The Early-Enhancing Hepatic Vein: Differentiating Focal Nodular Hyperplasia and Hepatic Adenoma With Pathologic Validation in MRI.

BACKGROUND: Focal nodular hyperplasia (FNH) and hepatic adenoma (HA) are two common benign liver lesions with different management options. In particular, resection is considered for large HA lesions to avoid possible bleeding complications or rarely malignant degeneration. PURPOSE: To determine whether early enhancement of a draining hepatic vein (EDHV) and absence of perilesional enhancement (PLE) on arterial phase MR images are useful for distinguishing FNH from HA. STUDY TYPE: Retrospective. POPULATION: A total of 34 patients: 16 with FNH and 18 with HA lesions. FIELD STRENGTH/SEQUENCE: A1.5 T, axial T1 fat-suppressed arterial postcontrast. ASSESMENT: Four abdominal radiologists blinded to pathologic diagnosis assessed for the presence or absence of EDHV in association with the lesion, definitively characterized by pathology. This was considered present if contrast could be identified in a hepatic vein contiguous with the lesion in question. Secondarily, PLE was evaluated. STATISTICAL TESTS: Fleiss's multirater kappa statistic, Chi-squared statistic, Phi-coefficient. Significance level P < 0.05. RESULTS: Considering all observations obtained from the four readers, an EDHV was identified with FNH 48.5% of the time. EDHV was seen with HA in 8.8% of cases. PLE was seen with significantly greater frequency in HA. The presence of an EDHV was associated with the absence of PLE. DATA CONCLUSION: In a lesion that may be either an FNH or HA, confident identification on arterial phase images of an EDHV should lead the reader to favor FNH, while the presence PLE should dissuade the reader from FNH. EVIDENCE LEVEL: 4. TECHNICAL EFFICACY: Stage 2.

Turner syndrome may be associated with hepatic adenoma.

Turner syndrome, caused by complete or partial loss of an X chromosome, is marked by a range of clinical manifestations including short stature, cardiovascular and renal disease. Hepatic involvement is an increasingly recognized concern. Steatosis and elevated transaminases are commonly observed in this population, but case reports have also described hepatic adenoma. Hepatic adenomas are rare, occurring in one per million people in the general population. They are typically benign but malignant transformation or rupture can occur. We sought to investigate whether Turner syndrome is associated with hepatic adenoma. Patients with Turner syndrome encountered at a single, academic institution between 2006 and 2020 were identified using ICD-10 codes and demographic, medication, laboratory, and imaging data were analyzed. Of the 228 patients identified, 46.9% had liver function testing, which were abnormal in 48.6%. Five of 77 patients with hepatic imaging had abnormalities. Three patients (1.3%) had hepatic adenoma, one after presenting in hemorrhagic shock due to rupture. These findings suggest that patients with Turner syndrome may have an increased risk for developing hepatic adenoma. Annual monitoring of liver function tests is already recommended in Turner syndrome. The addition of periodic hepatic imaging may also be beneficial.

Estrobolome and Hepatocellular Adenomas-Connecting the Dots of the Gut Microbial ß-Glucuronidase Pathway as a Metabolic Link.

Hepatocellular adenomas are benign endothelial tumors of the liver, mostly associated with female individual users of estrogen-containing medications. However, the precise factors underlying the selective development of hepatic adenomas in certain females remain elusive. Additionally, the conventional profile of individuals prone to hepatic adenoma is changing. Notably, male patients exhibit a higher risk of malignant progression of hepatocellular adenomas, and there are instances where hepatic adenomas have no identifiable cause. In this paper, we theorize the role of the human gastrointestinal microbiota, specifically, of bacterial species producing ß-glucuronidase enzymes, in the development of hepatic adenomas through the estrogen recycling pathway. Furthermore, we aim to address some of the existing gaps in our knowledge of pathophysiological pathways which are not yet subject to research or need to be studied further. As microbial ß-glucuronidases proteins recycle estrogen and facilitate the conversion of inactive estrogen into its active form, this process results in elevated levels of unbound plasmatic estrogen, leading to extended exposure to estrogen. We suggest that an imbalance in the estrobolome could contribute to sex hormone disease evolution and, consequently, to the advancement of hepatocellular adenomas, which are estrogen related.

Utilization of spectrins ßI and ßIII in diagnosis of hepatocellular carcinoma.

Spectrins are a group of cytoskeletal proteins which participate in many important cellular functions. It has been suggested that loss of spectrin isoforms may be associated with tumorigenesis of lymphoma, leukemia, gastric cancer and hepatocellular carcinoma (HCC). We recently reported that ßI spectrin expression was present in normal hepatocytes but lost in HCC cells, which suggested that spectrins may be helpful markers in diagnosis of HCC. In this study, using immunohistochemical staining, we further investigated the expression pattern of four spectrin isoforms (αII, ßI-III) on different benign and malignant liver tumors including focal nodular hyperplasia (FNH), hepatic adenoma (HA), HCC, and cholangiocarcinoma (CC). The results revealed that ßI spectrin was moderately to strongly positive in FNH and HA tissues, but was only weakly positive or lost in HCC cases and was weakly positive in all CC cases. In addition, the ßIII spectrin, majority of which was moderately positive in both FNH and HA tissues, was mostly lost in poorly differentiated HCC but remained at least moderately positive in most CC cases. These results suggest that spectrins ßI and ßIII may be used to differentiate well differentiated HCC from FNH or HA, and poorly differentiated HCC from CC, respectively.

Risk of hepatic neoplasms in Wolf-Hirschhorn syndrome (4p-): Four new cases and review of the literature.

Wolf-Hirschhorn syndrome (WHS) is a rare contiguous gene deletion disorder characterized by distinctive craniofacial features, prenatal/postnatal growth deficiency, intellectual disability, and seizures. Various malformations of internal organs are also seen. Neoplasia has not been documented as a typical feature of WHS. We review the three prior reports of hepatic neoplasia in WHS and add four previously unreported individuals. We propose that, in the context of the rarity of WHS, these seven cases suggest that hepatocellular neoplasia may be a feature of WHS.

Primary Liver Cancers-Part 1: Histopathology, Differential Diagnoses, and Risk Stratification.

Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) are the 2 most common primary malignant liver tumors, with hepatocellular and bile ductular differentiation, respectively. This article reviews the key histopathological findings of these 2 primary liver cancers and includes a review of the role of ancillary testing for differential diagnosis, risk stratification according to the American Joint Committee on Cancer (AJCC) staging recommendation, and a review of precancerous lesions. A literature review was conducted to identify articles with information relevant to precancerous precursors, current histopathological classification, ancillary testing, and risk stratification of primary malignant liver tumors. The histomorphology of normal liver, preinvasive precursors, primary malignancies, and morphological variants, and the utilization of ancillary tests for the pathological diagnosis are described. Dysplastic nodules are the preinvasive precursors of HCC, and intraductal papillary neoplasms of bile ducts and biliary intraepithelial neoplasia are the preinvasive precursors of CC. Benign liver nodules including focal nodular hyperplasia and adenomas are included in this review, since some forms of adenomas progress to HCC and often they have to be differentiated from well-differentiated HCC. A number of morphological variants of HCC have been described in the literature, and it is necessary to be aware of them in order to render the correct diagnosis. Risk stratification is still dependent on the AJCC staging system. The diagnosis of primary liver carcinomas is usually straightforward. Application of the appropriate ancillary studies aids in the differential diagnosis of difficult cases. The understanding of the carcinogenesis of these malignancies has improved with the standardization of the pathological classification of preinvasive precursors and studies of the molecular pathogenesis. Risk stratification still depends on pathological staging.

Hepatic Adenoma Arising in a Patient With Alagille Syndrome: A Case Report.

Alagille syndrome is associated with decreased bile ducts, cardiac abnormalities, vertebral body fusion defects, and a typical facies. While regenerative nodules and hepatocellular carcinoma have been described in these patients, hepatic adenoma has not. Herein, we present a patient with Alagille syndrome caused by a mutation in NOTCH2 with a hepatic adenoma. The clinical, imaging, and histologic features are discussed.

Diagnostic Value of Gadoxetic Acid-Enhanced MR Imaging to Distinguish HCA and Its Subtype from FNH: A Systematic Review.

Objective: The purpose of this study was to systematically review the diagnostic performance of gadoxetic acid-enhanced magnetic resonance imaging (Gd-EOB-DTPA-MRI) for differentiation of hepatocellular adenoma (HCA) and focal nodular hyperplasia (FNH), as well as HCA classification by using the low signal intensity (SI) in the hepatobiliary phase (HBP). Methods: A systematic process was used to review all published data in MEDLINE database about Gd-EOB-DTPA-MRI applied to differentiation of HCA and FNH, and classification of HCA by using low SI in the HBP. The pooled sensitivity and specificity were calculated to assess the diagnostic value of low SI in the HBP. Results: A review of 45 articles identified 10 eligible studies with a total of 288 HCA lesions. The pooled proportion of low SI in the HBP of HCA were 91% (95% CI: 0.81-0.97). In specific, the subtypes of HCA were 75% (95% CI: 0.64-0.85) for I-HCA, 100% (95% CI: 0.95-1.00) for H-HCA, 92% (95% CI: 0.70-1.00) for U-HCA, and 59% (95% CI: 0.00-1.00) for b-HCA, respectively. The pooled specificity and sensitivity of low SI in the HBP for distinguishing FNH from HCA were 95% (95% CI: 0.92-0.98) and 92% (95% CI: 0.87-0.96), respectively. Conclusion: Low SI in the HBP of Gd-EOB-DTPA-MRI is associated with higher accuracy for distinguishing HCA from FNH. However, the diagnostic accuracy may be overvalued, especially for the diagnosis of subtypes of b-HCA and I-HCA. Therefore, the risk factors and conventional imaging findings should be take into account simultaneously.

Extrahepatic metastasis of hepatocellular carcinoma arising from a hepatic adenoma without concurrent intrahepatic recurrence.

Hepatocellular carcinoma (hcc) arising from a hepatic adenoma is a rare phenomenon accounting for fewer than 5% of hcc cases; it seldom recurs after resection of the primary tumour. We report a case of extrahepatic metastasis of hcc arising from a hepatic adenoma that presented as a solitary sternal metastasis without any evidence of intrahepatic recurrence. Our patient was initially treated with radiation therapy and bland embolization, without response. Subsequently, the patient developed progressive disease while taking sorafenib. He later received chemotherapy with docetaxel and gemcitabine, with the development of multiple pulmonary and splenic nodules. However, he remained free of intrahepatic recurrence. To the best of our knowledge, this is the first case of extrahepatic metastasis of hcc arising from a hepatic adenoma without evidence of intrahepatic recurrence.

Safety and Outcomes of Percutaneous Biopsy of 61 Hepatic Adenomas.

OBJECTIVE: Given the recent classification of hepatic adenoma (HA) into subtypes and recognition of imperfect specificity of MRI to differentiate HA from focal nodular hyperplasia (FNH), there is a resurgent interest in the role of biopsy to diagnose HA. The purpose of this study was to determine the safety and outcomes of biopsy of HAs. MATERIALS AND METHODS: A retrospective review of the electronic medical records of all patients who underwent hepatic mass biopsy revealing HA from 2000 through 2013 was performed. The biopsy procedure parameters were evaluated. Complications were graded using the Common Terminology Criteria for Adverse Events. Pathology-specific outcomes related to the diagnosis of HA were assessed. RESULTS: Sixty patients (52 women and eight men) were identified with a mean age of 42 ± 13 (SD) years and a mean follow-up of 2.3 ± 3.0 years after biopsy. One patient had two HAs biopsied during the same procedure, resulting in a total of 61 biopsy-proven HAs. Of the 60 patients, one patient (2%) had a single major complication, which involved bleeding that resulted in a blood transfusion, and six patients (10%) had a minor complication. A total of six (10%) discordant biopsy results were found: Four biopsy-proven HAs (7%) revealed FNH on surgical resection or repeat biopsy, one HA (2%) showed well-differentiated hepatocellular carcinoma (HCC) at subsequent biopsy, and one HA (2%) showed findings suggestive of HCC on follow-up imaging. CONCLUSION: Complications after biopsy of HAs are uncommon. Although uncommon, discordant pathology results between biopsy and surgical resection may occur.

Intraoperative ultrasound for liver tumor resection in children.

BACKGROUND: Primary hepatic neoplasms in children are rare tumors. All malignant and medically refractive benign primary pediatric liver tumors ultimately require surgical resection for cure. Accurate preoperative imaging including multidetector helical computerized tomography or magnetic resonance imaging (MRI) is necessary to determine resectability. In the literature intraoperative ultrasound (IOUS) has proven to be a vital adjunct to liver surgery in adults, but this is not well established in children. MATERIALS AND METHODS: Between April 2003 and November 2014, children (<18-y-old) with a primary liver neoplasm, preoperatively evaluated with multidetector helical computerized tomography or MRI, who had IOUS used at the time of surgery were retrospectively reviewed. RESULTS: Preoperative evaluation with high-resolution MRI and IOUS were discordant in 4 of 19 patients (21%). In one case, right hepatic vein involvement was not accurately assessed with MRI. Two cases showed tumor involvement in segment IV by MRI; however, IOUS revealed no medial segment involvement. The final patient had a large (>5 cm), solitary hepatic adenoma on MRI, but IOUS in this case revealed diffuse adenomatosis. The operative management was altered in three of these cases. CONCLUSIONS: Although MRI can provide a detailed view of the hepatic anatomy and is an invaluable tool for preoperative planning for the pediatric patient with a primary liver neoplasm, IOUS may provide further and more up to date delineation of tumor extent and should be considered a crucial element in operative planning for hepatectomy in children.

Benign liver tumors in children: outcomes after resection.

PURPOSE: Benign liver tumors in children are rare and data regarding the surgical outcomes are deficient. We reviewed our experience in the management of these tumors particularly the extent, safety, and effectiveness of surgical resection. METHODS: Between March 2005 and March 2014, 10/90 liver resections were performed for benign liver tumors. Three other patients received conservative treatment. Demographic characteristics, operative management, morbidity, and mortality were analyzed. RESULTS: The median age of the patients was 12 months. The distribution of pathology was infantile hepatic hemangioendothelioma/hemangioma (n = 7), mesenchymal hamartoma (n = 4), adenoma (n = 1) and focal nodular hyperplasia (n = 1). Median tumor size was 12.25 cm (range 3.5-21 cm) with a median tumor volume of 576.64 cm(3) (range 13.9-1822.64 cm(3)). Non-anatomic resection was performed in 6/10 patients and the median blood loss was 100 ml (range 10-850 ml). Median length of hospital stay was 7 days (range 5-9 days). There were no mortality, none of the patients had a local recurrence, and all are alive at a median follow-up of 33 months. CONCLUSIONS: Two-third patients with benign liver tumors were managed with surgical excision, which comprised 11% of our resectional practice. Non-anatomical resection whenever feasible can be performed safely and does not compromise the oncological outcomes.

Liver masses: a clinical, radiologic, and pathologic perspective.

Liver masses present a relatively common clinical dilemma, particularly with the increasing use of various imaging modalities in the diagnosis of abdominal and other symptoms. The accurate and reliable determination of the nature of the liver mass is critical, not only to reassure individuals with benign lesions but also, and perhaps more importantly, to ensure that malignant lesions are diagnosed correctly. This avoids the devastating consequences of missed diagnosis and the delayed treatment of malignancy or the unnecessary treatment of benign lesions. With appropriate interpretation of the clinical history and physical examination, and the judicious use of laboratory and imaging studies, the majority of liver masses can be characterized noninvasively. Accurate characterization of liver masses by cross-sectional imaging is particularly dependent on an understanding of the unique phasic vascular perfusion of the liver and the characteristic behaviors of different lesions during multiphasic contrast imaging. When noninvasive characterization is indeterminate, a liver biopsy may be necessary for definitive diagnosis. Standard histologic examination usually is complemented by immunohistochemical analysis of protein biomarkers. Accurate diagnosis allows the appropriate selection of optimal management, which is frequently reassurance or intermittent follow-up evaluations for benign masses. For malignant lesions or those at risk of malignant transformation, management depends on the tumor staging, the functional status of the uninvolved liver, and technical surgical considerations. Unresectable metastatic masses require oncologic consultation and therapy. The efficient characterization and management of liver masses therefore requires a multidisciplinary collaboration between the gastroenterologist/hepatologist, radiologist, pathologist, hepatobiliary or transplant surgeon, and medical oncologist.

Robotic Left Hepatectomy for Hemorrhagic Hepatocellular Adenoma: The Role of Robotic Surgery in a Semi-Acute Setting.

Hepatocellular adenomas are benign liver tumors, more frequently seen in young women with a history of long-standing use of estrogenic hormonal contraception. An acute rupture of these adenomas can be the first sign of symptoms; however, they can be life-threatening. The definitive management of hepatic adenoma is liver resection for those larger than 4 cm as this cutoff size is known to be associated with an exponential risk of harboring malignancy and an increased risk for intratumor bleeding. Once intratumor hemorrhage occurs however, the management of hepatic adenoma becomes much more timely critical. In this study, we describe the use of robotic liver resection for the management of hemorrhagic hepatocellular adenoma in a semi-acute setting. We also include a series of robotic hepatic adenoma resection completed in our hepatobiliary program since 2016, which demonstrated the safety, feasibility, and reproducibility of robotic technique in treating hepatic adenoma.

A Case of a Beta-Catenin-Activated Hepatic Adenoma in a Male Patient With Familial Adenomatous Polyposis.

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.

Variation in the management of benign liver tumors: A European survey and case vignette study.

BACKGROUND: Management of focal nodular hyperplasia (FNH) and hepatocellular adenoma (HCA), is multidisciplinary and subject to practice variation. We aimed to evaluate variation in clinical management of FNH and HCA in Europe. METHODS: We distributed an online survey (November 2021-March 2022) among 294 European experts. The survey included questions on local practice and included eight clinical vignettes. The clinical vignettes focused on FNH or HCA management in the setting of sex, lifestyle modification, and pregnancy. RESULTS: The response rate was 32% and respondents included surgeons (38%), gastroenterologists/hepatologists (25%), radiologists (32%), and pathologists (1.6%) from ten European countries. We observed practice variation with regard to lifestyle modification and imaging follow-up in patients with FNH, and with regard to the management of HCA >5 cm before and during pregnancy. Finally, the management of HCA >5 cm after lifestyle modification deviated from EASL guideline recommendations. CONCLUSION: Our survey illustrates variability in FNH and HCA management in Europe. Several areas were identified for future research and guideline recommendations, including FNH follow-up and the management of HCA >5 cm. We propose the organization of Delphi consensus meetings to prioritize areas of research and update current guidelines to optimize management for all patients with benign liver tumors.

Fatal rupture of hepatic adenomatosis: Autopsy case and review of the literature.

Hepatic adenomatosis is a rare disease consisting of multiple adenomas in otherwise-normal liver parenchyma. Though the discovery of this entity goes back several years, its diagnosis is still challenging in terms of its definition and pathophysiology. Clinically, patients may be completely asymptomatic and the diagnosis is only made incidentally through imaging tests. The discovery could be made when complications occur such as intraperitoneal hemorrhage with hypovolemic shock due to the rupture of an adenoma. We report a fatal case of a ruptured adenoma in a case of hepatic adenomatosis discovered at autopsy. In order to achieve a better view of this disease, we conducted a literature review on this subject describing the pathogenesis, manifestations, and autopsy contribution to addressing this entity.

A Scoping Review of the Classification, Diagnosis, and Management of Hepatic Adenomas.

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 ß-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.