We took advantage of the reported genotype/phenotype classification to analyze our surgical series of hepatocellular adenoma (HCA). The series without specific known etiologies included 128 cases (116 women). The number of nodules varies from single, <5, and >5 in 78, 38, and 12 cases, respectively. The resection was complete in 95 cases. We identified 46 HNF1␣-inactivated HCAs (44 women), 63 inflammatory HCAs (IHCA, 53 women) of which nine were also -catenin-activated, and seven -catenin-activated HCAs (all women); six additional cases had no known phenotypic marker and six others could not be phenotypically analyzed. Twenty-three of 128 HCAs showed bleeding. No differences were observed in solitary or multiple tumors in terms of hemorrhagic manifestations between groups. In contrast, differences were observed between the two main groups. Steatosis (tumor), microadenomas (resected specimen), and additional benign nodules were more frequently observed in HNF1␣-inactivated HCAs (P < 0.01) than in IHCAs. Body mass index > 25, peliosis (tumor), and steatosis in background liver were more frequent in IHCA (P < 0.01). After complete resection, new HCAs in the centimetric range were more frequently found during follow-up (>1 year) in HNF1␣-inactivated HCA. After incomplete resection (HCA left in nonresected liver), the majority of HCA remained stable in the two main groups and even sometimes regressed. Six patients of 128 developed hepatocellular carcinoma (HCC) (all were -catenin-activated, whether inflammatory or not). Conclusion: There were noticeable clinical differences between HNF1␣-inactivated HCA and IHCA; there was no increased risk of bleeding or HCC related to the number of HCAs; -cateninactivated HCAs are at higher risk of HCC. As a consequence, we believe that management of HCA needs to be adapted to the phenotype of these tumors. (HEPATOLOGY 2009;50:481-489.)
Hepatocellular adenomas (HCAs) are a group of benign tumors forming three molecular pathological subgroups: (1) hepatocyte nuclear factor 1␣ (HNF-1␣)-inactivated, (2) -catenin-activated, and (3) inflammatory. Some HCAs present both -catenin activation and inflammation. We analyzed magnetic resonance imaging (MRI) data for correlations between features on imaging and pathological classification of HCAs. We included 50 cases for which pathology specimens were classified into three groups based on immunohistochemical staining. Two characteristic MRI profiles were identified corresponding to HNF-1␣-inactivated and inflammatory HCAs. Fifteen HCAs were HNF-1␣-inactivated. The corresponding lesions showed (1) diffuse signal dropout on T1-weighted chemical shift sequence due to steatosis, (2) isosignal or slight hypersignal on T2-weighted (T2W) images, and (3) moderate enhancement in the arterial phase, with no persistent enhancement in the portal venous and delayed phases. For the diagnosis of HNF-1␣-inactivated HCA, the positive predictive value of homogeneous signal dropout on chemical shift images was 100%, the negative predictive value was 94.7%, the sensitivity was 86.7%, and the specificity was 100%. Twenty-three HCAs were inflammatory and showed (1) an absence or only focal signal dropout on chemical shift sequence; (2) marked hypersignal on T2W sequences, with a stronger signal in the outer part of the lesions, correlating with sinusoidal dilatation areas; and (3) strong arterial enhancement, with persistent enhancement in the portal venous and delayed phases. Marked hypersignal on T2W sequences associated with delayed persistent enhancement had a positive predictive value of 88.5%, a negative predictive value of 84%, a sensitivity of 85.2%, and a specificity of 87.5% for the diagnosis of inflammatory HCA. Conclusion: HNF-1␣-mutated HCAs and inflammatory HCAs were associated with specific MRI patterns related to diffuse fat repartition and sinusoidal dilatation, respectively. (HEPATOLOGY 2008;48:808-818.) H epatocellular adenoma (HCA) is a rare type of benign monoclonal liver neoplasm, occurring mostly in young women using oral contraceptives. Several molecular features associated with HCA have recently been described (for review, see Rebouissou et al. 1 ).Biallelic-inactivating mutations of the TCF1 gene inactivating hepatocyte nuclear factor 1␣ (HNF-1␣) have been identified in 35% to 50% of HCAs. 2-4 Furthermore, HCAs harboring HNF-1␣ mutations have been shown to display repressed gluconeogenesis, together with activa-
Regardless of the FNH size or steatotic content, GS produced a similar and characteristic pattern and consequently represents a good marker for easily identifying resected FNH from other hepatocellular nodules.
Vascular tumors of the liver in adult patients include cavernous hemangioma, a common benign tumor; epithelioid hemangioendothelioma, a rare, usually low-grade malignant tumor; and angiosarcoma, a rare and very aggressive tumor. All these primary mesenchymal tumors develop on a normal liver and may also affect other organs. Their pathogenesis remains largely unknown. Hepatic tumors are increasingly detected incidentally due to widespread use of modern abdominal imaging techniques. Therefore, reliable noninvasive characterization and differentiation of such liver tumors is of major importance for clinical practice. Hemangioma follows a benign course, and a nonoperative approach for the majority of these lesions is recommended. A definitive diagnosis of epithelioid hemangioendothelioma and angiosarcoma requires histopathologic examination. Liver transplantation at an early stage has greatly improved the prognosis of epithelioid hemangioendothelioma. The prognosis of angiosarcoma remains dismal. Designing a worldwide database that contains all data about patients with these rare diseases is recommended.
Objectives Acoustic radiation force impulse (ARFI) technology represents an innovative method for the quantification of tissue elasticity. The aims of this study were to evaluate elasticity by ARFI in both liver tumors and background liver tissue and to compare ARFI measurements with histologic data in liver tumors and background liver. Methods Seventy‐nine tumors were prospectively studied: 43 benign and 36 malignant. Acoustic radiation force impulse measurements for each tumor type were expressed as mean ± standard deviation for both liver tumors and background liver; ARFI data were also correlated with histologic data. Results For liver tumors, the mean stiffness values were 1.90 ± 0.86 m/s for hepatocellular adenoma (n = 9), 2.14 ± 0.49 m/s for hemangioma (n = 15), 3.14 ± 0.63 m/s for focal nodular hyperplasia (n = 19), 2.4 ± 1.01 m/s for hepatocellular carcinoma (n = 24), and 3.0 ± 1.36 m/s for metastasis (n = 12). Important variations were observed within each tumor type or within a single tumor. These variations could have been due to necrosis, hemorrhage, or colloid. There was no statistically significant difference between the benign and malignant groups. Regarding background liver, it was possible to observe pathologic abnormalities in histologic analyses or liver function tests to explain the ARFI data. The degree of fibrosis was not the only determinant of liver stiffness in background liver; other factors such as portal embolization, sinusoidal obstruction syndrome caused by chemotherapy, and cholestasis, also could have interfered. Conclusions Acoustic radiation force impulse elastography could not allow differentiation between benign and malignant tumors. This study provides a better understanding of the correlation between ARFI and histologic data for both tumors and background liver.
Patients (85%) with hepatocellular adenoma (HCA) are women taking oral contraceptives. They can be divided into four subgroups according to their genotype/ phenotype features. (1) Hepatocyte nuclear factor 1a (HNF1a) biallelic somatic mutations are observed in 35% of the HCA cases. It occurs in almost all cases in women. HNF1a-mutated HCA are most of the time, highly steatotic, with a lack of expression of liver fatty acid binding protein (LFABP) in immunohistochemistry analyses. Adenomatosis is frequently detected in this context. An HNF1a germline mutation is observed in less than 5% of HCA cases and can be associated with MODY 3 diabetes. (2) An activating b-catenin mutation was found in 10% of HCA. These b-catenin activated HCAs are observed in men and women, and specific risk factors, such as male hormone administration or glycogenosis, are associated with their development. Immunohistochemistry studies show that these HCAs overexpress b-catenin (nuclear and cytoplasmic) and glutamine synthetase. This group of tumours has a higher risk of malignant transformation into hepatocellular carcinoma. (3) Inflammatory HCAs are observed in 40% of the cases, and they are most frequent in women but are also found in men. Lesions are characterised by inflammatory infiltrates, dystrophic arteries, sinusoidal dilatation and ductular reaction. They express serum amyloid A and C-reactive protein. In this group, GGT is frequently elevated, with a biological inflammatory syndrome present. Also, there are more overweight patients in this group. An additional 10% of inflammatory HCAs express b-catenin, and are also at risk of malignant transformation. (4) Currently, less than 10% of HCAs are unclassified. It is hoped that in the near future it will be possible with clinical, biological and imaging data to predict in which of the 2 major groups (HNF1a-mutated HCA and inflammatory HCA) the patient belongs and to propose better guidelines in terms of surveillance and treatment.
Radiologist sensitivity CTC for detection of polyps ≥ 6 mm in training was the sole independent predictor for subsequent sensitivity in detection of such polyps.
To assess the practical feasibility and effectiveness of real-time magnetic resonance (MR) temperature monitoring for the radiofrequency (RF) ablation of liver tumours in a clinical setting, nine patients (aged 49-87 years, five men and four women) with one malignant tumour (14-50 mm, eight hepatocellular carcinomas and one colorectal metastasis), were treated by 12-min RF ablation using a 1.5-T closed magnet for real-time temperature monitoring. The clinical monopolar RF device was filtered at 64 MHz to avoid electromagnetic interference. Real-time computation of thermal-dose (TD) maps, based on Sapareto and Dewey's equation, was studied to determine its ability to provide a clear end-point of the RF procedure. Absence of local recurrence on follow-up MR images obtained 45 days after the RF ablation was used to assess the apoptotic and necrotic prediction obtained by real-time TD maps. Seven out of nine tumours were completely ablated according to the real-time TD maps. Compared with 45-day follow-up MR images, TD maps accurately predicted two primary treatment failures, but were not relevant in the later progression of one case of secondary local tumour. The real-time TD concept is a feasible and promising monitoring method for the RF ablation of liver tumours.
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