Focal nodular hyperplasia of the liver in 86 patients

BACKGROUND: Focal nodular hyperplasia (FNH), the second most common benign hepatic tumor after hemangioma, is characterized by a stellate central scar and hyperplastic nodules. Although some large FNH may be associated with significant symptoms, more frequently they are discovered incidentally on physical examination or the work-up of unrelated symptoms. Since its nature and pathogenesis are still controversial, accurate diagnosis of FNH based on clinical presentation and radiographic studies is difficult. The purpose of this study was to explore the diagnosis and treatment of FNH. METHODS: Eighty-six FNH patients confirmed pathologically were treated at the Liver Cancer Institute in our hospital from 1996 to 2006. Their clinical manifestions, imaging presentation, pathological findings, and surgical results were analyzed retrospectively. RESULTS: Of the 86 patients with 99 foci, 54 were male and 32 female, with a mean age of 37 years. Eighty patients had a single solitary focus and 6 had multiple foci. Tumor diameter was less than 5 cm in 69 patients, 5-10 cm in 15, and more than 10 cm in 2. The overall rate of correct preoperative diagnosis was 59.3% (51/86) including 32.9% (26/79) by color Doppler flow imaging (CDFI), 60.3% (35/58) by CT, and 77.4% (24/31) by MRI. All the 86 patients underwent resection with good curative effect. CONCLUSIONS: CT and MRI are important diagnostic methods for FNH but it is difficult to make a definite preoperative diagnosis for partial classical and all non-classical FNH patients. We suggest that patients with clinical symptoms or with indefinite diagnosis should accept surgical removal.

Complete spontaneous regression of giant focal nodular hyperplasia of the liver: Magnetic resonance imaging evaluation with hepatobiliary contrast media

Focal nodular hyperplasia(FNH) of the liver is a benign lesion occurring in 0.6%-3% of the general population that probably reflects a local hyperplastic response of hepatocytes to a vascular abnormality. Most lesions are diagnosed incidentally and the natural history of the disease remains largely unknown. It has been shown that most FNH remain stable, or even regress, over a long follow-up period. We present a patient with FNH of the liver who was followed up for 7 years. A 26-yearold woman with a 5-year history of oral contraceptive use was referred to our hospital in February 2005 for further examination of a liver tumour. The diagnosis of FNH was made using magnetic resonance(MR) imaging with hepatospecific contrast media; this technique allows a correct diagnosis, in particular distinguishing FNH from hepatic adenoma, avoiding an invasive procedure such as the lesion biopsy. After 7-year from the diagnosis, we observed the complete spontaneous regression of the lesion by enhanced MR scanning. In this patient, discontinuation of oral contraceptive use and two childbirths may have influenced the natural history of FNH. To our knowledge, in the English literature there is no report illustrating a complete regression of giant FNH but only studies of decreasing in size. The present case suggests that a young patient with giant FNH should be managed conservatively rather than by resection, because FNH has the potential for spontaneous regression.

Hepatocellular carcinoma and focal nodular hyperplasia of the liver in a glycogen storage disease patient

Glycogen storage disease type Ia (GSD-Ia; also called von Gierke disease) is an autosomal recessive disorder of carbohydrate metabolism caused by glucose-6-phosphatase deficiency. There have been many reports describing hepatic tumors in GSD patients; however, most of these reports were of hepatocellular adenomas, whereas there are only few reports describing focal nodular hyperplasia (FNH) or hepatocellular carcinoma (HCC). We report a case with GSD-Ia who had undergone a partial resection of the liver for FNH at 18 years of age and in whom moderately differentiated HCC had developed. Preoperative imaging studies, including ultrasonography, dynamic computer tomography (CT) and magnetic resonance imaging, revealed benign and malignant features. In particular, fluorodeoxyglucose-positron emission tomography (FDG-PET)/CT revealed the atypical findings that FDG accumulated at high levels in the non-tumorous hepatic parenchyma and low levels in the tumor. Right hemihepatectomy was performed. During the perioperative period, high-dose glucose and sodium bicarbonate were administered to control metabolic acidosis. He had multiple recurrences of HCC at 10 mo after surgery and was followed-up with transcatheter arterial chemoembolization. The tumor was already highly advanced when it was found by chance; therefore, a careful follow-up should be mandatory for GSD-I patients as they are at a high risk for HCC, similar to hepatitis patients.

Focal nodular hyperplasia of the liver: pathological analysis of 11 cases

BACKGROUND: Focal nodular hyperplasia (FNH) is a benign tumor-like lesion of the liver, predominantly affect- ing women. Its etiology is obscure and its pathogenesis is poorly understood. FNH should be differentiated from oth- er benign and malignant hepatic lesions. The aim of this study was to explore the pathological characteristics of FNH of the liver. METHODS: Eleven patients with FNH were studied retro- spectively by using hematoxylin and eosin, immunohisto- chemical and histochemical staining. RESULTS: In 8 female and 3 male FNH patients aged 19 to 54 years (mean 32), most of lesions showed central scars macroscopically. Microscopically 8 patients were found of classical type, 2 were of telangiectic type, and 1 was of mixed type. CONCLUSION: FNH is an uncommon benign hyperplastic lesion of the liver. It should be differentiated from hepato- cellular adenoma, alpha-fetoprotein negative hepatocellular carcinoma, and fibrolamellar carcinoma.

Atypical focal nodular hyperplasia of the liver

BACKGROUND:Focal nodular hyperplasia,a benign hepatic tumor,is usually asymptomatic.However,rarely the entity can cause symptoms,mandating intervention. METHOD:We present a case of focal nodular hyperplasia of the liver,which caused a considerable diagnostic dilemma due to its atypical presentation. RESULTS:A 29-year-old woman presented with a 15-year history of a progressively increasing mass in the right upper quadrant which was associated with pain and emesis. Examination showed a firm,mobile mass palpable below the right subcostal margin.A computed tomography scan of the abdomen showed an exophytic mass arising from hepatic segments III and IVb.Trucut biopsy of the hepatic mass was equivocal.Angiography showed a vascular tumor that was supplied by a tortuous branch of the proper hepatic artery. Surgical intervention for removal of the mass was undertaken. Intra-operatively,two large discrete tumors were found and completely resected.Histopathological examination showed features consistent with focal nodular hyperplasia. CONCLUSION:This description of an unusual case of focal nodular hyperplasia of the liver highlights the point that the diagnosis of otherwise benign hepatic tumors may be difficult despite extensive work-up in some cases.

Transarterial Embolization Using Pingyangmycin-Lipiodol Emulsion (PLE) for Treatment of Focal Nodular Hyperplasia of the Liver and 1-Year Follow-Up: A Case Report and Literature Review

Focal nodular hyperplasia (FNH) is a common benign hepatic tumor which is often treated non-operatively until it appears apparent symptoms such as pain and upper abdominal distension. We report here a case of trans-catheter arterial embolization (TAE) using pingyangmycin-lipiodol emulsion (PLE) for blocking a fatal bleeding originated from percutaneous biopsy as well as for FNH treatment. After embolization by means of the mixture of PLE and particles of gelfoam, the bleeding was stopped and the FNH was apparently shrinked 1 year later. TAE using PLE may be considered as a safe and effective method for the treatment of FNH.

Plane and weighted tri-phase helical CT findings in the diagnosis of liver focal nodular hyperplasia

Objective: To analyze the pre- and post-contrast CT findings of liver focal nodular hyperplasia (FNH) so as to improve their diagnostic accuracy. Methods: Pre- and post-contrast tri-phase (arterial, portal venous and delayed) scans were performed in 21 patients with FNH proved surgically and patholo- gically. Transcatheter arterial angiography was per- formed in 2 patients. Results: Pre-contrast scans showed hypodensity in 16 patients, isodensity in 5, and punctate, streak and radial scars in 12. Except central scar, all lesions were markedly and homogeneously enhanced in the arterial phase. Nine of the 21 patients showed dilated and tortuous arteries in the central and peripheral areas of the focus. In the portal venous phase, focal density was decreased, though still higher or slightly higher in FNH than in parenchyma. In the delayed phase, the lesions showed isodensity or slight hypo- density. Enhanced capsules were seen in 3 patients. Dilated arteries and drainage veins were seen on an- giographic images. Conclusion: The characteristic manifestations of FNH on multiphasic helical CT scan are of great sig- nificance in diagnosing FNH and choosing viable therapy.

Percutaneous Microwave Coagulation for the Treatment of Small Solitary Focal Nodular Hyperplasia of Liver

Background: Whether percutaneous microwave coagulation (PMC) is safe and effective for the treatment of symptomatic focal nodular hyperplasia (FNH) of the liver remains unknown. Methods: Between January 2006 and September 2015, sixteen patients with solitary symptomatic FNHs in the liver (the largest diameter less than 5 cm) were treated by PMC. The safty and effectiveness were analyzed. Results: There were 4 males and 12 females. All these patients suffered from upper abdominal pain. The FNHs ranged in size from 3.2 cm to 5.0 cm (3.9 cm ± 0.12 cm). All the PMC procedures were performed successfully. All 16 patients had symptomatic improvement after the treatment with no procedure-related morbidity or mortality. Among 16 patients, 15 (93.8%) patients with FNHs were assessed to be ablated completely by CT examination performed within four weeks after PMC treatment. One patient failed to follow up regularly, but showed up 2 years and 7 months later for suffering upper abdominal pain again with original FNH enlargement, and the patient received surgical resection of the FNH and achieved asymptomatic aftermath. Conclusion: PMC is safe and effectiveness for symptomatic liver FNHs. PMC should be considered to be an alternative modality for those solitary FNHs with less than 5 cm in diameter.

A case of hepatocellular carcinoma arising within large focal nodular hyperplasia with review of the literature

Focal nodular hyperplasia （FNH） is a relatively rare benign hepatic tumor, usually presenting as a solitary lesion; however, multiple Iocalizations have also been described. The association of FNH with other hepatic lesions, such as adenomas and haemangiomas has been reported by various authors. We herein report a case of a hepatocellular carcinoma arising within a large focal nodular hyperplasia, in a young female patient.

Multi-parameter ultrasound based on the logistic regression model in the differential diagnosis of hepatocellular adenoma and focal nodular hyperplasia

BACKGROUND Focal nodular hyperplasia(FNH)has very low potential risk,and a tendency to spontaneously resolve.Hepatocellular adenoma(HCA)has a certain malignant tendency,and its prognosis is significantly different from FNH.Accurate identification of HCA and FNH is critical for clinical treatment.AIM To analyze the value of multi-parameter ultrasound index based on logistic regression for the differential diagnosis of HCA and FNH.METHODS Thirty-one patients with HCA were included in the HCA group.Fifty patients with FNH were included in the FNH group.The clinical data were collected and recorded in the two groups.Conventional ultrasound,shear wave elastography,and contrast-enhanced ultrasound were performed,and the lesion location,lesion echo,Young’s modulus(YM)value,YM ratio,and changes of time intense curve(TIC)were recorded.Multivariate logistic regression analysis was used to screen the indicators that can be used for the differential diagnosis of HCA and FNH.A ROC curve was established for the potential indicators to analyze the accuracy of the differential diagnosis of HCA and FNH.The value of the combined indicators for distinguishing HCA and FNH were explored.RESULTS Multivariate logistic regression analysis showed that lesion echo(P=0.000),YM value(P=0.000)and TIC decreasing slope(P=0.000)were the potential indicators identifying HCA and FNH.In the ROC curve analysis,the accuracy of the YM value distinguishing HCA and FNH was the highest(AUC=0.891),which was significantly higher than the AUC of the lesion echo and the TIC decreasing slope(P<0.05).The accuracy of the combined diagnosis was the highest(AUC=0.938),which was significantly higher than the AUC of the indicators diagnosing HCA individually(P<0.05).This sensitivity was 91.23%,and the specificity was 83.33%.CONCLUSION The combination of lesion echo,YM value and TIC decreasing slope can accurately differentiate between HCA and FNH.

Effect of fatty liver background on contrast-enhanced ultrasonographic appearance of focal nodular hyperplasia

BACKGROUND: Focal nodular hyperplasia (FNH) is increasingly diagnosed as a result of the advances in imaging studies such as contrast-enhanced ultrasonography (CEUS), enhanced computed tomography and magnetic resonance imaging. However, FNH with atypical features can be difficult to differentiate from other benign and malignant tumors. The aim of this study was to investigate the influence of fatty liver background on the CEUS characteristics of FNH. METHODS: Twenty-six patients with FNH were divided into two groups: group A included 14 patients with fatty liver and group B included 12 patients with normal liver background. Conventional two-dimensional ultrasonography and color Doppler flow imaging (CDFI) were conducted and followed by real-time dual-frame CEUS. RESULTS: On two-dimensional ultrasonography, hypoechoic nodules were present in most of the patients in group A (12/14) and hyperechoic nodules in most of those in group B (7/12). The difference in the nodule echotextures between the two groups was statistically significant (P<0.05). Nodules with centrifugal blood flow signals on CDFI were found in 6 of the 14 patients in group A and 5 of the 12 in group B (P>0.05). On CEUS, nodules with a central spoked-wheel-like enhancement pattern in the early arterial phase were observed in 8 patients in group A and those with an eccentric enhancement pattern in the remaining 6 patients. In this group, 3 patients had hypoechoic nodules in the delayed phase. Eleven of the 14 patients in this group were diagnosed accurately with CEUS. In group B, nodules with a rapid central spoked-wheel-like enhancement pattern in the early arterial phase were found in 8 patients by CEUS and those with rapid an eccentric enhancement pattern in 4. The nodules were found to be continuously enhanced in the delayed phase. All of the patients in group B were accurately diagnosed with CEUS. CONCLUSIONS: A FNH nodule on a background of fatty liver may present a hypoechoic pattern on two-dimensional ultrasonography and a hypoechoic wash-out pattern in the delayed phase on CEUS. At this time, punch biopsy is needed for the diagnosis or differential diagnosis of FNH.

Atypical CT and MRI Features of Focal Nodular Hyperplasia of Liver: A Study with Radiologic-Pathologic Correlation

Focal Nodular Hyperplasia (FNH) is the second most hepatic tumor next to hemangioma predominantly affecting women. It is a benign regenerative nodule having an unencapsulated well-defined mass with fibrovascular septae and proliferating bile ductules. Gadoxetic acid is a hepatocyte specific MR contrast agent which is known to be specific for the identifying FNH. Congenital vascular malformation and enlargement due to hormone stimulation is being considered as the main cause of FNH. The central stellate fibrovascular scar is a typical diagnostic imaging feature of FNH and the atypical pathological findings of FNH include large lesions multiple in number, internal necrosis, haemorrhagic foci and fatty infiltration. The atypical imaging features include non-enhancement of the central scar, calcification of the lesion, nonvisualized central scar and pseudocapsular enhancement on delayed imaging. For the accurate diagnosis of FNH, study of atypical radiologic features of FNH in correlation with pathological findings is the most essential. The macroscopic and the microscopic pathognomic changes should be taken as helpful points in the diagnosis of FNH. The main objective of this study is to recognize and understand the typical and atypical imaging patterns observed in CT and MR imaging of FNH with pathological correlation which avoids the necessity of biopsy and further investigations.

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 GadoliniumEOB-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.

Clonality and allelotype analyses of focal nodular hyperplasia compared with hepatocellular adenoma and carcinoma

AIM： To identify clonality and genetic alterations in focal nodular hyperplasia （FNH） and the nodules derived from it. METHODS： Twelve FNH lesions were examined. Twelve hepatocellular adenomas （HCAs） and 22 hepatocellular carcinomas （HCCs） were used as references. Nodules of different types were identified and isolated from FNH by microdissection. An X-chromosome inactivation assay was employed to describe their clonality status. Loss of heterozygosity （LOH） was detected, using 57 markers, for genetic alterations.RESULTS： Nodules of altered hepatocytes （NAH）, the putative precursors of HCA and HCC, were found in all the FNH lesions. Polyclonality was revealed in 10 FNH lesions from female patients, and LOH was not detected in any of the six FNH lesions examined, the results apparently showing their polyclonal nature. In contrast, monoclonality was demonstrated in all the eight HCAs and in four of the HCCs from females, and allelic imbalances were found in the HCAs （9/9） and HCCs （15/18）, with chromosomal arms 11p, 13q and 17p affected in the former, and 6q, 8p, 11p, 16q and 17p affected in the latter lesions in high frequencies （≥ 30%）. Monodonality was revealed in 21 （40%） of the 52 microdissected NAH, but was not found in any of the five ordinary nodules. LOH was found in all of the 13 NAH tested, being highly frequent at six loci on 8p, 11p, 13q and 17p. CONCLUSION： FNH, as a whole, is polyclonal, but some of the NAH lesions derived from it are already neoplastic and harbor similar allelic imbalances as HCAs.

Human immunodeficiency virus and nodular regenerative hyperplasia of liver: A systematic review

AIM: To investigate the diagnosis, pathogenesis, natural history, and management of nodular regenerative hyperplasia(NRH) in patients with human immunodeficiency virus(HIV). METHODS: We performed a systematic review of the medical literature regarding NRH in patients with HIV. Inclusion criteria include reports with biopsy proven NRH. We studied the clinical features of NRH, in particular, related to its presenting manifestation and laboratory values. Combinations of the following keywords were implemented: "nodular regenerative hyperplasia", "human immunodeficiency virus", "noncirrhotic portal hypertension", "idiopathic portal hypertension", "cryptogenic liver disease", "highly active antiretroviral therapy" and "didanosine". The bibliographies of these studies were subsequently searched for any additional relevant publications.RESULTS: The clinical presentation of patients with NRH varies from patients being completely asymptomatic to the development of portal hypertension – namely esophageal variceal bleeding and ascites. Liver associated enzymes are generally normal and synthetic function well preserved. There is a strong association between the occurrence of NRH and the use of antiviral therapies such as didanosine. The management of NRH revolves around treating the manifestations of portal hypertension. The prognosis of NRH is generally good since liver function is preserved. A high index of suspicion is required to make a identify NRH. CONCLUSION: The appropriate management of HIVinfected persons with suspected NRH is yet to be outlined. However, NRH is a clinically subtle condition that is difficult to diagnose, and it is important to be able to manage it according to the best available evidence.

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 mis-diagnosed 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.

Pictures of focal nodular hyperplasia and hepatocellular adenomas

This practical atlas aims to help liver and non liver pa-thologists to recognize benign hepatocellular nodules on resected specimen. Macroscopic and microscopic views together with immunohistochemical stains illustrate typical and atypical aspects of focal nodular hyperplasia and of hepatocellular adenoma, including hepatocel-lular adenomas subtypes with references to clinical and imaging data. Each step is important to make a correct diagnosis. The specimen including the nodule and the non-tumoral liver should be sliced, photographed and all different looking areas adequately sampled for par-affin inclusion. Routine histology includes HE, trichrome and cytokeratin 7. Immunohistochemistry includes glu-tamine synthase and according to the above results ad-ditional markers such as liver fatty acid binding protein, C reactive protein and beta catenin may be realized to differentiate focal nodular hyperplasia from hepatocel-lular adenoma subtypes. Clues for differential diagnosis and pitfalls are explained and illustrated.

Early- and intermediate-term outcome of transarterial embolization for symptomatic hepatic focal nodular hyperplasia

Purpose: To evaluate the early-and intermediate-term outcome in patients with symptomatic hepatic focal nodular hyperplasia(FNH) treated with transarterial embolization using bleomycin-iodinated oil and polyvinyl alcohol(PVA) particles. Materials and methods: In this two-center retrospective study between January 2005 and December 2013, 27 consecutive patients with symptomatic hepatic FNH underwent superselective catheterization by microcatheter techniques and embolization using bleomycin-iodinated oil combined with PVA. Early-term(3–41 months) follow-up of TAE was performed in terms of symptom control, changes in lesion size, and complications. Intermediate-term(45–112 months) follow-up was carried out to assess symptom control and reinterventions for recurrence. Results: Embolization was performed in 27 patients with 31 lesions. Technical success was achieved in all cases. The follow-up period ranged from three to 112 months. At early-term follow-up, mean lesion diameters were decreased significantly from 6.4±2.7 cm pre-intervention to 3.6±1.8 cm at 3-9 months after embolization(P<0.001). A total of 7 lesions had complete resolution during the whole follow-up period. At intermediate-term follow-up, local recurrence was found in 1 treated lesion at 54-months. Contrast-enhanced scans showed complete lack of residual arterial blood supply in the majority of lesions during the follow-up period. There was no major complication associated with the procedure. Conclusion: Transarterial embolization using bleomycin-iodinated oil and PVA is a feasible, safe and effective alternative in both early-and intermediate-terms for the treatment of symptomatic hepatic FNH.

Co-existence of hepatocellular adenoma and focal nodular hyperplasia in a young female

Focal nodular hyperplasia (FNH) and hepatocellular adenoma (HA) are both benign hepatocellular lesions, presenting mainly in women of childbearing age in non-cirrhotic, non-fibrotic livers. Simultaneous occurrence of these two lesions is extremely rare. We herein report a case of a young female without any predisposing risk factors who presented to our emergency department complaining of acute abdominal pain. Imaging studies revealed a 6 cm lesion in the right hepatic lobe and a 2.5 cm lesion in the left hepatic lobe, respectively. In view of the patient’s symptoms and lack of a confirmed diagnosis based on imaging, we performed a bisegmentectomy V-VI and a wedge resection of the lesion in segment III by laparotomy. Postoperative course was uneventful and the patient was discharged on the fourth postoperative day. The pathology report demonstrated an HA in segments V-VI and FNH in segment III, respectively. Six months later, the patient remains asymptomatic with normal liver function tests, ultrasound and magnetic resonance imaging follow-up. To our best knowledge, this is the first case to describe simultaneous occurrence of HA and FNH without the presence of any known risk factors for these entities. The uncertainty in diagnosis and acuteness of presenting symptoms were established criteria for prompt surgical intervention.

Focal nodular hyperplasia associated with a giant hepatocellular adenoma:A case report and review of literature

BACKGROUND Focal nodular hyperplasia(FNH)and hepatocellular adenoma(HCA)are wellknown benign liver lesions.Surgical treatment is usually chosen for symptomatic patients,lesions more than 5 cm,and uncertainty of diagnosis.CASE SUMMARY 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.CONCLUSION The simultaneous presence of benign composite liver tumors is rare.This case highlights the management in a multidisciplinary team setting.