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.

Hepatic adenomatosis (HA) is a rare condition in which multiple adenomas exist in an otherwise healthy liver. The most common subtype (H-HA) is associated with bi-allelic, somatic hepatic nuclear factor 1-alpha (HNF1A) mutations. Maturity-onset diabetes of the young type 3 (MODY3) is most often seen in young individuals with heterozygous, germline mutations in HNF1A. In this report, we describe a 17-year-old woman with H-HA and non-familial MODY3.

Prader-Willi syndrome (PWS) is a genetic disorder caused by the lack of expression of genes on the paternally inherited chromosome region 15q11.2-q13. It is a multisystem disorder that is characterized by severe hypotonia with poor suck and feeding difficulties in early infancy, followed in early childhood by excessive eating and gradual development of morbid obesity. The incidence of type 2 diabetes mellitus is high, particularly in obese patients. Non-alcoholic fatty liver disease has also been reported in some patients with PWS. Liver adenomatosis is a benign vascular lesion of the liver, defined by the presence of >10 adenomas, in the otherwise healthy liver parenchyma. We report the first case of a patient with PWS with severe obesity, type 2 diabetes mellitus, and non-alcoholic fatty liver who also developed liver adenomatosis, review the pediatric literature on liver adenomatosis, and discuss the potential underlying mechanisms.

Hepatic adenomatosis (HA) is a very rare condition and defined as the presence of 10 or more adenomas in an otherwise normal liver. HA has an incidence of 10-24% in patient with hepatic adenoma and it is more common in women. Most patients with HA are asymptomatic with a normal liver function test and half of cases are detected incidentally on imaging. Although HA is considered a benign disease, some patients may develop potentially fatal complications, such as hypovolaemic shock due to rupture of the liver lesion or malignant transformation to hepatocellular carcinoma. We report the case of a 29-year-old woman who presented to the emergency room after a car accident. Whole-body computed tomography revealed multiple focal hepatic hypervascular lesions in the right lobe of the liver together with a fatty liver. Subsequent hepatic magnetic resonance imaging suggested the diagnosis of HA with a suspicion of focal nodular hyperplasia (FNH). The patient refused to undergo liver biopsy, so we instituted a 3-month surveillance program, which included clinical assessment, liver function tests, tumour marker assessment and blood tests as well as sonographic evaluation for follow-up of the liver lesions.
CONCLUSIONS: Hepatic adenomatosis is an extremely rare disease which predominantly affects women and is associated with hormone consumption, liver steatosis, glycogen storage disease, obesity, metabolic syndrome, abnormalities of hepatic vasculature and maturity onset diabetes of the young (MODY).The two main differential diagnoses include focal nodular hyperplasia (FNH) and well-differentiated hepatocellular carcinoma. Histological confirmation is required when MRI findings are inconclusive or when a malignancy is suspected.In men, resection of adenomas is mandatory due to the high risk of malignant transformation. In woman, a conservative approach with contraceptive discontinuation and biannual follow-up with MRI and alpha-fetoprotein is recommended; resection is needed in case of positive immunohistochemical staining for β-catenin on biopsy, symptomatic adenomas, adenoma increasing in size, and when malignancy cannot be ruled out.

OBJECTIVE: Known risk factors for hepatocellular adenoma (HCA) bleeding are size >5 cm, growth rate, visible vascularity, exophytic lesions, β-catenin and Sonic Hedgehog activated HCAs. Most studies are based on European cohorts. The objective of this study is to identify additional risk factors for HCA bleeding in a US cohort.
METHODS: Retrospective chart review was performed on patients diagnosed with HCA on magnetic resonance imaging (n = 184) at an academic tertiary institution. Clinical, pathological, and imaging data were collected. Primary outcomes measured were HCA bleeding and malignancy. Statistical analysis was performed with SAS 9.4 using Chi-Square, Fisher\'s exact test, sample t test, non-parametric Wilcoxon test, and logistic regression.
RESULTS: After excluding patients whose pathology showed focal nodular hyperplasia and non-adenoma lesions, follow-up data were available for 167 patients. 16% experienced microscopic or macroscopic bleeding and 1.2% had malignancy. HCA size predicted bleeding (P < .0001) and no patients with lesion size <1.8 cm bled. In unadjusted analysis, hepatic adenomatosis (≥10 lesions) trended towards 2.8-fold increased risk of bleeding. Of patients with a single lesion that bled, 77% bled from a lesion >5 cm. In patients with multiple HCAs that bled, 50% bled from lesions <5 cm. In patients with multiple adenomas, size (P = .001) independently predicted bleeding and hepatic steatosis trended towards increased risk of bleeding (P = .05).
CONCLUSIONS: In a large US cohort, size predicted increased risk of HCA bleeding while hepatic adenomatosis trended towards increased risk of bleeding. In patients with multiple HCAs, size predicted bleeding and hepatic steatosis trended toward increased risk of bleeding.

Hepatocellular adenoma (HCA) is an uncommon benign liver neoplasm usually solitary and identified incidentally on imaging. We report a case of a 50-year old female who was diagnosed with multiple hepatic adenomas of the inflammatory subtype. After discontinuation of oral contraception a decrease of both the number and size of the liver lesions was seen on magnetic resonance imaging (MRI) without the need of further intervention. The major challenge in the clinical management of patients with multiple HCAs resides in the risk assessment for future complications. In the case of multiple HCAs subtype seemed to be more relevant than the actual number of lesions. Because little is known about the natural evolution in patients with multiple HCAs, we performed a review of the current literature with focus on the different subtypes and their clinical relevance.

Hepatocellular adenoma (HCA) is a benign liver tumor most frequently occurring in women using oral contraception. HCA develops in normal or nearly normal livers and is extremely rare in cirrhosis. The authors present magnetic resonance imaging and histopathologic findings in a 57-year-old man with liver cirrhosis and hepatic adenomatosis. As the differentiation between HCA and hepatocellular carcinoma (HCC) can be difficult with imaging, we would like to highlight the importance of ancillary findings such as the presence of iron on MRI, which can be observed in HCA.

BACKGROUND: Hepatic adenomas are uncommon epithelial tumours. They usually appear in women between 20 and 44 years old. They are commonly located in the right hepatic lobe and are typically solitary masses. Multiple adenomas can present in patients with prolonged use of oral contraceptive pills, glycogen storage diseases and hepatic adenomatosis.
METHODS: A 35 year-old woman without any significant past medical history, with a chief complaint that started in December 2012 with oppressive, mild intensity abdominal pain located in right upper quadrant in the abdomen on deep palpation. With an abdominal ultrasound showing a mass of 91×82×65cm located in the right flank, isoechogenic with internal vascularity. Contrast computed tomography scan showing an ovoid tumour with circumscribed borders, with heterogenic intense reinforcement and displacement of adjacent structures with dimensions of 88×71×80cm. In laparotomy, excision of the tumour and cholecystectomy with the trans surgical findings of an 8cm tumour with a pedicle containing one artery and one vein coming from the hepatic free border with strong adhesions to the gallbladder. Pathologic diagnosis: Extracapsular hepatic adenoma.
CONCLUSIONS: Incidence of hepatic adenomas has increased in the last decades, in a parallel fashion with the introduction of oral contraceptive pills, showing association with glycogen storage diseases and to a lesser degree with diabetes and pregnancy. Diagnosis is clinical with the aid of imaging studies. Prognosis of hepatic adenomas is not well established, therefore, management depends on symptoms, size, number, location and certainty of diagnosis.

Hepatic adenomatosis and hepatocellular adenomas share risk factors and the same pathophysiologic spectrum. The presence in the liver of 10 hepatocellular adenomas defines hepatic adenomatosis. The diagnosis may be established incidentally during a liver radiologic examination in the asymptomatic patient, or after associated right upper quadrant pain, hepatomegaly or liver test abnormalities. Upon the diagnosis of hepatic adenomatosis or either of its life-threatening complications - hemorrhage and progression to hepatocellular carcinoma - consideration should be given to potential medical, radiologic and surgical interventions including: observation (estrogens and androgens withdrawal), resection, transarterial embolization, radiofrequency ablation and liver transplantation. The management of patients with hepatic adenomatosis can be challenging. These patients should be ideally referred to centers with expertise in the management of liver diseases.

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