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.

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.

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.

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.

Hepatocellular adenomas (HCAs) are benign monoclonal liver tumors. Advances in molecular studies have led to the identification of distinct subtypes of HCA with unique pathways, clinical characteristics, and complication risks, underscoring the need for precise diagnosis and tailored management. Malignant transformation and bleeding remain significant concerns. Imaging plays a crucial role in the identification of these subtypes, offering a non-invasive method to guide clinical decision-making. Most studies involving patients with HCAs have been conducted in Western populations; however, the number of studies focused on Asian population has increased in recent years. HCAs exhibit distinct features in Asian population, such as a higher prevalence among male patients and specific subtypes (e.g., inflammatory HCAs). Current clinical guidelines are predominantly influenced by Western data, which may not fully capture these regional differences in epidemiology and subtype distribution. Therefore, this review presents the updated molecular classification of HCAs and their epidemiologic differences between Asian and Western populations, and discuss the role of imaging techniques, particularly magnetic resonance imaging using hepatobiliary contrast agents, in classifying the subtypes and predicting the risk of hepatocellular carcinoma.

Liver masses are common in children, however primary malignant neoplasms are rare, representing only 1% of all pediatric cancers. Hepatocellular neoplasms are the most common primary liver malignancies and hepatoblastoma (HB) is the most frequently diagnosed. The incidence of HB, which is increasing, is approximately of 2 cases per million in the United States, followed by hepatocellular carcinoma (HCC). Pediatric primary liver tumors of mesenchymal origin are less common, except for benign vascular tumors (hemangiomas). Malignant mesenchymal neoplasms represent approximately 10-15% of all, the most common being embryonal sarcoma and malignant rhabdoid tumor. Malignant vascular tumors are rare, but epithelioid hemangioendothelioma (EHE) and angiosarcoma can be seen in children. The development and adoption of consensus diagnostic, therapeutic and risk-stratifying approaches for pediatric patients with malignant liver tumors has been historically challenged by their rarity and by their diverse clinical and histological appearance. On-going collaborative efforts of international consortia including the Children's Oncology Group (COG) in North America, the German Society of Paediatric Oncology and Haematology (GPOH), the Societe Internationale d' Oncologie Pediatrique Liver Tumor Study Group (SIOPEL) in Europe and the Japanese Liver Tumor group (JPLT), have made significant contributions to understanding the clinical and histopathological features, as well as the underlying biology of pediatric liver tumors, in particular HB. A new classification of pediatric liver tumors drafted at the international consensus meeting held in Los Angeles, has been incorporated in the recent WHO classification and is currently used by the PHITT (Paediatric Hepatic Malignancy International Tumour Trial) and other therapeutic protocols. This manuscript provides an overview of salient diagnostic features and updates in classification and molecular characterization for the most common pediatric primary liver neoplasms. It also includes a brief overview of other less common but relevant tumors, which should be considered in the differential diagnosis.

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.

To assess the diagnostic performance of HBP MRI to discriminate β-HCA from other subtypes.

Systemic review and meta-analysis.

Ten original studies were included, yielding 266 patients with 397 HCAs (9%, 36/397 β-HCAs and 91%, 361/397 non-β-HCAs).

1.5 T and 3.0 T, HBP.

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.

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.

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.

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.

3 TECHNICAL EFFICACY: Stage 2.

Benign liver lesions are among the most commonly diagnosed abnormalities in liver imaging. They are often discovered incidentally during routine examinations or imaging conducted for unrelated reasons. These can be solid lesions, such as hemangiomas, focal nodular hyperplasia, hepatic adenomas, or cystic lesions. Recent advancements in MRI technology, particularly with hepatocyte-specific contrast agents, have enhanced the characterization of these lesions, reducing the reliance on invasive tissue sampling. Nevertheless, tissue sampling retains a crucial role in the evaluation of indeterminate lesions or those with malignant potential. While most benign liver lesions are asymptomatic, some can become symptomatic, causing discomfort, pain, or bleeding, particularly if the lesion is large. A deep understanding of the molecular underpinnings of the lesions is crucial for tailoring patient management strategies, particularly in distinguishing lesions that require surgical intervention from those that can be monitored. For instance, the molecular subclassification of hepatic adenomas has provided mechanistic insights and identified certain subtypes that are at higher risk of malignancy. Most benign liver lesions can be safely monitored; however, in patients with cirrhosis or a known primary malignancy, a high index of suspicion for cancer is required. It is crucial to carefully evaluate any liver lesion identified in these patients to ensure that indeterminate lesions are not overlooked. Effective management of benign liver lesions involves a multidisciplinary team, including hepatologists, surgeons, and radiologists, ensuring a comprehensive and individualized approach to patient care. This review outlines the clinical presentation of common benign liver lesions, providing a diagnostic and management framework. Emphasis is placed on a personalized approach to minimize patient distress and optimize outcomes by leveraging imaging advancements and multidisciplinary collaboration.

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.

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.

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.

Focal liver lesions (FLLs) have become an increasingly common finding on abdominal imaging, especially asymptomatic and incidental liver lesions. Gastroenterologists and hepatologists often see these patients in consultation and make recommendations for management of multiple types of liver lesions, including hepatocellular adenoma, focal nodular hyperplasia, hemangioma, and hepatic cystic lesions including polycystic liver disease. Malignancy is important to consider in the differential diagnosis of FLLs, and healthcare providers must be familiar with the diagnosis and management of FLLs. This American College of Gastroenterology practice guideline uses the best evidence available to make diagnosis and management recommendations for the most common FLLs.

Notably, the number of incidentally detected focal liver lesions (FLLs) has increased dramatically in recent years due to the increased use of radiological imaging. The diagnosis of FLLs can be made through a well-documented medical history, physical examination, laboratory tests, and appropriate imaging methods. Although benign FLLs are more common than malignant ones in adults, even in patients with primary malignancy, accurate diagnosis of incidental FLLs is of utmost clinical significance. In clinical practice, FLLs are frequently evaluated non-invasively using ultrasound (US), computed tomography (CT), and magnetic resonance imaging (MRI). Although US is a cost-effective and widely used imaging method, its diagnostic specificity and sensitivity for FLL characterization are limited. FLLs are primarily characterized by obtaining enhancement patterns through dynamic contrast-enhanced CT and MRI. MRI is a problem-solving method with high specificity and sensitivity, commonly used for the evaluation of FLLs that cannot be characterized by US or CT. Recent technical advancements in MRI, along with the use of hepatobiliary-specific MRI contrast agents, have significantly improved the success of FLL characterization and reduced unnecessary biopsies. The American College of Radiology (ACR) appropriateness criteria are evidence-based recommendations intended to assist clinicians in selecting the optimal imaging or treatment option for their patients. ACR Appropriateness Criteria Liver Lesion-Initial Characterization guideline provides recommendations for the imaging methods that should be used for the characterization of incidentally detected FLLs in various clinical scenarios. The American College of Gastroenterology (ACG) Clinical Guideline offers evidence-based recommendations for both the diagnosis and management of FLL. American Association for the Study of Liver Diseases (AASLD) Practice Guidance provides an approach to the diagnosis and management of patients with hepatocellular carcinoma. In this article, FLLs are reviewed with a comprehensive analysis of ACR Appropriateness Criteria, ACG Clinical Guideline, AASLD Practice Guidance, and current medical literature from peer-reviewed journals. The article includes a discussion of imaging methods used for the assessment of FLL, current recommended imaging techniques, innovations in liver imaging, contrast agents, imaging features of common nonmetastatic benign and malignant FLL, as well as current management recommendations.

Familial adenomatous polyposis (FAP) is an autosomal dominant syndrome caused by a germline mutation in the adenomatous polyposis coli (APC) gene, characterized by numerous colorectal adenomas. In addition, FAP patients may develop extraintestinal manifestations. Several cases of hepatocellular adenomas (HCA) detected accidentally in FAP patients have raised the so-far unsolved question of whether they represent a specific manifestation of FAP or a mere coincidence. To investigate the incidence of liver tumors in FAP patients, we analyzed our diagnostic database from 1991 to 2021. Among the 58 hepatic mass lesions identified, five HCAs occurring in three patients with FAP were identified, and comprehensive morphological, immunohistological, and molecular analysis employing targeted next-generation sequencing was conducted for characterization. The HCAs in this study showed no cytological or histological atypia. They displayed a diffuse, strong positivity for glutamine synthetase but no nuclear beta-catenin immunostaining. In two patients, the adenomas showed moderate immunoreactivity against serum amyloid A. Consistent with the diagnosis of FAP, molecular profiling revealed a pathogenic germline mutation of the APC gene in all analyzed adenomas as well as deleterious somatic second hits. All somatic mutations were localized between codons 1345 and 1577. No mutations were found in the catenin beta 1 gene. HCA in FAP patients can be a specific, although rare, neoplastic manifestation of this inborn disease and represents a distinct subgroup of HCAs. These benign tumors represent an important differential diagnosis for hepatic metastases in FAP patients and require adequate clinical and molecular (diagnostic) assessments for optimal patient guidance.

Although benign hepatocellular adenomas (HCA) are very rare, recent observations have shown their occurrence in patients with diabetes mellitus. Consequently, most of these cases are treated by resection due to concerns regarding their potential progression to hepatocarcinoma (HCC). This decision is largely driven by the limited number of studies on HCC subtyping and the lack of molecular and biological insights into the carcinogenic potential of benign tumors. This study aimed to comprehensively investigate the subtype classification of HCA and to compare and analyze gene expression profiling between HCA and HCC tissues. One fresh inflammatory HCA (I-HCA), three non-B non-C HCCs, two hepatitis B virus-HCCs, and one normal liver tissue sample were subjected to single-cell RNA sequencing (scRNA-seq). Comparative analysis of scRNA-seq among different tissues showed that phospholipase A2 group IIA (PLA2G2A) mRNA was specifically expressed in I-HCA, following RNA-seq analysis in formalin-fixed paraffin-embedded tissues from other HCAs. Immunohistochemistry using the PLA2G2A antibody in these tissues indicated that the positive reaction was mainly observed in hepatocytes of I-HCAs and stromal cells surrounding the tumor tissue in HCC were also stained. According to a clinical database, PLA2G2A expression in HCC does not correlate with poor prognosis. This finding may potentially help develop a new definition for I-HCA, resulting in a significant clinical contribution, but it requires validation with other fresh HCA samples.

We reported a notable case of inflammatory hepatocellular adenoma that grew during pregnancy, consequently changing its appearance on magnetic resonance imaging remarkably. A 5-months-pregnant 35-year-old woman presented with a 37-mm liver nodule that had been diagnosed as focal nodular hyperplasia 3 years earlier. She had never used oral contraceptives. After 2 months, the nodule grew to 57 mm. The patient delivered a full-term infant without complications. Gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging performed after delivery revealed markedly different findings compared with the first images. A liver biopsy was performed, and the tumor was diagnosed as inflammatory hepatocellular adenoma.

Nonalcoholic fatty liver disease (NAFLD) is characterized by excessive fat accumulation in the livers of patients without a history of alcohol abuse. It is classified as either simple steatosis (nonalcoholic fatty liver) or nonalcoholic steatohepatitis (NASH), which can progress to liver cirrhosis and hepatocellular carcinoma (HCC). Recently, it was suggested that the terms "metabolic dysfunction-associated steatotic liver disease (MASLD)" and "metabolic dysfunction-associated steatohepatitis (MASH)" should replace the terms "nonalcoholic fatty liver disease (NAFLD)" and "nonalcoholic steatohepatitis (NASH)", respectively, with small changes in the definitions. MASLD, a hepatic manifestation of metabolic syndrome, is rapidly increasing in incidence globally, and is becoming an increasingly important cause of HCC. Steatohepatitic HCC, a histological variant of HCC, is characterized by its morphological features resembling non-neoplastic steatohepatitis and is closely associated with underlying steatohepatitis and metabolic syndrome. Variations in genes including patatin-like phospholipase domain-containing protein 3 (PNPLA3), transmembrane 6 superfamily 2 (TM6SF2), and membrane-bound O-acyltransferase domain-containing protein 7 (MBOAT7) are associated with the natural history of MASLD, including HCC development. The mechanisms of HCC development in MASLD have not been fully elucidated; however, various factors, including lipotoxicity, inflammation, reactive oxygen species, insulin resistance, and alterations in the gut bacterial flora, are important in the pathogenesis of MASLD-associated HCC. Obesity and MASLD are also recognized as risk factors for hepatocellular adenomas, and recent meta-analyses have shown an association between MASLD and intrahepatic cholangiocarcinoma. In this review, we outline the pathology and pathogenesis of MASLD-associated liver tumors.

Current understanding and classification of pediatric hepatocellular adenomas (HCA) are largely based on adult data. HCAs are rare in children and, unlike in adults, are often seen in the context of syndromes or abnormal background liver. Attempts to apply the adult classification to pediatric tumors have led to several "unclassifiable" lesions. Although typically considered benign, few can show atypical features and those with beta-catenin mutations have a risk for malignant transformation. Small lesions can be monitored while larger (>5.0 cm) lesions are excised due to symptoms or risk of bleeding/rupture, etc. Management depends on gender, age, underlying liver disease, multifocality, size of lesion, histologic subtype and presence of mutation, if any. In this review, we summarize the data on pediatric HCAs and highlight our experience with their diagnosis and management.

Benign solid liver tumors are frequently discovered during routine sonographic examinations. As a rule, malignant tumors can be excluded using contrast medium-based sectional imaging; however, unclear cases can represent a diagnostic challenge. The category of solid benign liver tumors includes first and foremost hepatocellular adenoma (HCA), focal nodular hyperplasia (FNH) and hemangioma. Based on the most recent data, an overview of the current standards in the diagnostics and treatment is given.

Beyond oral contraceptives (OCs), metabolic factors have been suggested to increase the risk of hepatocellular adenoma (HCA). The impact of risks remains poorly defined, particularly among men and those with adenomatosis. Thus, we aimed to examine HCA clinical and outcome characteristics through a large multicenter cohort.

HCA diagnosis was made based on a combination of clinical, radiologic, and histologic criteria. Patient and clinical data including follow-up imaging, complications, and interventions were collected between 2004 and 2018 from 3 large academic centers.

Among 187 patients (163 female and 24 male) with HCA, 75 had solitary HCA, 58 had multiple HCAs, and 54 had adenomatosis. Over a median follow-up of 3.3 years (quartile 1: 1.2, quartile 3: 8.8), 34 patients (18%) had radiologic interventions, 41 (21%) had surgical resections, 10 (5%) developed tumoral hemorrhage, and 1 had malignant transformation. OC and corticosteroid use were present in 70% and 16%, respectively. Obesity (51%), type 2 diabetes (24%), hypertension (42%), and hypertriglyceridemia (21%) were also common. Metabolic comorbidities were more common in patients with large HCAs and adenomatosis. Compared with women, men had less hepatic steatosis (4% vs 27%), smaller HCAs (2.3 cm vs 4.4 cm), and more corticosteroid use (38% vs 11%) ( P < 0.05 for all). With OC cessation, 69% had a decrease in size of HCA, but 25% eventually required advanced interventions.

In this large HCA cohort, obesity and metabolic comorbidities were important risk factors associated with large HCAs and adenomatosis. Long-term adverse outcomes were infrequent, 5% had tumor hemorrhage, and 1 patient exhibited malignant transformation.

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.

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.

The medical ethical committee has approved the study protocol, patient information files and consent procedure and other study-related documents and procedures.

NL75014.078.20; Pre-results. https://www.trialregister.nl/trial/9092.

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.

Hepatocellular adenomas (HCA) rarely occur in males, and if so, are frequently associated with malignant transformation. Guidelines are based on small numbers of patients and advise resection of HCA in male patients, irrespective of size or subtype. This nationwide retrospective cohort study is the largest series of HCA in men correlating (immuno)histopathological and molecular findings with the clinical course.

Dutch male patients with available histological slides with a (differential) diagnosis of HCA between 2000 and 2017 were identified through the Dutch Pathology Registry (PALGA). Histopathology and immunohistochemistry according to international guidelines were revised by two expert hepatopathologists. Next generation sequencing (NGS) was performed to confirm hepatocellular carcinoma (HCC) and/or subtype HCA. Final pathological diagnosis was correlated with recurrence, metastasis and death.

A total of 66 patients from 26 centres fulfilling the inclusion criteria with a mean (±SD) age of 45.0 ± 21.6 years were included. The diagnosis was changed after expert revision and NGS in 33 of the 66 patients (50%). After a median follow-up of 9.6 years, tumour-related mortality of patients with accessible clinical data was 1/18 (5.6%) in HCA, 5/14 (35.7%) in uncertain HCA/HCC and 4/9 (44.4%) in the HCC groups (P = .031). Four B-catenin mutated HCA were identified using NGS, which were not yet identified by immunohistochemistry and expert revision.

Expert revision with relevant immunohistochemistry may help the challenging but prognostically relevant distinction between HCA and well-differentiated HCC in male patients. NGS may be more important to subtype HCA than indicated in present guidelines.

Our aim was to determine independent risk factors of clinical bleeding of hepatocellular adenoma (HCA) in order to define a better management strategy.

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.

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.

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.

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.

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.

Hepatocellular adenomas (HCAs) often pursue an innocuous clinical course. Recent work has elucidated important subtypes of HCA and biomarkers to identify them, including HCA at an increased risk for malignant transformation. Another key complication of HCAs is the risk of spontaneous tumoral hemorrhage, which may be life-threatening. Identification of a predictive biomarker for this clinical complication would therefore be of clinical value. It has been suggested that Argininosuccinate Synthase 1 (ASS1) immunohistochemistry (IHC) identifies HCA with a high propensity for hemorrhage. The aim of our study was to validate ASS1 IHC as a predictive marker of hemorrhage. Eighty-nine HCAs were collected for ASS1 IHC and subtyped according to published criteria. Clinical records were examined for evidence of tumoral hemorrhage. Twenty-one (23.6%) HCAs were complicated by clinically detected hemorrhage and were more likely to be resected (P=0.0002). Hemorrhage complicated all WHO subtypes of HCA. There was no association between hemorrhage and HCA subtype (P=0.92). Neither the distribution of ASS1 expression nor the intensity of ASS1 expression compared to normal liver showed a significant association with hemorrhage (P=0.051 and 0.34). Interlaboratory comparison of 8 cases showed good agreement regarding the intensity (6/8 and 7/8) and distribution of staining (7/8 and 7/8) across 3 laboratories performing ASS1 IHC. In conclusion, all subtypes of HCA may be complicated by hemorrhage. ASS1 IHC expression did not correlate with hemorrhagic complications. Caution is prudent before routine implementation of ASS1 IHC in clinical practice.

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.

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.

Due to the complexity of the disease, the treatment of HA is one the best examples of an individualized approach.

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.

A multi-institutional, retrospective review of patients with HA from 2008-2017 was performed. Patient demographics, disease characteristics, and clinical outcomes were analyzed.

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.

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.

Benign hepatic tumors (BHTs) are commonly detected as incidental finding mainly due to the frequent utilization of imaging modalities, including ultrasound (US), computed tomography (CT), and magnetic resonance imaging (MRI). Rigorous clinical evaluation, with a particular focus on chronic liver disease (CLD) or risk factors for CLD, medication history, physical examination for signs of CLD, blood tests, and a review of past liver radiology constitute the initial steps in the evaluation of a new liver lesion. Further, contrast-enhanced imaging using US, CT and MRI, can be used depending on the clinical scenario and their availability. The contrast-enhanced MRI provides detailed tissue assessment while avoiding exposure to radiations, although it is scarcely available and expensive. While the liver tissue-specific protocols ensure precise diagnosis, a biopsy is recommended in selected or doubtful cases. Further, most BHTs, such as hemangiomas, are harmless and do not require special management or followup, the hepatic adenomas and large or atypical cases of focal nodular hyperplasia are clinically relevant and require management/follow-up. In such cases, it is favorable to have a multidisciplinary team approach, which includes hepatologist, radiologist, hepatobiliary surgeon, and pathologist. This review aims to elaborate the current understanding of BHTs, and provide a practical guidance for primary care and practitioners of family and internal medicine for the disease evaluation and management.

Obesity and metabolic syndrome are increasingly recognized as risk factors for development of hepatocellular adenoma (HCA). The implications of weight loss on HCA regression has not been previously reviewed.

To analyze the effects of surgical and nonsurgical weight loss on HCA.

University Tertiary Hospital.

Literature review of full-text articles from PubMed and Scopus on patients with HCA who underwent surgical or nonsurgical weight loss was performed. Only English language articles were included and editorial comments were excluded. Wilcoxon signed rank test was used for paired data analysis. Spearman correlation was used for correlation between percent excess weight loss (%EWL) and number and size of HCA lesions.

Out of 4 studies, 7 patients were included in this review, all of whom were female. The median preintervention body mass index was 41 kg/m² compared with the postintervention body mass index of 28 kg/m² (P = .002). The %EWL following intervention positively correlated to reduction in number of HCA lesions (%) postintervention, with a Spearman correlation of .78 (P = .04). Similarly, %EWL postintervention was positively correlated, though not statistically significant, to reduction in lesion size (%), with a Spearman correlation of .46 (P = .29). All patients who were candidates for liver resection preintervention based on lesion size > 5 cm avoided liver resection postintervention following surgical and nonsurgical weight loss.

Effective long-term weight loss by surgical and nonsurgical methods result in regression of HCAs. Weight loss could avoid major liver resections or decrease the morbidity associated with liver surgery. Bariatric surgery should be considered as an option for management of surgically challenging HCAs in carefully selected obese patients. Multicenter long-term trials, while adjusting for cofounding factors, are required to determine the effects of surgical compared with nonsurgical weight loss on maintenance of HCA regression.

Focal nodular hyperplasia and hepatocellular adenoma are benign liver lesions that occur most frequently in women and may be found as incidental findings on imaging. hepatocellular adenomas may be infrequently associated with malignant progression or risk of rupture and as such, require surveillance or definitive treatments based on their size threshold. It is important clinically to differentiate these lesions, and utilizing imaging modalities such as contrast enhanced ultrasound or magnetic resonance imaging can be helpful in diagnosis. Further molecular subtyping of hepatocellular adenoma lesions may be beneficial to describe risk factors and potential future clinical complications.

A variety of conditions may mimic hepatic malignancy at MRI. These include benign hepatic tumors and tumor-like entities such as focal nodular hyperplasia-like lesions, hepatocellular adenoma, hepatic infections, inflammatory pseudotumor, vascular entities, and in the cirrhotic liver, confluent fibrosis, and hypertrophic pseudomass. These conditions demonstrate MRI features that overlap with hepatic malignancy, and can be challenging for radiologists to diagnose accurately. In this review we discuss the MRI manifestations of various conditions that mimic hepatic malignancy, and highlight features that may allow distinction from malignancy. Level of Evidence 5 Technical Efficacy Stage 3.

Hepatocellular adenoma (HCA) are benign liver tumours that may be complicated by haemorrhage or malignant transformation to hepatocellular carcinoma. Epidemiological data are fairly outdated, but it is likely to assume that the incidence has increased over the past decades as HCA are more often incidentally found due to the more widespread use of imaging techniques and the increased incidence of obesity. Various molecular subgroups have been described. Each of these molecular subgroups are defined by specific gene mutations and pathway activations. Additionally, they are all related to specific risk factors and show a various biological behaviour. These molecular subgroups may be identified using immunohistochemistry and molecular characterization. Contrast-enhanced MRI is the recommended imaging modality to analyse patients with suspected hepatocellular adenoma allowing to determine the subtype in up to 80%. Surgical resection remains to be the golden standard in treating HCA, although resection is deemed unnecessary in a large number of cases, as studies have shown that the majority of HCA will regress over time without complications such as haemorrhage or malignant transformation occurring. It is preferable to treat patients with suspected HCA in high volume centres with combined expertise of liver surgeons, hepatologists, radiologists and (molecular) pathologists.

New insights into molecular pathogenesis of hepatocellular adenomas (HCA) have allowed sub-classification based on distinct genetic alterations and a fresh look at characterizations of natural history. Clinically, this is important in understanding risk factors for two feared complications: malignant transformation and hemorrhage.

PubMed literature search for hepatocellular adenoma over all years, excluding case reports and articles focusing on multiple adenomas or adenomatosis.

The β-catenin exon 3 mutated HCA accounts for about 10% of all HCAs and is associated with the highest risk of malignant transformation. The HF1α subtype accounts for 30-40% of all HCAs and has the lowest risk of malignant transformation. Gender has also emerged as an increasingly important risk factor and males with HCA are at considerably higher risk of malignant transformation, regardless of tumor size. The increasing use of gadoxetic-enhanced MRI has allowed for improved differentiation of HCAs from focal nodular hyperplasia, as well as the identification of specific radiologic features of some subtypes, particularly the inflammatory and HF1α HCAs.

Classification of HCA by subtype has important implications for patient counseling and treatment given variable risks of malignant transformation and hemorrhage. Males and those with β-catenin exon 3 mutated HCAs are two groups who should always be counselled to undergo surgical resection. On the other hand, in the lower risk HF1α subtype observation is appropriate in lesions < 5 cm and may even be considered in larger lesions as longer follow-up data is aggregated and tumorigenesis is better understood.

The clinicopathologic features of hepatocellular adenoma in Asian populations have been poorly defined. The study aimed to characterize this rare entity in a single institution in Taiwan.

In total, 45 hepatocellular adenomas from 1995 to 2018 were included and sent for pathologic review and molecular subtyping.

The numbers of patients with hepatocellular adenoma has doubled in the recent decade. Surprisingly, men outnumbered women in our cohort (n = 26, 58% vs N = 19, 42%). A collection of clinical information revealed that overweight/obesity accounts for most of the associated conditions of hepatocellular adenoma. Only three women took oral contraceptives. There were 34 inflammatory (75%), three LFABP-negative (7%), four β-catenin activated (9%), and four unclassified (9%) hepatocellular adenomas. Ten inflammatory hepatocellular adenomas demonstrated strong and homogeneous glutamine synthetase staining and were thus also β-catenin activated. Notably, overweight and obesity were significantly associated with inflammatory hepatocellular adenoma than other subtypes (P = .029 and .056, respectively) and were strongly correlated with steatosis in background liver (P = .028 and.007, respectively). Malignant transformation (four borderline tumors and two hepatocellular carcinomas) was identified in six adenomas (two women and four men). All six hepatocellular adenomas with malignancy were β-catenin activated; β-catenin activation could serve as a biomarker for malignant progression.

The clinicopathologic features of hepatocellular adenoma in Taiwan are distinct from those reported in Western countries. Rare oral contraceptive usage and an emerging epidemic of overweight/obesity in Taiwan provides new insights into the pathogenesis of hepatocellular adenoma.

The presence of hepatocellular adenoma (HCA) in pregnant women requires special consideration, as it has been reported to carry the risk of growth and clinically significant haemorrhage. In this prospective study we assessed aspects of growth of HCA <5 cm during pregnancy.

This was a multicentre prospective cohort study in pregnant women with suspected HCA <5 cm on imaging. Definitive HCA diagnosis was established by MRI with hepatobiliary contrast agents (LCE-MRI), preferably before pregnancy. If at study inclusion a definitive diagnosis was lacking, LCE-MRI was performed after giving birth. Growth of the adenoma (defined as an increase of >20%) was closely monitored with ultrasound examinations throughout pregnancy.

Of the 66 women included, 18 were excluded from analysis because postpartum LCE-MRI did not confirm the diagnosis of HCA and showed the lesion to be focal nodular hyperplasia. The remaining 48 women, with an HCA confirmed by LCE-MRI, were followed during 51 pregnancies. Median age was 30 years (IQR 27-33) and median body mass index 31.9 kg/m² (IQR 26.3-36.6). Growth of HCA was seen in 13 of the pregnancies (25.5%); the median increase was 14 mm (IQR 8-19). One woman whose HCA grew to >70 mm successfully underwent transarterial embolization at week 26 of pregnancy to prevent further growth. The other 50 pregnancies proceeded without complications.

This study suggests that an HCA <5 cm confers minimal risk to a pregnant woman and none to her child. HCA increased in size during a quarter of pregnancies, so we recommend close monitoring with ultrasound examinations, enabling intervention if needed. In light of the large proportion of misdiagnosed HCA, LCE-MRI should be performed to prevent unnecessary anxiety in women with a benign liver lesion.

The presence of hepatocellular adenoma in pregnant women requires special consideration, as it carries the risk of growth and haemorrhage. In this study we followed 48 patients with hepatocellular adenoma <5 cm during 51 pregnancies and found that a hepatocellular adenoma during pregnancy confers minimal risk to the pregnant woman and none to her child.

Hepatocellular adenoma (HCA) is a rare liver tumor that has the potential for rupture and malignant transformation. Here, we report a case of multiple hepatocellular adenomas (HCAs) that were treated by surgical resection.

An 18-year-old man was admitted to our hospital with proteinuria. His height was 176.5 cm, weight was 126 kg, and body mass index was 40 kg/m². A liver tumor was incidentally found on abdominal ultrasonography. Contrast-enhanced computed tomography and gadoxetic acid-enhanced magnetic resonance imaging revealed three hepatic tumors that were 68 mm, 16 mm, and 9 mm in segments 3/4, 8, and 1, respectively. A percutaneous needle biopsy of the largest tumor was performed, the diagnosis of unclassified type HCA was made, and laparoscopic partial liver resection was performed of all three. The postoperative course was uneventful, and the patient was discharged 12 days later. An immunohistochemical examination revealed positivity for serum amyloid A protein, no decrease in fatty acid-binding protein, and negativity for β-catenin, glutamine synthetase, and cytokeratin 7. Therefore, these tumors were diagnosed as inflammatory type HCAs.

We reported an extremely rare case of multiple resected HCAs in a young, obese Japanese man. Our findings suggest that HCA should be considered in the differential diagnosis of liver tumor in obese patients. Further studies that consider clinical and molecular risk factors are required to establish individualized treatment plans for HCA in obese patients.

Stopping oral contraceptives following nodule detection usually prevents further hepatocellular growth (HCA); rare cases of growth have been reported after surgery. The aim of the study was to review our resected HCA cases and their outcomes and more specifically, growth.

We retrieved all HCA cases that required a second intervention and HCA growth cases of none resected HCA after resection of one or several HCAs.

Out of the 210 resected classified HCA cases, a second resection was performed in 5 cases, 4 of which were in women with HNF1alpha-inactivated adenomatosis (H-adenomatosis) and had a favorable outcome. The fifth case was the occurrence of an inflammatory HCA, 3 years after resection of a previous one. Of the 65 resected HNF1-inactivated HCAs (H-HCAs), the nodules that remained continued to increase very slowly in 3 adenomatosis cases. After surgery, the liver became dysmorphic years later in one case, and the nodules grew but not significantly in another case. After the diagnosis of adenomatosis, progressive growth leads to surgery 12 years later in the last case.

These results confirm that, in rare H-adenomatosis, size of nodules may increase very slowly, probably in part through coalescence of micro H-HCAs and leading occasionally to a second resection.

Two men (24 and 34 years of age) with a single hypervascular liver tumor were admitted to our hospital. The tumors were diagnosed as hepatocellular adenoma (HCA) by an ultrasound-guided biopsy and classified as inflammatory type by immunohistochemical staining. Considering the risk of malignant transformation, they underwent surgical resection. Although the serum levels of protein induced by vitamin K absence/antagonist-II (PIVKA-II) were slightly elevated, they normalized after the resection. The diagnosis of HCA including malignant transformation is often difficult by image findings alone. Careful immunohistochemical examinations are very useful for the diagnosis and classification of subgroups, including malignant transformation. In addition, we proved that HCA without malignant transformation expresses PIVKA-II.

OBJECTIVE. The purposes of this article are to discuss a variety of liver masses that can present with hemorrhage, including their characteristic imaging features, and to propose a diagnostic approach. CONCLUSION. A broad spectrum of pathologic conditions can present as spontaneous hemorrhage within or surrounding the liver and may present acutely or as a chronic or incidental finding. Imaging characteristics and clinical history can often narrow the differential diagnosis and guide management.

Hepatocellular adenoma (HCA) is a rare benign tumor and is related to the use of an oral contraceptive pill. Turner's syndrome requires various hormone replacement therapies, including the pill which is used as a female hormone replacement therapy. Herein we report a case of Turner's syndrome with HCA treated by liver segmentectomy.

A 36-year-old woman with Turner's syndrome was treated with oral contraceptive pills as a female hormone replacement therapy for 20 years. She presented with fatigue and liver tumor. Liver tumors in the posterior lobe measuring 60 mm and 10 mm in diameter were detected on CT; hence, she was referred to our department. Both the tumors showed high intensity in the arterial phase, iso-intensity in the portal and late phases, and low intensity in the hepatobiliary phase on Gb-EOB-MRI. She was diagnosed with multiple HCAs and underwent segmentectomy Section 7. Pathologically, both the tumors were diagnosed as HCAs, and inflammatory markers were detected by immunohistochemistry. Thirteen months postoperatively, she was doing well and there was no evidence of recurrence of HCA without the pill.

There is only one report of HCA in patients with TS (Espat et al., 2000). We reported a case of multiple HCAs in a patient with TS underwent hepatectomy.

With the use of the contraceptive pill as a long-term female hormone replacement therapy for Turner's syndrome, careful attention is required for HCA.

Hepatic adenomas (HAs) are a benign and relatively rare type of liver neoplasms. We review the diagnosis, evaluation, and potential therapeutic management options for patients with HA.

A comprehensive review of the English literature was performed utilizing MEDLINE/PubMed and Web of Science databases with end of search date the 30th April of 2018. In PubMed, the terms "hepatocellular," "hepatic," "liver," and "adenoma," "adenomatosis" were searched in the title and/or abstract.

Recent advances in molecular classification of HA have determined distinct subtypes with specific clinical, pathological, and imaging characteristics. In general, cessation of exogenous hormonal administration or weight loss may lead to HA regression. Surgical resection, either open or laparoscopic, should be considered in patients with symptoms and risk factors for hemorrhage or malignant transformation. These risk factors include tumor diameter greater than 5 cm, β-catenin activated subtype, and/or male gender. The management of acute hemorrhage should primarily aim at achieving hemodynamic stability via angioembolization followed by elective resection, whereas malignant transformation is treated according to oncologic resection principles. Although pregnancy is one of the known risk factors for tumor growth and associated complications, the presence of an HA per se should not be considered a contradiction to pregnancy.

Future genomic-based multicenter studies are required to provide a strong basis for formulating an evidence-based risk-adapted model that guides individualized management strategies for patients with HA.

Obesity and metabolic syndrome are increasingly recognized as risk factors for hepatocellular adenomas (HCA). There is still sparse evidence whether weight loss or bariatric surgery could induce HCA regression in these patients. In this brief report we describe the effect of weight loss on HCA regression in severe obese patients that had undergone bariatric surgery in our centre.

We performed an Electronic Patient Database search and included all patients who underwent bariatric surgery in our bariatric referral centre and had an ICD-10 code of benign neoplasm of liver in our centre from (2006-2017). All imaging studies of eligible patients were re-evaluated by the study radiologist. Primary outcome was change in maximal diameter of HCA.

Six of 11 eligible patients were excluded because their lesions were classified as probable focal nodular hyperplasia and two were lost to follow-up. Finally, three women with solitary (n = 1) or multiple HCA (n = 2) and a body mass index (BMI) ranging between 39 and 50 kg/m2 were included. In two patients, HCA completely regressed in 1-2 years following bariatric surgery, after BMI reductions of 36%-48%. The third patient showed a reduction of >50% in diameter of the largest HCA in 2.5 years after bariatric surgery (31% BMI reduction), with complete resolution of smaller HCA.

Bariatric induced weight loss results in significant regression of HCA in severe obese women, which emphasizes the role of overweight in HCA pathophysiology.

Hemorrhage is the main complication of hepatocellular adenoma (HCA). The aim of this study was to describe a single center's evolving management of patients with hemorrhagic HCA.

Between 1990 and 2013, all patients with hemorrhagic HCA were included. During the study period, the management evolved from urgent surgery (period <2004) to arterial embolization with (period, 2004-2010) or without (period > 2010) delayed resection.

A total of 56 patients were identified. The median (range) size of HCA and the hematoma was 80 mm (35-160) and 50 mm (10-160). Patients were treated by urgent resection (group 1, n = 6), delayed resection with or without embolization (group 2, n = 43) and systematic embolization without surgery (group 3, n = 7). Embolization was performed in 0/6, 15/43 and 7/7 in groups 1, 2 and 3. Urgent resection was associated with higher morbidity (p < 0.001). Complete necrosis was observed in 0/6, 13/43 and 3/7 patients, and on histology it was associated with embolization (p = 0.001), a hematoma-tumor ratio > 60% (p = 0.046) and a cystic non-viable lesion before surgery (p < 0.001).

Hemodynamic stability can be achieved in patients presenting with hemorrhagic HCA by none surgical means. Subsequent surgery can be completely avoided with such an approach in up to 40% of patients.

Hepatocellular adenomas are benign liver lesions with a risk of rupture and malignant transformation. Various molecular subgroups have been identified which appear to have characteristic morphological and immunohistochemical features. We examined the morphology and immunohistochemical profile of a series of 121 HCA from 97 patients to identify the HCA subtypes present and determine the number at risk for malignant transformation according to the World Health Organization (WHO) criteria for hepatocellular adenomas. There were 34 HNF1α inactivated HCA (28%), 61 inflammatory HCA (50%), 15 β-catenin activated HCA (12%) and 11 unclassified adenomas (9%). This proportion of cases was similar to that seen in other series utilising molecular classification. The morphological features of the adenomas were suggestive but not definite indicators of the subtypes present. Morphological features that showed overlap between the subtypes included steatosis within the lesion, a ductular reaction and focal atypia, so that immunohistochemical typing was required for accurate classification. In conclusion, immunohistochemistry is a clinically useful surrogate for identifying underlying molecular changes in the HCA subtypes.

It is rare but not uncommon to discover micro/small HNF1α-inactivated hepatocellular adenoma (H-HCA) outside the context of resected H-HCA. We aimed to review our cases of micro/small H-HCA discovered by chance on different kinds of liver resected specimens.

We retrieved cases of micro/small H-HCA discovered by chance on resected specimens outside the context of H-HCA. All these nodules were liver fatty acid binding protein (LFABP)-negative contrasting with normal positivity in the surrounding non-tumoural liver, ruling out the possibility of focal steatosis or other subtypes of micro-HCAs.

We identified 19 micro/small H-HCA cases. In 16 cases they were discovered in patients who underwent surgery for benign nodules including one haemangioma, six focal nodular hyperplasia, seven inflammatory HCA (including one with b-catenin activation), one HCA, whose subtype could not be identified because of massive necrosis/hemorrhage, and one hepatocellular carcinoma. In two additional cases, patients followed up for a melanoma underwent liver surgery to remove micro nodules possibly related to a metastatic process. Finally in one case a micro nodule was seen and resected during a cholecystectomy.

Taken together, H-HCAs are more frequent than we initially supposed as micro and small HCAs cannot all be detected by routine ultrasound. Despite no information on the potential growth of these micro/small H-HCAs, there is no argument to stop oral contraceptives or to ask for a specific regular surveillance. The association of different subtypes of HCAs with focal nodular hyperplasia suggests they share or have common etiological factors.

A 32-year-old Japanese woman was admitted to our hospital for the diagnosis and treatment of multiple liver tumors. She had been receiving 125 mg testosterone enanthate every 2 weeks following female-to-male gender identity disorder (GID) diagnosis at 20 years of age. Ultrasonography, computed tomography, and magnetic resonance imaging showed 11 hepatic nodular tumors with a maximum diameter of 28 mm. Liver tumors with hepatocellular adenoma (HCA) were diagnosed with needle biopsy. Segmentectomy of the left lateral lobe including two lesions, subsegmentectomy of S6 including two lesions, enucleation of each tumor in S5 and S7, and open surgical radiofrequency ablation for each tumor in S4 and S7 were performed. Immunohistochemical specimens showed that the tumor cells were diffusely and strongly positive for glutamine synthetase and that the nuclei were ectopically positive for β-catenin. Thus, the tumors were diagnosed as β-catenin-activated HCA (b-HCA). Transcatheter arterial chemoembolization plus subsequent radiofrequency ablation was performed for the 3 residual lesions in S4 and S8. Although testosterone enanthate was being continued for GID, no recurrence was observed until at least 22 months after the intensive treatments. HCA development in such patients receiving testosterone should be closely monitored using image inspection.