Dynamic Contrast Enhanced-MRI and Apparent Diffusion Coefficient Quantitation for Differentiate Hepatocellular Carcinoma from Hepatocellular Adenoma.

BACKGROUND: Due to their overlapping radiological characteristics, hepatic lesions, such as hepatocellular carcinoma (HCC) and hepatocellular adenoma (HCA), present a substantial diagnostic challenge. Accurate differentiation between HCC and HCA is essential for the best clinical treatment and therapeutic decision-making. This study aims to assess the potential role of DCE-MRI and Apparent Diffusion Coefficient (ADC) quantitation in the diagnosis of hepatocellular carcinoma (HCC) from hepatocellular adenoma (HCA). METHODS: 103 patients (56 HCC, 47 HCA) with histopathologically proven hepatocellular lesions were the subjects of a cross-sectional investigation. A standardized imaging technique was used for DCE-MRI on all patients. Diffusion-weighted imaging (DWI) provided the ADC values. The diagnostic efficacy of DCE-MRI and ADC in differentiation was evaluated using statistical analyses, such as t-tests and receiver operating characteristic (ROC) curve analysis. SPSS VER 16 was used for the analysis of the collected data. RESULTS: A total of 103 patients (female: male= 52:51, 57.14±3.09 years) were included in the study. The study revealed significant differences in DCE-MRI parameters and ADC values between HCC and HCA lesions. ADC value was significantly lower in HCC than in HCA (p < 0.001). The area under the curve (AUC) was 0.78 (95% CI: 0.69-0.87) for ADC, 0.84 (95% CI: 0.76-0.91) for Ktrans, and 0.72 (95% CI: 0.62-0.82) for Ve. Sensitivity and specificity for ADC were 76.59% and 71.42%, respectively. Also, PPV and NPV of ADC were 69.23% and 78.43%, respectively. Sensitivity and specificity for Ktrans were 82.14% and 76.59%, respectively. Also, PPV and NPV of Ktrans were 80.7% and 78.26%, respectively. CONCLUSION: In conclusion, DCE-MRI-derived parameters, along with ADC values, exhibit promise as non-invasive tools for differentiating HCC from HCA.

To assess the quantitative features of focal liver lesions in gadoxetic acid enhanced MRI and to determine whether these features can accurately differentiate benign form malignant lesions.

PURPOSE: The study aims at assessing the quantitative features which distinguish focal liver lesions (FLLs) in gadoxetic acid (GA) enhanced liver MRI and at determining whether these features can accurately differentiate benign from malignant lesions. MATERIAL AND METHODS: 107 patients with 180 unequivocal FLLs in previous examinations were included in a single-center retrospective study. All patients underwent a MRI test of the liver with GA. 99 benign and 74 malignant lesions were included. The group of benign lesions consisted of 60 focal nodular hyperplasias (FNH), 22 hemangiomas (HMG), 6 hepatic adenomas (HA), and 11 other benign lesions (1 angiomyolipioma, 6 lesions histopathology diagnoses as benign without further specification, or ones lacking features of malignancy, and 4 lesions radiologically diagnosed as benign which remained stable in the follow-up studies). The group of malignant lesions consisted of primary 51 hepatocellular carcinomas, 12 metastases, and 11 metastases from melanoma malignum (MM meta). 7 FLLs were excluded (4 cases of uncertain histopathological diagnosis, 2 cholangiocarcinomas, and 1 regenerative nodule). For the included lesions ROI (region of interest) measurements were taken by two observers in the T2-w, ADC (apparent diffusion coefficient) and in the T1-w sequence in the hepatobiliary phase (HBP). The interobserver agreement was evaluated with the Wilcoxon test. The Kruskal - Wallis, Mann - Whitney U and post hoc Dunn's tests were applied to assess if there were any significant differences in the ROI values between individual lesions. The variables with the p values of < 0.05 were considered statistically significant. RESULTS: We found significant differences in the ROI values between lesions with p < 0.0001. Strikingly high ROI values in the T2-w sequence were found for HMG. The lowest ADC values were encountered for metastases and MM metastases. The highest ROI values in the HBP were found for FNH, and the lowest for metastases. We also found statistically significant differences in the ROI values between benign and malignant lesions with benign lesions presenting statistically higher ROI values compared to malignant lesions. CONCLUSIONS: There were significant differences in the ROI values among different types of FLLs. The predominant quantitative feature in the T2-w sequence was a strikingly high ROI value for HMG. Benign lesions presented statistically higher ROI values in the T2-w, ADC, and HBP sequences compared to malignant lesions. This was true for all lesions except for HA.

Two-year dermal carcinogenicity bioassay of triclosan in B6C3F1 mice.

Triclosan is a widely used antimicrobial agent in personal care products, household items, medical devices, and clinical settings. Due to its extensive use, there is potential for humans in all age groups to receive lifetime exposures to triclosan, yet data on the chronic dermal toxicity/carcinogenicity of triclosan are still lacking. We evaluated the toxicity/carcinogenicity of triclosan administered dermally to B6C3F1 mice for 104 weeks. Groups of 48 male and 48 female B6C3F1 mice received dermal applications of 0, 1.25, 2.7, 5.8, or 12.5 mg triclosan/kg body weight (bw)/day in 95% ethanol, 7 days/week for 104 weeks. Vehicle control animals received 95% ethanol only; untreated, naïve control mice did not receive any treatment. There were no significant differences in survival among the groups. The highest dose of triclosan significantly decreased the body weight of mice in both sexes, but the decrease was ≤ 9%. Minimal-to-mild epidermal hyperplasia, suppurative inflammation (males only), and ulceration (males only) were observed at the application site in the treated groups, with the highest incidence occurring in the 12.5 mg triclosan/kg bw/day group. No tumors were identified at the application site. Female mice had a positive trend in the incidence of pancreatic islet adenoma. In male mice, there were positive trends in the incidences of hepatocellular carcinoma and hepatocellular adenoma or carcinoma (combined), with the increase of carcinoma being significant in the 5.8 and 12.5 mg/kg/day groups and the increase in hepatocellular adenoma or carcinoma (combined) being significant in the 2.7, 5.8, and 12.5 mg/kg/day groups.

Key CT and MRI findings of drug-associated hepatobiliary and pancreatic disorders.

Obtaining an imaging diagnosis of various hepatobiliary and pancreatic disorders caused by certain drugs can often be challenging. Familiarity with these conditions may improve diagnostic accuracy and patient management. This review aimed to describe the imaging findings of drug-associated hepatobiliary and pancreatic disorders and identify suggestions for obtaining a correct diagnosis. We focused on relatively common disorders or those that can present with characteristic imaging findings, such as drug-induced acute hepatitis, sinusoidal obstruction syndrome, focal nodular hyperplasia-like lesions, hepatocellular adenoma, pseudocirrhosis, chemotherapy-associated steatohepatitis, amiodarone deposition in the liver, secondary iron overload, drug-induced pancreatitis, pancreatic enlargement after epoprostenol therapy, ceftriaxone-associated gallbladder pseudolithiasis, immune-related adverse events, and methotrexate-associated lymphoproliferative disorders.

Association Between Gadoxetic Acid-Enhanced Magnetic Resonance Imaging, Organic Anion Transporters, and Farnesoid X Receptor in Benign Focal Liver Lesions.

The organic anion uptake and efflux transporters [organic anion-transporting polypeptide (OATP)1B1, OATP1B3 and multidrug resistance-associated protein (MRP)2 and MRP3] that mediate the transport of the hepatobiliary-specific contrast agent gadoxetate (Gd-EOB-DTPA) are direct or indirect targets of the farnesoid X receptor (FXR), a key regulator of bile acid and lipid homeostasis. In benign liver tumors, FXR expression and activation is not yet characterized. We investigated the expression and activation of FXR and its targets in hepatocellular adenoma (HCA) and focal nodular hyperplasia (FNH) and their correlation with Gd-EOB-DTPA-enhanced magnetic resonance imaging (MRI). Gd-EOB-DTPA MRI patterns were assessed by an expert radiologist. The intensity of the lesions on the hepatobiliary phase was correlated to mRNA expression levels of OATP1B1, OATP1B3, MRP2, MRP3, FXR, and small heterodimer partner (SHP) in fresh surgical specimens of patients with FNH or HCA subtypes. Normal and tumor sample pairs of 43 HCA and 14 FNH were included. All FNH (14/14) were hyperintense. Of the 34 HCA with available Gd-EOB-DTPA-enhanced MRI, 6 were hyperintense and 28 HCA were hypointense. OATP1B3 was downregulated in the hypointense tumors compared with normal surrounding liver tissue (2.77±3.59 vs. 12.9±15.6, P < 0.001). A significant positive correlation between FXR expression and activation and OATP1B3 expression level was found in the HCA cohort. SHP showed a trend toward downregulation in hypointense HCA. In conclusion, this study suggests that the MRI relative signal in HCA may reflect expression level and/or activity of SHP and FXR. Moreover, our data confirms the pivotal role of OATP1B3 in Gd-EOB-DTPA uptake in HCA. SIGNIFICANCE STATEMENT: FXR represents a valuable target for the treatment of liver disease and metabolic syndrome. Currently, two molecules, ursodeoxycholate and obeticholate, are approved for the treatment of primary biliary cirrhosis and cholestasis, with several compounds in clinical trials for the treatment of metabolic dysfunction-associated fatty liver disease. Because FXR expression and activation is associated with gadoxetate accumulation in HCA, an atypical gadoxetate-enhanced MRI pattern might arise in patients under FXR-targeted therapy, thereby complicating the differential diagnosis.

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.

Focal nodular hyperplasia-like nodules arising in the setting of hepatic vascular disorders with portosystemic shunting show ß-catenin activation.

Hepatocellular nodules can develop in the setting of chronic hepatic vascular disorders including those characterized by portosystemic shunts such as Abernethy malformation and post-Fontan procedure. The nodules can range from benign lesions such as regenerative nodules, focal nodular hyperplasia (FNH), and hepatocellular adenoma (HCA) to malignant neoplasms such as hepatocellular carcinoma (HCC). In many instances, these nodules are difficult to place into well-defined categories based on radiologic or histologic features. Nodular lesions that resemble FNH are common in this context and have been described as FNH-like nodules, the nature of which is not well-established. This study examines 6 liver resections from patients with vascular disease characterized by portosystemic shunts. A wide range of nodules were present in these cases, including regenerative nodules (n = 2), FNH and FNH-like (n = 30), HCA (n = 10), HCA-like (n = 13), and HCC (n = 2). Six nodules from 3 patients were categorized as FNH-like due to one or more features such as nodular architecture, fibrous septa, and ductular reaction, but lack of typical map-like glutamine synthetase (GS) staining. Further characterization of these 6 FNH-like nodules showed diffuse GS staining in all nodules (3 diffuse homogeneous, 3 diffuse heterogeneous). Targeted next-generation sequencing identified CTNNB1 alterations in all tested FNH-like nodules (n = 4). These results indicate that FNH-like nodules in the setting of chronic hepatic vascular disorders can be neoplastic. Since the presence of ß-catenin activation portends a potential risk for malignant progression, GS and ß-catenin immunohistochemistry should be obtained in all cases showing FNH-like morphology, with molecular analysis performed in cases with indeterminate staining pattern.

CRP Versus SAA for Identification of Inflammatory Hepatic Adenomas.

Subtyping hepatic adenomas is important for patient management due to differing complication risks. Immunohistochemical staining with C-reactive protein (CRP) and serum amyloid-A (SAA) is widely accepted as a surrogate for molecular classification to identify inflammatory hepatocellular adenomas. Limited data, however, has been published on how these 2 stains compare for sensitivity. We conducted a large, multicenter, retrospective study to examine the sensitivity and staining characteristics of CRP and SAA in inflammatory hepatic adenomas, with focal nodular hyperplasia (FNHs) as a control group. Inflammatory adenomas were identified in 133 patients (average age 37 years, 109 were female). In all, 69.9% of cases were resection specimens and 90.2% of all cases showed positive staining for both CRP and SAA; 10 (7.5%) were positive for CRP only and 3 (2.3%) were positive for SAA only. CRP was more sensitive than SAA (97.74% vs. 92.48%, P -value = 0.0961) and showed more extensive and intense staining, with a significantly higher modified H-score ( P <0.001). Focal nodular hyperplasia can also show positive CRP and SAA staining but with a lower modified H-score ( P <0.0001). Based on beta-catenin and glutamine synthetase staining, 26 of inflammatory adenomas also had beta-catenin activation (19.5%). All 3 cases with positive SAA and negative CRP staining were beta-catenin activated. In contrast, the proportion of cases that were CRP positive and SAA negative was similar regardless of beta-catenin activation. The data affirms the strategy of using both CRP and SAA immunostains for hepatic adenoma subtyping and raises the awareness of the highly variable nature of SAA staining characteristics.

Surgical indications for solid hepatic benign tumors: An updated literature review.

Hepatic hemangioma, focal nodular hyperplasia, and hepatic adenoma are the most common benign solid liver tumors. However, their surgical indications have been the subject of debate. Minimally invasive liver resection reduces the cost of surgery and may lead to overtreatment of benign liver tumors. Recently, there has been a growing understanding of the etiology, pathogenesis, and natural history of these tumors. Great progress has also been made in imaging. The use of MRI and contrast agents has improved the accuracy of non-invasive diagnosis of these tumors, and especially in the identification of specific molecular subtypes of liver adenoma. These factors have resulted in alterations of surgical indications for these tumors. This article examines recent literature and it discusses the surgical indications for hepatic hemangioma, focal nodular hyperplasia, and hepatic adenoma while summarizing modifications in clinical management.

Hepatic adenoma in a 7-year-old girl: a case report and literature review.

BACKGROUND: Hepatocellular adenomas (HCAs) are rare benign tumors of the liver that occur predominantly in women taking oral contraceptives. In children, HCAs comprise < 5% of hepatic tumors. We report a case of HCAs in a 7-year-old girl with estrogen and glucose imbalance. CASE PRESENTATION: A 7-year-old girl was presented to our hospital with bilateral breast enlargement for 2 months, polydipsia, polyuria, polyphagia, hyperglycemia, and significant weight gain. Computed tomography (CT) showed a 7.2 cm×6.9 cm×5.3 cm round-shaped mass in the left inner lobe of the liver, ovarian ultrasound showed multiple follicles in the ovaries bilaterally, and cranial magnetic resonance imaging (MRI) showed an enlarged superior pituitary. Hematological and biochemical results were as follows: fasting glucose was 19.7 mmol/L, estradiol was 122.9 pmol/L, follicle-stimulating hormone 10.81 IU/L, luteinizing hormone 10.99 IU/L, insulin-like growth factor 1,513 ng/mL, glutamine aminotransferase 86 U/L, and alkaline phosphatase 362 U/L. Thyroid functions, methemoglobin, fetal protein, carcinoembryonic antigen, and chorionic gonadotropin were normal. The patient had a complete surgical resection of the liver tumor, and the postoperative histopathological diagnosis was HCAs. After the surgery, insulin was injected and the glucose levels were stable. During the 36-month follow-up period, neither tumor recurrence nor significant abnormalities were detected using color Doppler ultrasound of the liver. The child's precocious puberty is currently under control. CONCLUSIONS: HCAs are particularly rare in children with liver tumors, and risk factors for the development of HCAs in children include sex hormone imbalance, obesity, Fanconi anemia (FA), glycogen storage diseases (GSDs) type I, III, and IV, galactosemia, immunodeficiency, congenital portosystemic shunts (CPSS), cardiac hepatopathy status-post Fontan procedure, Hurler syndrome, familial adenomatous polyposis, germline HNF1A mutations, and maturity-onset diabetes of the young type 3. Most HCAs are detected during a physical examination without clinical symptoms, and some patients may present with symptoms such as abdominal pain, abdominal distension, and abdominal masse. Serum liver function tests can show increased alkaline phosphatase (ALP) and γ- glutamyl transferase (GT), whereas α-Fetoprofein (AFP) levels are normal. The definitive diagnosis relies mainly on histopathological examination. Because HCAs can rupture and bleed and become malignant. Early surgical treatment is recommended after detection.

Evaluating Liver Biopsies with Well-Differentiated Hepatocellular Lesions.

Needle core biopsies of liver lesions can be challenging, particularly in cases with limited material. The differential diagnosis for well-differentiated hepatocellular lesions includes focal nodular hyperplasia, hepatocellular adenoma, and well-differentiated hepatocellular carcinoma (HCC) in noncirrhotic liver, while dysplastic nodules and well-differentiated HCC are the primary considerations in cirrhotic liver. The first part of this review focuses on histochemical and immunohistochemical stains as well as molecular assays that are useful in the differential diagnosis. The second portion describes the features of hepatocellular adenoma subtypes and focuses on the differential diagnoses in commonly encountered clinicopathologic scenarios.

Thromboelastographic results and hypercoagulability in dogs with surgically treated hepatocellular adenoma and carcinoma: A Veterinary Society of Surgical Oncology prospective study.

BACKGROUND: The most common haemostatic abnormality in dogs with cancer is hypercoagulability. A transient hypercoagulability has been documented in people with hepatocellular carcinoma (HCC) that resolves within weeks following hepatic tumour resection. OBJECTIVE: The objective was to compare the haemostatic status of dogs with liver tumours and healthy control dogs, by comparing coagulation and thromboelastography (TEG) measurements at three time points. METHODS: Liver tumour and healthy control dogs receiving surgery for liver lobectomy and ovariohysterectomy, respectively, were prospectively enrolled. All dogs had blood collected at three time points: pre-operative, 24 h post-operative and ~2 weeks post-operative. Haematological and haemostatic values were compared across time points in each group using repeated measures ANOVA tests. RESULTS: Ten and eight dogs were enrolled for the liver and control groups, respectively. Platelet count was significantly higher in the liver group than the control group at all time points, but within the normal range (pre-operative: 438.7 vs. 300.9 × 109 /L, p = .0078; 24 h post-operative: 416.2 vs. 283.9 × 109 /L, p = .0123; 10-14 days post-operative: 524.6 vs. 317.3 × 109 /L, p = .0072). The measure of the overall coagulant state (G-value) was significantly increased for the liver group compared to the control group at all time points (pre-operative: 15.6 vs. 8.6 d/sc, p = .0003; 24 h post-operative: 18.3 vs. 11.2 d/sc, p = .039; 10-14 days post-operative: 15.1 vs. 9.6 d/sc, p = .015). CONCLUSION: The liver group was hypercoagulable based on elevated G-values at all time points compared to the control group. This hypercoagulability was attributed to the effect of hepatic tumours alone, and not secondary to surgery and anaesthesia.

Bleeding hepatocellular adenoma: historical series and outcomes.

INTRODUCTION: hepatocellular adenoma - AHC - is a rare benign neoplasm of the liver more prevalent in women at reproductive age and its main complication is hemorrhage. In the literature, case series addressing this complication are limited. METHODS: between 2010 and 2022, 12 cases of bleeding AHC were attended in a high-complexity university hospital in southern Brazil, whose medical records were retrospectively evaluated. RESULTS: all patients were female, with a mean age of 32 years and a BMI of 33kg/m2. The use of oral contraceptives was identified in half of the sample and also half of the patients had a single lesion. The mean diameter of the largest lesion was 9.60cm and the largest lesion was responsible for bleeding in all cases. The presence of hemoperitoneum was documented in 33% of the patients and their age was significantly higher than the patients who did not have hemoperitoneum - 38 vs 30 years, respectively. Surgical resection of the bleeding lesion was performed in 50% of the patients and the median number of days between bleeding and resection was 27 days. In only one case, embolization was used. The relation between ingrowth of the lesions and the time, in months, was not obtained in this study. CONCLUSION: it is concluded that the bleeding AHC of the present series shows epidemiological agreement with the literature and may suggest that older patients trend to have hemoperitoneum more frequently, a fact that should be investigated in further studies.

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.

Hepatocellular Adenoma: Report of 2 Cases That Highlight the Relevance of Phenotype-Genotype Correlation in the Pediatric Population.

BACKGROUND: Hepatocellular adenoma (HCA) in the pediatric population is very rare and there are only limited studies, especially with molecular characterization of the tumors. Main HCA subtypes recognized in the current WHO classification include HNF1A-inactivated HCA (H-HCA), inflammatory HCA (IHCA), ß-catenin-activated HCA (b-HCA), and ß-catenin-activated IHCA (b-IHCA) and sonic hedgehog HCA (shHCA) is reported as an emerging subtype. METHODS: Clinical history, pathological information, and molecular studies for a series of 2 cases of pediatric HCA were reviewed. RESULTS: Case 1 was a b-HCA characterized by somatic CTNNB1 S45 mutation in a 11-year-old male with Abernethy malformation. Case 2 was a H-HCA characterized by germline HNF1A variant (c.526+1G>A) in a 15-year-old male associated with maturity-onset diabetes of the young type 3 (MODY3). CONCLUSION: Our findings highlight the rarity of these 2 cases associated with adenomatosis, and the contribution of molecular/genetic analysis for proper sub-typing, prognosis and family surveillance.

Hepatocellular adenoma subtyping by qualitative MRI features and machine learning algorithm of integrated qualitative and quantitative features: a proof-of-concept study.

AIM: To evaluate hepatocellular adenoma (HCA) subtyping using qualitative magnetic resonance imaging (MRI) features and feasibility of differentiating HCA subtypes using machine learning (ML) of qualitative and quantitative MRI features with histopathology as the reference standard. MATERIALS AND METHODS: This retrospective study included 39 histopathologically subtyped HCAs (13 hepatocyte nuclear factor (HNF)-1-alpha mutated [HHCA], 11 inflammatory [IHCA], one beta-catenin-mutated [BHCA], and 14 unclassified [UHCA]) in 36 patients. HCA subtyping by two blinded radiologists using the proposed schema of qualitative MRI features and using the random forest algorithm was compared against histopathology. For quantitative features, 1,409 radiomic features were extracted after segmentation and reduced to 10 principle components. Support vector machine and logistic regression was applied to assess HCA subtyping. RESULTS: Qualitative MRI features with proposed flow chart yielded diagnostic accuracies of 87%, 82%, and 74% for HHCA, IHCA, and UHCA respectively. The ML algorithm based on qualitative MRI features showed AUCs (area under the receiver operating characteristic curve [ROC] curve) of 0.846, 0.642, and 0.766 for diagnosing HHCA, IHCA, and UHCA, respectively. Quantitative radiomic features from portal venous and hepatic venous phase MRI demonstrated AUCs of 0.83 and 0.82, with a sensitivity of 72% and a specificity of 85% in predicting HHCA subtype. CONCLUSIONS: The proposed schema of integrated qualitative MRI features with ML algorithm provided high accuracy for HCA subtyping while quantitative radiomic features provide value for diagnosis of HHCA. The key qualitative MRI features for differentiating HCA subtypes were concordant between the radiologists and the ML algorithm. These approaches appear promising to better inform clinical management for patients with HCA.

Borderline Hepatocellular Adenomas: A Practical Diagnostic Approach Based on Pathologic and Molecular Features.

Borderline hepatocellular adenomas (BL-HCA) are characterized by focal architectural/cytologic atypia and reticulin loss, features that are insufficient for a definitive diagnosis of hepatocellular carcinoma (HCC). The diagnosis and management of BL-HCA are challenging as their biological behavior, especially in terms of malignant potential, is still debated. We aimed to compare the clinicopathologic and molecular features of BL-HCA with those of typical HCA (T-HCA), HCA with malignant transformation (HCC on HCA), and HCC to assess the risk of malignancy. One hundred six liver resection specimens were retrospectively selected from 2 reference centers, including 39 BL-HCA, 42 T-HCA, 12 HCC on HCA, and 13 HCC specimens. Somatic mutations, including TERT promoter mutations associated with HCA malignant transformation and the gene expression levels of 96 genes, were investigated in 93 frozen samples. Additionally, TERT promoter mutations were investigated in 44 formalin-fixed, paraffin-embedded samples. The clinical features of patients with BL-HCA were similar to those of patients with T-HCA, patients being mainly women (69%) with a median age of 37 years. The median tumor size was 7.5 cm, 64% of patients had a single nodule, and no recurrence was observed. Compared with T-HCA, BL-HCA was significantly enriched in ß-catenin-mutated HCA in exon 3 (41% vs 6%; P < .001). Unsupervised statistical analysis based on gene expression showed that BL-HCA overlapped with T-HCA and HCC on HCA, favoring a molecular continuum of the tumors. TERT promoter mutations were observed only in HCC on HCA (42%) and in HCC (38%). In conclusion, these results suggest that despite their worrisome morphologic features, the clinicopathologic and molecular features of BL-HCA are much closer to those of T-HCA than those of HCC on HCA or HCC. This strongly supports the usefulness of combining morphologic and molecular analyses in a practical diagnostic approach for guiding the management of BL-HCA.

Needle tract seeding and malignant transformation of hepatocellular adenoma into well-differentiated hepatocellular carcinoma in a dog.

An 11-year-old neutered female Golden Retriever was referred for investigation of marked increases in liver enzyme activities. Abdominal ultrasound revealed a large pedunculated liver mass. Diagnosis of hepatocellular adenoma (HCA) was made when the mass was excised after a first unsuccessful attempt through ultrasound-guided core-needle biopsy. One and a half years after presentation, a nodule embedded between muscles of the abdominal wall appeared. The mass was first diagnosed as a well-differentiated hepatocellular carcinoma (HCC) through cytologic examination, which was later confirmed with histopathology. Ki 67 immunostaining of the abdominal wall nodule showed an increased immunoreactivity compared with the liver mass. Therefore, the present case documents the first needle-tract seeding of a hepatocellular epithelial tumor with possible malignant transformation of HCA into a well-differentiated HCC in a dog.

Clinicopathologic characterization of hepatocellular adenomas in men: a multicenter experience.

Hepatocellular adenomas (HCAs) are benign liver neoplasms which most commonly present in women in their reproductive age. In men, they are rare and have a higher risk of malignant transformation to hepatocellular carcinoma (HCC). Here we present our multicenter experience with HCA in men in the United States. A total of 27 HCA cases were included, with a mean age of presentation of 37 years (range, 9-69 years) and a mean size of 6.8 cm (range, 0.9-18.5 cm). Based on the 2019 World Health Organization classification, the most common subtype identified was inflammatory HCA (IHCA; 10 cases, 37.0%) followed by unclassified HCA (UHCA; 7 cases, 25.9%), HNF1A-inactivated HCA (H-HCA; 6 cases, 22.2%), ß-catenin-activated IHCA (b-IHCA; 3 cases, 11.1%), and ß-catenin-activated HCA (b-HCA; 1 case, 3.7%). Six additional cases diagnosed as hepatocellular neoplasm of uncertain malignant potential (HUMP) were also included in the study. These cases presented in a mean age of 46 years (range, 17-64 years) and a size of 10.8 cm (range, 4.2-16.5 cm). We evaluated the significance of androgen receptor (AR) expression by immunohistochemistry (IHC); of the 16 cases with materials available, 8 were considered positive using the Allred score system (2 IHCA, 2 H-HCA, 1 UHCA, and 3 HUMP). Of the total cases, 12 were diagnosed on biopsies, for which follow-up information is available for 7, and none of them show evidence of malignant transformation. Of the 21 resection cases, a concomitant well-differentiated HCC within the same lesion was identified in 5 cases (23.8%), which were diagnosed as HCA (n = 4) or HUMP (n = 1). Overall, 15% of cases in our entire cohort of HCA and HUMP showed concomitant HCC, while none of the 7 biopsy cases showed any malignant transformation on follow-up (range, 22-160 months; mean, 61.8 months).