Multiple Focal Nodular Hyperplasia Research Articles

Hepatobiliary and Pancreatic: Hepatic mass discovered incidentally with telangiectasia.

A 48-year-old woman with no history of alcohol use or medical history was referred to our hospital for abnormal endoscopic and liver sonography findings collected at another hospital. An gastric angiodysplasia (telangiectasia) on endoscopy and two suspicious liver echogenic masses in hepatic S4 and S6 were detected. Her laboratory tests, including liver function tests and tumor markers, were within the normal ranges and the viral markers were negative. Autoimmune antibodies related to autoimmune hepatitis were negative. As she had a severe allergic reaction to the computed tomography (CT) contrast agent, she underwent liver magnetic resonance imaging (MRI) for further evaluation. The liver MRI revealed dozens of hypervascular nodules of various sizes with a central scar and diffuse vascular abnormalities with peripheral vascular obliteration (Fig. 1a). She had experienced intermittent bleeding of the tongue and several telangiectasias were observed on her tongue (Fig. 1b). The differential diagnoses included hepatocellular adenoma and multiple focal nodular hyperplasia (FNH) syndrome with primary or secondary hepatic vascular abnormalities. Osler-Weber-Rendu disease (hereditary hemorrhagic telangiectasia [HHT]) was also possible considering the diffuse vascular abnormalities in the liver and the telangiectasia on the tongue. The pathology report based on the targeted liver biopsy described a hepatocellular nodular lesion composed of bland looking hepatocytes with sinusoidal dilatation and abnormal vessels, suggesting FNH or hepatocellular adenoma; however, immunohistochemical staining did not confirm either disease (Fig. 2). On the annual MRI follow up, innumerable hypervascular nodules, irregular heterogeneous enhancement of the liver (Fig. 3a), and diffuse vascular abnormalities with peripheral vascular obliteration (Fig. 3b) were the major findings, with no changes seen from the previous exam. Given that the pathology report did not definitively diagnose hepatocellular adenoma or multiple FNH syndrome, a hepatic vascular disorder such as HHT was considered in the differential diagnosis and genetic testing was performed. HHT is an autosomal dominant inherited disorder that affects the vasculature and is considered a rare disease, with a prevalence of 1 in 5000 or 1 in 10 000 births. The pathogenesis of HHT is a heterozygous mutation in the endoglin (ENG) gene or the activin receptor-like kinase type 1 gene, both of which are associated with the transforming growth factor-β superfamily signaling pathway, expressed mostly in the vascular endothelium. As 97% of patients with definite HHT carry a mutation in one of three genes, including ENG, a mutation in a locus mapped to chromosome 5, or an activin receptor-like kinase-1 (ACVRL1), we consulted the genetics department to evaluate the patient for HHT. HHT has traditionally been diagnosed based on clinical features (the Curacao criteria), but can now also be diagnosed by genetic testing. HHT is clinically suspected if two of the four Curacao criteria are met (family history of the disease, hemorrhage, telangiectasia, and visceral involvement) and definite if more than three of the criteria are met. The presence of intrahepatic shunts, disseminated intraparenchymal telangiectases, and other vascular lesions are the typical findings of hepatic involvement. In this patient, three (epistaxis, telangiectasia, and visceral involvement) of the four Curacao criteria were satisfied, leading to a definite diagnosis of HHT. Next-generation sequencing (NGS) panel performed also showed heterozygous mutation of the ACVRL1 (ALK1) gene, which is consistent with HHT type 2.

Hepatocyte-specific contrast-enhanced MRI findings of focal nodular hyperplasia-like nodules in the liver following chemotherapy in pediatric cancer patients

We aimed to assess the MRI findings and follow-up of multiple focal nodular hyperplasia (FNH)- like lesions in pediatric cancer patients diagnosed by imaging findings. We retrospectively analyzed clinical data and MRI examinations of 16 pediatric patients, who had been scanned using gadoxetate disodium (n=13) and gadobenate dimeglumine (n=3). Hepatic nodules were reviewed according to their number, size, contour, T1- and T2-weighted signal intensities, arterial, portal, delayed and hepatobiliary phase enhancement patterns. Follow-up images were evaluated for nodule size, number, and appearance. All 16 patients received chemotherapy in due course. Time interval between the initial diagnosis of cancer and detection of the hepatic nodule was 2-14 years. Three patients had a single lesion, 13 patients had multiple nodules. The median size of the largest nodules was 19.5 mm (range, 8-41 mm). Among 16 patients that received hepatocyte-specific agents, FNH-like nodules appeared hyperintense in 11 and isointense in 5 on the hepatobiliary phase. During follow-up, increased number and size of the nodules were seen in 4 patients. The nodules showed growth between 6-15 mm. Liver MRI using hepatocyte-specific agents is a significant imaging method for the diagnosis of FNH-like lesions, which can occur in a variety of diseases. Lesions can increase in size and number in pediatric patients.

Multiple focal nodular hyperplasia: MRI features

PurposeTo describe MRI features of multiple Focal Nodular Hyperplasia (FNHs). Methods40 consecutive subjects (37 females, mean age, 38.8years) were included. All studies were independently reviewed. This was an observational study to define the radiological features of multifocal FNH. Results130 lesions were evaluated. The majority (88.5%), were peripheral in location. 92.3% lesions were lobulated. Marked enhancement was present in 94.6% lesions. In the portal venous and delayed phase, 46.2% and 47.7% lesions were mildly hyperintense. Central scar was present in 77% lesions. ConclusionsDistinctive features included predominant subcapsular location and mild hyperintensity in the delayed phase, seen in nearly 50% of FNHs.

Multiple focal nodular hyperplasias induced by oxaliplatin-based chemotherapy

Focal nodular hyperplasia (FNH) is a benign condition that affects normal liver with low prevalence. Recently, the extensive use of oxaliplatin to treat patients with colorectal cancer has been reported to be associated with the development of different liver injuries, as well as focal liver lesions. The present work describes two patients with multiple bilateral focal liver lesions misdiagnosed as colorectal liver metastases, and treated with liver resection. The first patient had up to 15 small bilateral focal liver lesions, with magnetic resonance imaging consistent with colorectal liver metastases (CLM), and fluorodeoxyglucose (FDG)-positron emission tomography (PET) negative. The second patient had up to 5 small focal liver lesions, with computed tomography consistent with CLM, and FDG-PET negative. They had parenchyma sparing liver surgery, with uneventful postoperative course. At the histology the diagnosis was multiple FNHs. The risks of oxaliplatin-based chemotherapy regimens in development of liver injuries, such as FNH, should not be further denied. The value of the modern multidisciplinary management of patients with colorectal cancer relies also on the precise estimation of the risk/benefit for each patient.

Multiple Hypervascular FNH-like Lesions in a Patient with No History of Alcohol Abuse or Chronic Liver Disease

A 64-year-old Japanese woman with a history of bronchiectasis presented with multiple hypervascular nodules in both lobes of the liver without hepatitis B or C virus infection. Imaging studies, including ultrasound, contrast-enhanced computed tomography and magnetic resonance imaging, showed hypervascularity in the early phase. Histologically, no lipid degeneration was observed; however, there was a mild increase in cell density, miniaturization of nuclei, increased chromatin content, partial sinusoidal dilatation and congestion. No unpaired arteries were evident. The diagnosis based on the pathology and diagnostic radiology findings was multiple hypervascular focal nodular hyperplasia (FNH)-like lesions with no history of alcohol abuse or chronic liver disease.

Liver involvement in Turner syndrome

Liver test abnormalities are frequent in adult patients with Turner syndrome, corresponding to various pathophysiological mechanisms. Steatosis, steatofibrosis and steatohepatitis are the most frequently reported lesions, caused by metabolic disorders, which are commonly related to overweight. Marked architectural changes, including nodular regenerative hyperplasia, multiple focal nodular hyperplasia and cirrhosis, found in some patients, are associated with a risk of severe liver-related complications. Architectural changes are often observed and are associated with vascular disorders caused by congenitally abnormal vessels. Finally, small bile duct alterations resembling sclerosing cholangitis occur in several patients. Oestrogen replacement therapy does not cause liver toxicity in patients with Turner syndrome and is not contraindicated in case of elevated liver enzymes. Moreover, in recent studies, oestrogen therapy was reported to improve liver function tests. Because of the wide spectrum of potential liver injuries that may occur in Turner syndrome patients, a regular screening of liver enzymes is recommended for early detection and treatment.

Synchronous occurrence of multiple focal nodular hyperplasia and huge hepatic perivascular epithelioid cells tumor (PEComa) in young woman after oral contraceptive use--is there a common pathogenesis?

The association of focal nodular hyperplasia (FNH) and various neoplasms was described, but coincidence of multiple FNH and hepatic perivascular epithelioid cells tumor (PEComa) has not been reported. The clinical debate of oral contraceptive (OC) influence on FNH growth is ongoing, but no evidence exists about association of hepatic PEComa with OC use. Herein, we report a case of two FNH lesions and huge (150x100x80 mm) left hepatic lobe PEComa that occurred simultaneously in 18-year-old female with previous two year history of OC use, who underwent left hemihepatectomy and right hepatic FNH enucleation. Up to date, the patient has been followed-up for 65 months and remained disease-free. FNH and PEComa have a common vascular cytogenetic denominator. Our case raising a question of a causal relationship of FNH and PEComa with OC use that might be attributed to vascular changes. Future researches of larger sample sizes should further address this issue.

Hepatic adenomatosis: spectrum of imaging findings

This pictorial essay reviews the imaging appearance and differential diagnosis of hepatic adenomatosis. In addition to such entities as multifocal hepatocellular carcinoma, metastases, and multiple focal nodular hyperplasia, hepatic adenomatosis should also be considered when confronted with multiple hypervascular liver lesions. Certain CT and MRI features can strongly suggest the diagnosis of adenomatosis.

Multiple focal nodular hyperplasia, an incidental finding on autopsy.

Focal nodular hyperplasia (FNH) is a benign condition of the liver often discovered incidentally on radiological investigation. Although FNH is a well-described lesion in the literature considerable diagnostic problems regarding this entity still remains. We report a case of multiple FNH in a 23-year-old male patient detected as an incidental finding in autopsy. On gross examination FNH was not suspected because of the multiple lesions and the lack of central scar which is characteristically described in FNH. The diagnosis was established on histopathology after examination of multiple sections of the lesions.

Multiple focal nodular hyperplasia lesions of the liver associated with congenital absence of the portal vein

Congenital absence of the portal vein (CAPV) is a rare anomaly in which the intestinal and splenic venous drainage bypass the liver and drain directly into the systemic veins through various porto-systemic shunts. In this article, we illustrate a case of multiple focal nodular hyperplasia (FNH) with congenital absence of the portal vein in a male, which, to our knowledge, is the third reported case in the literature since its first description in 1793. Furthermore, we discuss the embryology of the portal vein and the Morgan and Superina classification of portosystemic anomalies, the association between portal vein agenesis and multiple FNHs, and, lastly, the use of a hepatocellular-specific MRI contrast agent as an important diagnostic tool in the confirmation of FNH.

A Case of Multiple Focal Nodular Hyperplasia in the Liver Which Developed after Heart Transplantation

An 18-year-old woman, who had undergone cardiac allograft transplantation, developed continuous back pain two months after surgery. Abdominal computed tomography showed multiple enhanced lesions in her liver, which were not present before transplantation. One tumor bulged from the surface of the liver and compressed the stomach. Partial resection of the liver was performed and her symptoms improved. The pathological diagnosis was focal nodular hyperplasia (FNH). To our knowledge, this is the first report of multiple FNH after heart transplantation. Transplant clinicians may need to keep this possibility under consideration following heart transplantation.

MRI findings of multiple focal nodular hyperplasia of the liver

Objective To assess the diagnostic value of MRI on multiple focal nodular hyperplasia (FNH) of the liver. Methods MR images of 9 cases with pathological-confirmed multiple FNH were retrospectively analyzed. MRI features of the lesions were correlated with pathological findings. Results Multiple FNH was considered in all these 9 cases. Among them, the primary diagnosis was FNH in 5,hepatic adenoma in 3 and fibrolamellar hepatocellular carcinoma in 1 case. A total of 31 lesions were detected in the 9 cases. On T2WI, 19 lesions presented slightly high-signal intensity, and the other 12 presented iso-signal intensity. On T1WI, 12 lesions presented slightly low-signal intensity, 7 presented iso-signal intensity, and the other 12 presented high-signal intensity. On opposed-phase, the signal intensity of 1 lesion dropped unevenly. After bolus injection of contrast agent Gd-DTPA, in hepatic arterial phase 18 lesions showed mild to marked heterogeneous enhancement, 11 showed marked homogeneous enhancement, 1 showed moderate ring-like enhancement, and the last one did not have obvious enhancement In portal venous and delayed phase, all the lesions turned to iso- or slightly high-signal intensity gradually. Sixteen of 31 lesions presented central scar, which demonstrated mild star-like enhancement in delayed phase. Conclusion Multiple FNH presented certain MRI features, which contributed to the preoperative diagnosis. Key words: Liver neoplasm; Magnetic resonance imaging

USEFULNESS OF POWER DOPPLER ULTRASONOGRAPHY AND SUPERPARAMAGNETIC IRON OXIDE ENHANCED MAGNETIC RESONANCE IMAGING FOR DIAGNOSIS OF FOCAL NODULAR HYPERPLASIA OF THE LIVER AFTER TREATMENT OF NEUROBLASTOMA

Focal nodular hyperplasia (FNH) of the liver is rare in children, and it is usually diagnosed through a biopsy of the liver or hepatectomy. The authors report a case of a 10-year-old girl with multiple focal nodular hyperplasia lesions of the liver after the completion of tumor therapy for advanced neuroblastoma, and review the usefulness of the combination of power Doppler ultrasonography (US) and superparamagnetic iron oxide (SPIO) enhanced magnetic resonance imaging (MRI) for the diagnosis of FNH without a biopsy of the liver or hepatectomy.

Multiple progressive focal nodular hyperplasia lesions of liver in a patient with hemosiderosis

Focal nodular hyperplasia (FNH) is the second most common benign lesion of the liver. It is a solitary lesion and usually does not enlarge. We present the magnetic resonance imaging findings of multiple progressive FNH lesions in a patient with hemosiderosis using Gadolinium-EOB-DTPA (Eovist) as a hepatobiliary contrast agent. The possible mechanisms underlying the occurrence and progression of FNH lesions and the potential value of Eovist in characterizing the lesions were discussed.

Multiple focal nodular hyperplasia of the liver associated with spinal and pulmonary arteriovenous malformations

Focal nodular hyperplasia (FNH) is frequently found incidentally in liver imaging but multiple FNH, especially when associated with systemic vascular malformations, are rare. We report on the case of a patient with lumbar sciatalgia and paraparesis. Spinal magnetic resonance angiography (MRA) showed a spinal cord arteriovenous shunt (SCAVS), its arterial feeders and venous drainage, which were later confirmed by digital subtraction angiography (DSA). MRA of the spine offers promising results in the characterization of SCAVS. Thoracoabdominal CT and MRI revealed multiple hepatic FNH and a pulmonary arteriovenous malformation (AVM). Indeed, this is the first reported case of the rare multiple FNH syndrome associated with a spinal AVM.

Radiological Findings in a Case of Multiple Focal Nodular Hyperplasia Associated with Portal Vein Atresia and Portopulmonary Hypertension

We present here the radiological findings of a rare case of multiple focal nodular hyperplasia that was associated with portal vein atresia and portopulmonary hypertension in a young woman. This case illustrates and supports the pathophysiological hypotheses that were previously proposed for the coexistence of these three abnormalities.

Hepatic disease in Turner syndrome

Liver test abnormalities are frequent in adult patients with Turner syndrome, but only few histological studies have been reported in the literature. The hepatic histological changes found in TS patients may be explained by one or more distinct physiopathological mechanisms. Marked architectural changes, including nodular regenerative hyperplasia, multiple focal nodular hyperplasia and cirrhosis, are observed in some patients and are associated with a risk of severe liver-related complications. These changes are frequently associated with vascular disorders that are probably related to congenitally abnormal vessels. Steatosis, steatofibrosis and steatohepatitis are frequent, caused by metabolic disorders. Finally, bile duct alterations resembling small duct sclerosing cholangitis are observed in several patients. There is no evidence for liver toxicity due to oestrogen replacement therapy.

Multiple Focal Nodular Hyperplasia: Atypical Imaging Characteristics in the Setting of Hepatic Steatosis

Focal nodular hyperplasia is an uncommon, benign lesion of the liver most often affecting women of childbearing age. It can present clinically with chronic, intermittent right upper quadrant pain and nausea, with associated liver enzyme abnormalities. The presence of characteristic sonographic and computed tomography imaging findings can help to differentiate this entity from other hepatic masses. This article describes an unusual case of multifocal disease that demonstrates atypical imaging findings in the background of hepatic steatosis.

Focal nodular hyperplasia in oncology patients

Sir, A case of multiple focal nodular hyperplasia (FNH) in a patient treated for stage III neuroblastoma was presented at the Midwest Society for Pediatric Radiology Meeting in September 2005 at Madison, Wisconsin. The patient received carboplatin, cyclophosphamide, Adriamycin, vincristine, cisplatin, and etoposide chemotherapy, right paraspinal thoracic irradiation, and stem cell bone marrow transplantation. Two years after initiation of retinoic acid therapy and 3 years after the diagnosis of neuroblastoma, numerous hepatic lesions (hyperdense on portal venous phase and isodense on delayed phase) were noted on surveillance CT imaging. Several new lesions were found on a short-term follow-up CT examination. This case complements the article by Joyner et al. [1] in Pediatric Radiology and allows some additional points: (1) other drugs may be implicated in the development of FNH, (2) chemotherapy-induced FNH may not necessarily be a late complication, and (3) knowledge of this complication may not necessarily obviate the need for biopsy. While many of the drugs used to treat this patient are associated with the development of FNH, retinoic acid should also be considered. The chemotherapeutic effect of retinoic acid is related to its promotion of cytodifferentiation and apoptosis. However, retinoic acid also has prothrombotic effects by inducing endothelial coupling of coagulation factors. Retinoic acid has been implicated in various thrombotic events including myocardial infarction, pulmonary embolism, venous thrombosis and stroke [2]. The time to development of FNH noted by Bouyn et al. [3] is 8.5 years for cytoreductive chemotherapy and 12.3 years for other chemotherapy. One of three cases presented by Joyner et al. occurred 3 years after diagnosis. The case presented here also occurred 3 years after diagnosis. While development of FNH is typically late, lesions can occur early and could be confused with metastatic disease. FNH can have many imaging appearances, and there is overlap with hepatic adenoma, hypervascular metastasis, and other hepatic malignancies [4]. While the diagnosis of FNH was suggested in the current patient, the lack of a central scar and the number of lesions resulted in a shortterm follow-up examination. The increase in the number of lesions on the follow-up examination was unsettling and resulted in confirmation of the diagnosis with biopsy. In conclusion, retinoic acid may be another drug implicated in development of FNH, chemotherapy-induced FNH may occur early, and biopsy may be necessary to confirm the diagnosis in atypical cases.

Liver-Occupying Focal Nodular Hyperplasia and Adenomatosis Associated with Intrahepatic Portal Vein Agenesis Requiring Orthotopic Liver Transplantation

An 11-year-old Hispanic girl presented to our hospital with persistent abdominal pain. She was known to have a focal nodular hyperplasia (FNH) since 3 years of age, and underwent surgical resection at 4 years old due to severe abdominal pain. She remained asymptomatic until recently, but recurrence was noted at the age of 7 years. Over the past several weeks, she has been experiencing moderate to severe episodes of right upper quadrant pain which was only partially ameliorated by analgesics. The laboratory tests showed elevated alkaline phosphatase 737 U/L, ALT 125 U/L and ALT 70 U/L, but were otherwise normal including alpha-feto-protein. Metabolic disorders and autoimmune liver disease were ruled out, and serologies including hepatitis A, B, and C viruses and cytomegalovirus were negative. An abdominal computed tomography (CT) scan revealed numerous lesions, up to 6.5 cm in diameter, filling the liver (Fig. 1A). Three-dimension CT showed blood flow from the confluence of the superior mesenteric vein (SMV) and splenic vein (SV) directly draining into the inferior vena cava (IVC), and no portal venous flow into the liver (Fig. 1B).FIGURE 1.: (A, B) Computed tomography (CT) scan of the abdomen. (A) An axial tomography scan showed multiple varying-sized lesions filling the liver, with the size of up to 6.5 cm in diameter. (B) Three-dimensional restructuring image of CT revealed a blood flow shunt of the superior mesenteric vein and splenic vein draining into the inferior vena cava directly outside the liver without any flow of portal vein into the liver. A, abdominal aorta; I, inferior vena cava; P, portal vein; Sp, splenic vein; S, superior mesenteric vein. (C) Macroscopic examination of the specimen. Multiple varying-sized well-circumscribed tan-golden nodules, which had thin, fibrous septae traversing throughout, were occupying the liver. (D) Histological examination of the specimen (H&E stain, ×40). All the nodules exhibited scarring, and there were also abundant solitary arteries within the surrounding nodular tissues.Although other options including ablation therapy were considered, surgical intervention was chosen due to progressive, recurrent, and liver-occupying characteristics of the tumors. She was approved for liver transplantation and underwent orthotopic liver transplantation. During the operation, the direct portocaval connection underneath the pancreas, and the absence of portal vein (PV) into the liver were confirmed. Liver transplantation was done in a piggyback fashion, and portoportal flow was established after the recipient PV detached from the IVC. Pathologic examination of the specimen showed multiple varying-sized well-circumscribed tan-golden nodules ranging from 1.3 to 5.8 cm, having a rubbery consistency with thin, fibrous septae traversing throughout (Fig. 1C). All the nodules exhibited scarring, but there were also abundant solitary arteries within the surrounding nodular tissues (Fig. 1D). There were no atypical cells in the nodules, nor cirrhosis in the background liver tissue. The diagnosis of both multiple FNH and adenomatosis was made. She recovered well and was discharged on postoperative day 10. Intrahepatic portal vein agenesis (IPVA), or congenital absence of portal vein, represents a portosystemic shunt in which there is no portal perfusion of the liver (1, 2). Embryologically, the portal vein derives from selective involution and persistence of the vitelline venous system. Abnormal involution and persistence may result in an absence of a PV (1). IPVA is a rare congenital anomaly and only 28 cases have been reported in the literature to our knowledge (1–4). Benign hepatic neoplasms including focal nodular hyperplasia (FNH) and adenoma are frequently associated with IPVA (5). Abnormalities of hepatic circulation have been suggested as possible etiological factors in benign nodular hepatocellular lesions (5). Both the arterial and portal blood flows may be impaired by anomaly or variation of the portal tract, and this blood flow disturbance is thought to cause hyperplasia and consequent nodule formation in areas with a richer blood flow (5). Hepatic resection was required in some reported cases due to progressive growth of those hepatic nodules (3, 4). One patient with IPVA and hepatoblastoma was treated by liver transplantation. The current report is the first case of IPVA associated with progressive benign hepatic nodules successfully treated by liver transplantation. Although hepatic nodules including FNHs and adenomas are histologically benign, the persistent severe abdominal pain associated with these liver-occupying lesions, as well as their progressive growth characteristics, lead us to surgical intervention. Our case extends the indications for liver transplantation to treatment of IPVA with progressive hepatic nodules. Shiro Fujita Kristin L. Mekeel Takahisa Fujikawa Robin D. Kim David P. Foley Alan W. Hemming Richard J. Howard Alan I. Reed Division of Transplantation and Hepatobiliary Surgery, Department of Surgery, University of Florida College of Medicine, Gainesville, FL Lisa R. Dixon Department of Pathology, University of Florida College of Medicine, Gainesville, FL