10.1002/dc.24851] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2021] [Revised: 08/04/2021] [Accepted: 08/05/2021] [Indexed: 11/06/2022]
Abstract
Fine needle aspiration (FNA) of the liver is frequently the diagnostic procedure of choice for sampling hepatic lesions. One of the main diagnostic challenges in the interpretation of liver FNA is distinguishing dysplastic lesions and well-differentiated hepatocellular carcinoma (WD-HCC) from benign processes, as they share significant cytomorphologic overlap. Furthermore, the diagnosis of HCC often requires evaluation of stroma for invasion, which may not be present on cytology and small needle biopsy specimens. A reporting system for liver cytopathology has yet to be instituted. Without standardized and well-defined criteria for hepatocyte atypia, we recommend limiting the use of atypia in evaluation of liver FNA specimens to describe a diagnosis of exclusion, in which all known benign and neoplastic processes have been ruled out. The cytologic findings on the FNA of a liver nodule may be best reported as atypical hepatocytes in the absence of a core needle biopsy or cell block sufficient to render a definitive diagnosis of HCC.
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Affiliation(s)
- Susan Shyu
- Department of Pathology, Johns Hopkins University, Baltimore, Maryland, USA
| | - Syed Z Ali
- Department of Pathology, Johns Hopkins University, Baltimore, Maryland, USA
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38
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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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Hepatocellular Adenoma Risk Factors of Hemorrhage: Size is not the only Concern! Single Center Retrospective Experience of 261 Patients. Ann Surg 2021; 274:843-850. [PMID: 34334644 DOI: 10.1097/sla.0000000000005108] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
OBJECTIVE Our aim was to determine independent risk factors of clinical bleeding of hepatocellular adenoma (HCA) in order to define a better management strategy. SUMMARY BACKGROUND DATA HCA is a rare benign liver tumor with severe complications: malignant transformation which is rare (5-8%) and more often, hemorrhage (20-27%). To date, only size > 5 cm and histological subtype (possibly sonic hedgehog) are associated with bleeding, but these criteria are not clearly established. METHODS We retrospectively collected data from a cohort of 268 patients with HCA managed in our tertiary center, from 1984 to 2020 and focused on clinical bleeding. Hemorrhage was considered as severe when it required intensive care and moderate when bleeding symptoms required a hospitalization. We included 261 patients, of which 130 (49.8%) had multiple HCAs or liver adenomatosis. All surgical specimen and liver biopsy were reviewed by an experienced liver pathologist and reclassified in the light of the current immunohistochemistry. Mean duration of follow-up was 93.3 months (range 1-363). We analyzed type, frequency, consequences of bleeding and risk factors among clinical data and HCA characteristics. RESULTS Eighty-three HCA (31.8%) were hemorrhagic. There were 4 pregnant women with one newborn death. One patient died before treatment. Surgery was performed in 78 (94.0%) patients. Mortality was nil and severe complications occurred in 11.5%. Multivariate analysis identified size (OR 1.02 [1.01-1.02], p < 0.001), shHCA (OR 21.02 [5.05-87.52], p < 0.001), b-catenin mutation on exon 7/8 (OR 6.47 [1.78-23.55], p = 0.0046), chronic alcohol consumption (OR 9.16 [2.47-34.01], p < 0.001) as independent risk factors of clinical bleeding. CONCLUSIONS This series, focused on the hemorrhagic risk of HCA, shows that size, but rather more molecular subtype is determinant in the natural history of HCA.
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40
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Sureka B, Rastogi A, Mukund A, Sarin SK. False-positive 18F fluorodeoxyglucose positron emission tomography-avid benign hepatic tumor: Previously unreported in a male patient. Indian J Radiol Imaging 2021; 28:200-204. [PMID: 30050244 PMCID: PMC6038214 DOI: 10.4103/ijri.ijri_170_17] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
We report a case of 18F fluorodeoxyglucose (FDG) positron emission tomography (PET)–computed tomography-avid histologically confirmed inflammatory hepatic adenoma in a 77-year-old male patient without any history of steroid, alcohol use. This is the first case report of inflammatory hepatic adenoma in a male patient documented in the published literature showing uptake on 18F-FDG PET. Previous single case report of 18F-FDG PET-avid hepatic adenoma in a male patient was of hepatocyte nuclear factor-1-α subtype.
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Affiliation(s)
- Binit Sureka
- Department of Radiology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Archana Rastogi
- Department of Pathology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Amar Mukund
- Department of Radiology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Shiv Kumar Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
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Successful resection of a huge hepatocellular adenoma. Clin J Gastroenterol 2021; 14:1544-1549. [PMID: 34287778 DOI: 10.1007/s12328-021-01486-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/06/2021] [Accepted: 07/17/2021] [Indexed: 10/20/2022]
Abstract
Hepatocellular adenoma (HCA) is a rare benign liver tumor that has been reported to occur particularly more often in women who use contraceptives. A 72-year-old woman with no history of using contraceptives presented to our hospital for further examination of a liver tumor. Contrast-enhanced computed tomography and gadoxetic acid-enhanced magnetic resonance imaging revealed a huge solitary hepatic tumor measuring 83 × 76 mm in segments 4, 5, and 8. The differential diagnoses were cholangiocarcinoma and mixed-type hepatocellular carcinoma. Percutaneous needle biopsies were performed twice, and no malignant components were found. Central bi-segmentectomy of the liver was successfully performed. Immunohistochemical staining showed that β-catenin was positive in the membrane of the tumor cells, while fatty acid-binding protein, glutamine synthetase, and amyloid A were negative. These results led to a diagnosis of HCA, hepatocyte nuclear factor-1α-inactivated subtype. The patient's postoperative course was uneventful, and she developed no recurrence for 10 months after surgery. We experienced a rare case of benign HCA. Obtaining a correct preoperative diagnosis is sometimes difficult at the first evaluation. HCA should be considered as a differential diagnosis of liver tumors.
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Herman P, Fonseca GM, Kruger JAP, Jeismann VB, Coelho FF. Guidelines for the Treatment of Hepatocellular Adenoma in the Era of Molecular Biology: An Experience-Based Surgeons' Perspective. J Gastrointest Surg 2021; 25:1494-1502. [PMID: 32666496 DOI: 10.1007/s11605-020-04724-1] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2020] [Accepted: 06/28/2020] [Indexed: 01/31/2023]
Abstract
BACKGROUND Hepatocellular adenoma (HA) is a rare benign liver tumor with increasing incidence affecting young women. In the last years, much has changed in diagnosis, classification, and treatment, due to the identification of different molecular subtypes. With the evolving knowledge, especially on molecular characteristics of the disease, we are far from a consensus of how to deal with such a multifaceted benign disease METHODS: In the last 20 years, we have treated 134 patients with HA with a mean age of 28 years, being 126 women. Fifty patients had a history of abdominal pain and 13 patients had an acute episode of pain due to rupture and bleeding. Until 2009, adenomas larger than 4 cm in diameter were resected, regardless of gender. From 2010 to 2016, only adenomas larger than 5 cm were referred for surgical treatment. Since 2016, resection was indicated in all female patients with non-steatotic adenomas larger than 5 cm and all adenomas in men. RESULTS AND DISCUSSION One hundred twenty-four patients were submitted to resection, being in 21 major resections. Since 2010, 74% of resections were done laparoscopically. Patients with ruptured adenomas were treated with transarterial embolization. Morbidity rate was 8.1% with no mortality. Authors discuss point-by-point all the aspects and presentations of the disease and the best approach. We proposed a therapeutic guideline based on the best available evidence and in our experience. CONCLUSIONS Due to the complexity of the disease, the treatment of HA is one the best examples of an individualized approach.
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Affiliation(s)
- Paulo Herman
- Digestive Surgery Division, Department of Gastroenterology, University of São Paulo School of Medicine, São Paulo, Brazil.
| | - Gilton Marques Fonseca
- Digestive Surgery Division, Department of Gastroenterology, University of São Paulo School of Medicine, São Paulo, Brazil
| | - Jaime Arthur Pirola Kruger
- Digestive Surgery Division, Department of Gastroenterology, University of São Paulo School of Medicine, São Paulo, Brazil
| | - Vagner Birk Jeismann
- Digestive Surgery Division, Department of Gastroenterology, University of São Paulo School of Medicine, São Paulo, Brazil
| | - Fabricio Ferreira Coelho
- Digestive Surgery Division, Department of Gastroenterology, University of São Paulo School of Medicine, São Paulo, Brazil
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Prabhu M, Passah A, Kansotia V, Singh S. 18-F Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography of a Large Inflammatory-Hepatocellular Adenoma. Indian J Nucl Med 2021; 36:95-96. [PMID: 34040313 PMCID: PMC8130690 DOI: 10.4103/ijnm.ijnm_87_20] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2020] [Revised: 05/15/2020] [Accepted: 05/18/2020] [Indexed: 11/09/2022] Open
Abstract
We report a case of an 81-year-old male evaluated for a liver space-occupying lesion. US-guided biopsy and immunohistochemistry were suggestive of hepatocellular adenoma (HCA)-inflammatory (with telangiectasia). Serial 18-F fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography scans revealed a heterogeneously enhancing hypermetabolic mass in the right lobe of the liver, remaining stable for a span of 3 years. This case highlights that benign rare tumors of the liver such as HCA can be intensely FDG avid and that uptake cannot conclude its malignant transformation.
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Affiliation(s)
- Meghana Prabhu
- Department of Nuclear Medicine, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Averilicia Passah
- Department of Nuclear Medicine, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Vanjul Kansotia
- Department of Nuclear Medicine, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Sandeep Singh
- Department of Nuclear Medicine, Institute of Liver and Biliary Sciences, New Delhi, India
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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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45
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Wong VK, Fung AW, Elsayes KM. Magnetic Resonance Imaging of Hepatic Adenoma Subtypes. Clin Liver Dis (Hoboken) 2021; 17:113-118. [PMID: 33868649 PMCID: PMC8043715 DOI: 10.1002/cld.996] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2020] [Revised: 05/28/2020] [Accepted: 06/13/2020] [Indexed: 02/04/2023] Open
Affiliation(s)
- Vincenzo K. Wong
- Department of Abdominal ImagingThe University of Texas M.D. Anderson Cancer CenterHoustonTX
| | - Alice W. Fung
- Department of Diagnostic RadiologyOregon Health and Science UniversityPortlandOR
| | - Khaled M. Elsayes
- Department of Abdominal ImagingThe University of Texas M.D. Anderson Cancer CenterHoustonTX
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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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Beta-catenin-activated hepatocellular adenoma in a male. Clin J Gastroenterol 2021; 14:831-835. [PMID: 33651269 DOI: 10.1007/s12328-021-01372-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2020] [Accepted: 02/22/2021] [Indexed: 01/14/2023]
Abstract
Beta-catenin-activated hepatocellular adenoma is potentially malignant and warrants careful follow-up and surgical resection. Here, we report a 48-year-old man in whom a 55 mm single liver tumor was incidentally detected in the S1 segment. Contrast-enhanced computed tomography scans showed no enhancement in the early phase and a slight defection in the late phase. The tumor was enhanced hyperintensity in the hepatobiliary phase on Gd-ethoxybenzyl-diethylenetriaminepentaacetic acid-enhanced magnetic resonance imaging. The histologic features of ultrasound-guided fine-needle aspiration biopsy indicated hepatocellular adenoma, and the tumor was immunohistochemically positive for glutamine synthetase and β-catenin. Considering the risk of malignant transformation, he underwent laparoscopic-assisted partial liver resection. The resected tumor did not contain any malignant lesions. This case indicates that aspiration needle biopsy and immunohistochemistry were useful for histological diagnosis and treatment decisions based on the molecular definition of hepatocellular adenoma.
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Auer TA, Walter-Rittel T, Geisel D, Schöning W, Schmelzle M, Müller T, Sinn B, Denecke T, Hamm B, Fehrenbach U. HBP-enhancing hepatocellular adenomas and how to discriminate them from FNH in Gd-EOB MRI. BMC Med Imaging 2021; 21:28. [PMID: 33588783 PMCID: PMC7885421 DOI: 10.1186/s12880-021-00552-0] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2020] [Accepted: 01/19/2021] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Recent studies provide evidence that hepatocellular adenomas (HCAs) frequently take up gadoxetic acid (Gd-EOB) during the hepatobiliary phase (HBP). The purpose of our study was to investigate how to differentiate between Gd-EOB-enhancing HCAs and focal nodular hyperplasias (FNHs). We therefore retrospectively included 40 HCAs classified as HBP Gd-EOB-enhancing lesions from a sample of 100 histopathologically proven HCAs in 65 patients. These enhancing HCAs were matched retrospectively with 28 FNH lesions (standard of reference: surgical resection). Two readers (experienced abdominal radiologists blinded to clinical data) reviewed the images evaluating morphologic features and subjectively scoring Gd-EOB uptake (25-50%, 50-75% and 75-100%) for each lesion. Quantitative lesion-to-liver enhancement was measured in arterial, portal venous (PV), transitional and HBP. Additionally, multivariate regression analyses were performed. RESULTS Subjective scoring of intralesional Gd-EOB uptake showed the highest discriminatory accuracies (AUC: 0.848 (R#1); 0.920 (R#2)-p < 0.001) with significantly higher uptake scores assigned to FNHs (Cut-off: 75%-100%). Typical lobulation and presence of a central scar in FNH achieved an accuracy of 0.750 or higher in at least one reader (lobulation-AUC: 0.809 (R#1); 0.736 (R#2); central scar-AUC: 0.595 (R#1); 0.784 (R#2)). The multivariate regression emphasized the discriminatory power of the Gd-EOB scoring (p = 0.001/OR:22.15 (R#1) and p < 0.001/OR:99.12 (R#2). The lesion-to-liver ratio differed significantly between FNH and HCA in the PV phase and HBP (PV: 132.9 (FNH) and 110.2 (HCA), p = 0.048 and HBP: 110.3 (FNH) and 39.2 (HCA), p < 0.001)), while the difference was not significant in arterial and transitional contrast phases (p > 0.05). CONCLUSION Even in HBP-enhancing HCA, characterization of Gd-EOB uptake was found to provide the strongest discriminatory power in differentiating HCA from FNH. Furthermore, a lobulated appearance and a central scar are more frequently seen in FNH than in HCA.
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Affiliation(s)
- Timo Alexander Auer
- Klinik Für Radiologie, Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany.
- Berlin Institute of Health (BIH), Anna-Louisa-Karsch-Straße 2, 10178, Berlin, 10178, Germany.
| | - Thula Walter-Rittel
- Klinik Für Radiologie, Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany
| | - Dominik Geisel
- Klinik Für Radiologie, Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany
| | - Wenzel Schöning
- Department of Surgery, Campus Charité Mitte | Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, Berlin, 13353, Germany
| | - Moritz Schmelzle
- Department of Surgery, Campus Charité Mitte | Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, Berlin, 13353, Germany
| | - Tobias Müller
- Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie, Campus Virchow Klinikum, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Bruno Sinn
- Institute of Pathology, Charité - Universitätsmedizin Berlin, Charitéplatz 1, Berlin, 10117, Germany
| | - Timm Denecke
- Department of Diagnostic and Interventional Radiology, Universitätsklinikum Leipzig, Liebigstraße 20, Leipzig, 04103, Germany
| | - Bernd Hamm
- Klinik Für Radiologie, Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany
| | - Uli Fehrenbach
- Klinik Für Radiologie, Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany
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Andrews AR, Putra J. Central Hepatic Regenerative Nodules in Alagille Syndrome: A Clinicopathological Review. Fetal Pediatr Pathol 2021; 40:69-79. [PMID: 31608763 DOI: 10.1080/15513815.2019.1675834] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2019] [Revised: 09/18/2019] [Accepted: 09/24/2019] [Indexed: 10/25/2022]
Abstract
OBJECTIVE This review aims to highlight the clinicopathological characteristics and differential diagnosis of central hepatic regenerative nodules (CHRNs) in patients with Alagille syndrome. METHODS A review of the literature for cases of CHRNs and their differential diagnoses in patients with Alagille syndrome was performed and the main findings were collated. RESULTS Large, regenerative hepatic nodules are seen in approximately 30% of patients with Alagille syndrome. They are thought to be a functional adaptation to vascular changes rather than a neoplastic process. The nodules are typically centrally located, and normal hepatic vasculature coursing through the lesions are noted radiologically. Microscopically, they are characterized by well-circumscribed hepatic lesions with preserved architecture, lesser degrees of fibrosis and relative preservation of interlobular bile ducts compared to the background cirrhotic liver. CONCLUSION Regenerative nodules are common in Alagille's syndrome, and should be distinguished from hepatocellular carcinomas and adenomas for appropriate management and prognostication.
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Affiliation(s)
- Alicia R Andrews
- Department of Pathology and Laboratory Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada
| | - Juan Putra
- Hospital for Sick Children, Paediatric Laboratory Medicine, Toronto, Ontario, Canada
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HERMAN P, FONSECA GM, KRUGER JAP, JEISMANN VB, COELHO FF. RESSECÇÃO LAPAROSCÓPICA DE TUMORES BENIGNOS DO FÍGADO: POSIÇÃO ATUAL. ABCD-ARQUIVOS BRASILEIROS DE CIRURGIA DIGESTIVA 2021; 34:e1641. [PMID: 35107503 PMCID: PMC8846456 DOI: 10.1590/0102-672020210002e1641] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/22/2021] [Accepted: 11/25/2021] [Indexed: 11/22/2022]
Abstract
The main indications of the use of laparoscopic liver surgery (LLS), in the early
days, were benign liver lesions. As LLS became more popular, indications for
malignant diseases outnumbered those for benign ones. This study aims to rule
out the indications and results of LLS for the treatment of benign liver
tumors.
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