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.
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.
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.

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

BACKGROUND: Focal nodular hyperplasia (FNH) and hepatocellular adenoma (HCA) are well-known benign liver lesions. Surgical treatment is usually chosen for symptomatic patients, lesions more than 5 cm, and uncertainty of diagnosis.
METHODS: We described the case of a large liver composite tumor in an asymptomatic 34-year-old female under oral contraceptive for 17-years. The imaging work-out described two components in this liver tumor; measuring 6 cm × 6 cm and 14 cm × 12 cm × 6 cm. The multidisciplinary team suggested surgery for this young woman with an unclear HCA diagnosis. She underwent a laparoscopic left liver lobectomy, with an uneventful postoperative course. Final pathological examination confirmed FNH associated with a large HCA. This manuscript aimed to make a literature review of the current management in this particular situation of large simultaneous benign liver tumors.
CONCLUSIONS: The simultaneous presence of benign composite liver tumors is rare. This case highlights the management in a multidisciplinary team setting.

This study evaluates 18F-FDG PET/CT imaging characteristics of pathologically proven hepatocellular adenoma (HCA) subtypes.
This is a retrospective review of an institutional database (2011-2017) for subjects with a pathologic diagnosis of hepatic adenomas established within 6 months of a pre-treatment 18F-FDG PET/CT exam. An expert pathological review by a hepatopathologist was performed to confirm diagnosis and subtype HCA. A review of the 18F-FDG PET/CT exams was performed by two board-certified nuclear radiologists in consensus. Corresponding demographic and clinical data were obtained by electronic chart review.
Nine subjects were identified. An HCA subtype was established in seven subjects (4 HNF1A-mutated and 3 Inflammatory). The mean HCA lesion size was 2.8 cm (range 0.6-6.2, SD 2.0) with a mean SUVmax of 5.9 (range 2.1-18.9, SD 5.1). The SUV values of HNF1A-mutated HCA were significantly higher than inflammatory HCA: lesion SUVmax (5.3 ± 1.48 vs. 2.8 ± 0.59, p < 0.033), lesion-to-liver SUVmax ratio (1.4 ± 0.22 vs. 0.8 ± 0.21, p = 0.031), lesion SUVmean (3.6 ± 0.37 vs. 2.0 ± 0.46, p = 0.0086).
HNF1A-mutated HCA may have greater SUV values than inflammatory HCA on 18F-FDG PET/CT exams. However, there are contradictory data in the literature and further investigation is warranted.

Hepatocellular adenoma (HCA) is a rare benign liver neoplasm which predominantly occurs in women in the reproductive age group taking oral contraception. Since 2002, the terminology HCA has defined an heterogeneous group of neoplastic benign hepatocellular proliferations composed of different subtypes. The genotype-phenotype classification led to the description of 5 well-recognized subtypes based on morphological and immunophenotypical features, that are currently used in practice: HNF1A inactivated HCA, inflammatory HCA, β-catenin mutated HCA, sonic hedgehog HCA, and unclassified HCA. The main complications observed in HCAs are bleeding and malignant transformation. Risk of malignant transformation into hepatocellular carcinoma (HCC), more frequent in men, is also dependent to tumor size and HCA subtype, reaching 40% in β-catenin mutated HCA. The distinction of HCA from well-differentiated HCC remains difficult in some cases, leading to the diagnosis of so-called \"atypical/borderline HCA\". The management of HCA is now based on multidisciplinary approach including clinicians, radiologists, and pathologists integrating gender, tumor size, and HCA subtyping.

Maturity-onset diabetes of the young type 3 (MODY 3) is a consequence of heterozygous germline mutations in HNF1A, and a subtype of hepatocellular adenoma (HCA) is caused by biallelic somatic HNF1A mutations; rare HCA may be related to MODY 3. This study aimed to investigate the cosegregation of HNF1A mutations with diabetes and HCA in two families.
Two patients suffering from HCA and diabetes were screened for HNF1A germline and somatic mutations using direct sequence analysis and methylation-specific multiplex-ligation-dependent probe amplification (MS-MLPA) assay. Further, we screened eight relatives in the two independent families for diabetes, HCA and HNF1A variants. Additionally, we reviewed the literature concerning the phenotypes of MODY 3 and HCA at the background of HNF1A mutations.
Here we reported two families (a total of six relatives) with two missense germline mutations of HNF1A identified initially using direct sequence analysis (c.686G>A in family A and c.526 + 1G>A in family B). Somatic deletion of the second allele of HNF1A was found in liver tumor tissues in both probands who were diagnosed with HCA. There are a total of ten cases of both MODY 3 and HCA phenotypes reported in the literature to date; incomplete penetrance for HCA was observed, and all the patients with HCA developed diabetes. The onset of diabetes and HCA was highly variable, the treatment of diabetes varied from diet to insulin, and the clinical expression of HCA ranged from silent to hemorrhage. Further, the severity of diabetes mellitus was not related to the occurrence of HCA.
This study describes the association of HCA and MODY 3 at the background of HNF1A mutations and highlights the importance of screening for HCA in MODY 3 families to avoid the possibility of severe complications. Further, the current study indicated that there may be a special mutational spectrum of HNF1A correlated with HCA in MODY 3 families.

UNASSIGNED: This review aims to highlight the clinicopathological characteristics and differential diagnosis of central hepatic regenerative nodules (CHRNs) in patients with Alagille syndrome.
UNASSIGNED: A review of the literature for cases of CHRNs and their differential diagnoses in patients with Alagille syndrome was performed and the main findings were collated.
UNASSIGNED: Large, regenerative hepatic nodules are seen in approximately 30% of patients with Alagille syndrome. They are thought to be a functional adaptation to vascular changes rather than a neoplastic process. The nodules are typically centrally located, and normal hepatic vasculature coursing through the lesions are noted radiologically. Microscopically, they are characterized by well-circumscribed hepatic lesions with preserved architecture, lesser degrees of fibrosis and relative preservation of interlobular bile ducts compared to the background cirrhotic liver.
UNASSIGNED: Regenerative nodules are common in Alagille\'s syndrome, and should be distinguished from hepatocellular carcinomas and adenomas for appropriate management and prognostication.

Histopathologists retain a critical role in the diagnosis and management of hepatocellular carcinoma (HCC). HCC arises usually but not exclusively in a background of advanced-stage chronic liver disease. The histological diagnosis of HCC poses many challenges particularly when dealing with liver biopsy specimens due to the heterogeneity of HCC and the difficulty to confirm hepatocellular differentiation in some instances. Primary liver tumors should be considered as a continuum with typical hepatocellular and cholangiocarcinoma at the two ends and a whole range of tumors showing both hepatocellular and cholangiocellular differentiation with or without an associated progenitor/stem cell component in the middle. Characterization of combined (or mixed) hepatocellular-cholangiocarcinoma can be very challenging. In advanced-stage chronic liver disease, the main challenge for the histopathologist is still to differentiate between HCC and its precursors, although this is rarely critical in the clinical setting at present. HCC originating in non-cirrhotic livers needs to be differentiated from other primary and extrahepatic tumors and from hepatocellular adenoma, bearing in mind that progression to malignancy is more through a continuum that watertight histological categories.

A 47-year-old woman was referred to our department for a hepatic mass. She denied history of hepatitis or alcohol consumption and regular oral contraceptive use, except for the emergency contraceptive pill taken once a decade ago. Hepatitis B surface antigen and anti-hepatitis C antibody were negative, α-fetoprotein was within normal limit. CT scan revealed an enormous mass measuring 26.0×16 5×13 0 cm that almost totally replaced the right hepatic lobe. The neoplasm was completely resected and pathologically diagnosed as hepatic adenoma. Literature review indicates this is the largest hepatic adenoma reported so far. At the same time, clinical examination also revealed a hepatic mass in the patient\'s 42-year-old brother, which was pathologically confirmed as hepatic adenoma, too. He denied history of anabolic steroid use. Immunohistochemical analysis revealed the subtypes of both tumors as the inflammatory hepatic adenoma. Literature review indicates this is the first report of synchronous hepatic adenomas in siblings.

Synthetic astaxanthin has been extensively tested for safety. Genotoxicity studies including Ames and in vitro Micronucleus Tests show absence of genotoxic potential. Although a long-term mouse study showed no carcinogenicity potential, the rat carcinogenicity study with dietary dosages of 0 (control), 0 (placebo beadlet), 40, 200 and 1000 mg astaxanthin/kg bw/day showed an increased incidence of benign, hepatocellular adenoma in females only, at 200 mg/kg bw/day and above. There was no clear evidence of toxicity during the in-life phase. Discoloration of feces was observed and a reduction in body weight gain in all groups receiving beadlets, probably reflecting a nutritional influence. Blood sampling confirmed systemic exposure and some minor clinical chemistry differences in females at 200 and 1000 mg/kg bw/day. There was no effect on adjusted liver weight. Histopathological examination showed hepatic changes indicative of slight hepatotoxicity and hepatocyte regeneration in females at 200 and 1000 mg/kg bw/day, in addition to the adenoma. Taking into account this pathological background in the female rat, and a wide variety of other supporting information, it is concluded that the hepatocellular adenoma in female rats was secondary to hepatotoxicity and regeneration, and is most probably a species-specific phenomenon of doubtful human relevance.