Focal Nodular Hyperplasia in the Pediatric Population: A Multicenter Experience.

BACKGROUND: Focal nodular hyperplasia (FNH) is a benign liver lesion classically presenting in young females. In children, FNH is rare and its detailed clinicopathologic characteristics remain largely unknown. Furthermore, there are no studies comparing pediatric FNH features to those presenting in adults. METHODS: In this study, we analyzed a total of 47 FNH cases in pediatric patients (age range: 23 days to 18 years) from 3 centers and compared them to a cohort of 31 FNH cases in adult patients (age range: 20-64 years). RESULTS: Of the pediatric cases, 13 cases (28%) had a history of a prior malignancy of which 4 were treated with chemoradiation and stem cell transplantation (SCT), 5 with chemoradiation alone and 3 with chemotherapy and SCT. In the pediatric cases 41 (87%) had a central scar and 46 (98%) had fibrous septa. Both pediatric and adult FNH were more common in female patients. Cases in pediatric patients were also significantly associated with larger size (P = .047), absence of dystrophic vessels (P = .001), absence of sinusoidal dilatation (P = .029), pseudoacini formation (P = .013), and steatosis (P = .029). CONCLUSION: In our experience although most cases of pediatric FNH show the classic histologic features seen in adults, some significant differences exist, and awareness of these findings could aid in the evaluation of these rare cases.

Hepatic involvement in hereditary hemorrhagic telangiectasia mimicking focal nodular hyperplasia.

Accurate diagnosis of hereditary hemorrhagic telangiectasia (HHT), also known as Rendu-Osler-Weber disease, is important for reducing the risk of complications. Hepatic involvement in HHT is usually asymptomatic, but when present can cause noted morbidity and mortality. A 62-year-old woman presented with moderate upper-abdominal pain and tachycardia. A diagnosis of HHT was made based on the findings of hepatic involvement in a contrast-enhanced abdominal computed tomography (CT) scan, the presence of arteriovenous malformations (AVMs; a.k.a. telangiectasias) on mucocutaneous surfaces, and a history of recurrent epistaxis. Imaging methods are important diagnostic tools in patients suspected of having HHT.

Focal Nodular Hyperplasia and Focal Nodular Hyperplasia-like Lesions.

Focal nodular hyperplasia (FNH) is a benign lesion occurring in a background of normal liver. FNH is seen most commonly in young women and can often be accurately diagnosed at imaging, including CT, MRI, or contrast-enhanced US. In the normal liver, FNH frequently must be differentiated from hepatocellular adenoma, which although benign, is managed differently because of the risks of hemorrhage and malignant transformation. When lesions that are histologically identical to FNH occur in a background of abnormal liver, they are termed FNH-like lesions. These lesions can be a source of diagnostic confusion and must be differentiated from malignancies. Radiologists' familiarity with the imaging appearance of FNH-like lesions and knowledge of the conditions that predispose a patient to their formation are critical to minimizing the risks of unnecessary intervention for these lesions, which are rarely symptomatic and carry no risk for malignant transformation. FNH is thought to form secondary to an underlying vascular disturbance, a theory supported by the predilection for formation of FNH-like lesions in patients with a variety of hepatic vascular abnormalities. These include abnormalities of hepatic outflow such as Budd-Chiari syndrome, abnormalities of hepatic inflow such as congenital absence of the portal vein, and hepatic microvascular disturbances, such as those that occur after exposure to certain chemotherapeutic agents. Familiarity with the imaging appearances of these varied conditions and knowledge of their association with formation of FNH-like lesions allow radiologists to identify with confidence these benign lesions that require no intervention. Online supplemental material is available for this article. ©RSNA, 2022.

Regenerative nodular hyperplasia, portal vein thrombosis and primary myelofibrosis: an unusual triple association.

We report a case of a regenerative nodular hyperplasia with a portal vein cavernomatosis with a subsequent progression to symptomatic, occlusive thrombosis of the superior mesenteric vein. A thorough investigation resulted in a final diagnosis of primary myelofibrosis associated with the V617F mutation in the JAK2 gene.

What is Changing in Indications and Treatment of Focal Nodular Hyperplasia of the Liver. Is There Any Place for Surgery?

Focal nodular hyperplasia (FNH) is a common benign liver tumor, which occurs in the vast majority of the cases in young women. FNH represents a polyclonal lesion characterized by local vascular abnormalities and is a truly benign lesion without any potential for malignant transformation. A retrospective single institution analysis of 227 FNH patients, treated from 1990 to 2016 and a review of studies reporting surgical therapy of overall 293 patients with FNH was performed. Indications for resection with a focus on diagnostic workup, patient selection, surgical mode and operative mortality and morbidity have been analysed. Ninety three patients underwent elective hepatectomy and 134 patients observation alone, where median follow-up was 107 months. Postoperative complications were recorded in 14 patients, 92% of patients reported an improvement with respect to their symptoms. Overall among 293 patients underwent surgery in the series, included to this review, there was a morbidity of 13%, where median follow-up was 53 months. Systematic follow-up remains the gold standard in asymptomatic patients with FNH. However elective surgery should be considered in symptomatic patients, in those with marked enlargement and in case of uncertainty of diagnosis. Surgery for FNH is a safe procedure with low morbidity and very good long term results as far as quality of life after surgery is concerned and surely an integral part of the modern management of FNH.

Drug-induced nodular regenerative hyperplasia.

Drug-induced nodular regenerative hyperplasia is an uncommon injury with unique pathophysiology, clinical, and diagnostic considerations. This injury is characteristically asymptomatic in its early phases with only mild elevations in transaminases (< 3× upper limit of normal [ULN]). The latency period is typically more than 6 months. Once clinically apparent, it is marked by complications of portal hypertension, including hypersplenism, ascites, and variceal bleeding, with little or no hepatic dysfunction. Hence, it is an important cause of noncirrhotic portal hypertension. The most commonly associated drugs include thiopurines, chemotherapeutic agents, and antiretroviral agents. Diagnosis is aided by the recognition of noncirrhotic portal hypertension, a detailed history of prior drug exposure, and exclusion of the other causes of nodular regenerative hyperplasia. Clinical history, abdominal imaging, and hepatic hemodynamic studies provide important diagnostic clues, but histologic examination remains the diagnostic gold standard. Therapeutic intervention is aimed at earliest discontinuation of the offending agent and of portal hypertension complications. The natural history varies widely, and portal hypertension can progresses despite drug discontinuation.

Downregulation of the endothelial genes Notch1 and ephrinB2 in patients with nodular regenerative hyperplasia.

BACKGROUND & AIMS: Nodular regenerative hyperplasia (NRH) is a rare liver disease characterized by small regenerative nodules without fibrosis and can cause portal hypertension. Aetiology and pathogenesis of NRH remain unclear. We have recently shown that Notch1 knockout induces NRH with portal hypertension through vascular remodelling in mice. The aim of this study was to analyse histological and clinical data of NRH patients and to explore if the endothelial pathways identified in our NRH mouse model are also regulated in human NRH. METHODS: Patients were identified retrospectively from the pathology database. Clinical and laboratory patient data were retrieved. mRNA expression was measured in liver biopsies from a subset of NRH patients. RESULTS: Diagnosis of NRH was confirmed in needle biopsies of 51 patients, including 31 patients with grade 1, 12 patients with grade 2 and 8 patients with grade 3 NRH. Grade 3 nodularity significantly correlated with the presence of portal hypertension: 50% of the patients with grade 3 NRH vs. 6.5% with grade 1 (P = 0.0105). mRNA expression analysis in liver biopsies from 14 NRH patients and in primary human sinusoidal endothelial cells revealed downregulation of identical genes as in the murine NRH model, which are implicated in vascular differentiation: Notch1, delta-like 4 (Dll4) and ephrinB2. CONCLUSIONS: In this large NRH needle biopsy cohort, we demonstrated that advanced nodularity correlates with presence of portal hypertension. Downregulation of the endothelial signalling pathways Dll4/Notch1 and ephrinB2/EphB4 supports the hypothesis that human NRH is caused by a sinusoidal injury providing first insights into the molecular pathogenesis of this liver condition.

Focal nodular hyperplasia within accessory liver: imaging findings at computed tomography and magnetic resonance imaging.

Accessory liver tissue is a rare but probably underreported entity that may harbor the same spectrum of pathology as that of the parent organ. The rarity and aberrant locations of such lesions cause confusion and may lower diagnostic confidence despite otherwise classic radiographic appearances. Focal nodular hyperplasia (FNH) is the most common non-hemangiomatous benign hepatic tumor, but to our knowledge, ectopic FNH has been reported only once before in the gastroenterology literature. We present the first case of ectopic FNH in the radiology literature.

Nodular regenerative hyperplasia of the liver and cutaneous T-cell lymphoma: an unreported association.

Nodular regenerative hyperplasia of the liver -a type of noncirrhotic portal hypertension- is a rare condition of unknown etiopathogenesis that has been associated with multiple disorders, including diverse types of hematologic disease. We report the case of a 36-year-old female patient diagnosed with cutaneous T-cell lymphoma of the mycosis fungoides variety, staged as T2N0M0B0, where a transjugular liver biopsy demonstrated the presence of nodular regenerative hyperplasia with a hepatic venous pressure gradient of 15 mm Hg. The study was triggered by the incidental radiologic finding of hepatomegaly with indirect evidence of portal hypertension. We are not aware of any previous reports on the association of nodular regenerative hyperplasia with mycosis fungoides in the medical literature.

Patient with a novel syndrome with multiple benign hepatic lesions and extrahepatic neoplasms.

Simultaneous occurrence of benign hepatic lesions of different types is a sporadic phenomenon. To the best of our knowledge, we report the first clinical case of a syndrome with simultaneous manifestations of three different entities of benign liver tumors (hepatocellular adenoma, focal nodular hyperplasia and hemangioma) with a novel mutation detected in the liver adenoma and in the presence of a number of further extrahepatic organ neoplasms. Furthermore, we describe for the first time the presence of liver epithelial cells of hepatocytic phenotype expressing cytokeratin 7 (CK7) at the border of the adenoma. These findings may be important for explaining pathogenesis of benign as well as malignant tumors based on genetic and histopathological features.

An Splenic Artery Aneurysm and Focal Nodular Hyperplasia Associated with an Abdominal Vascular Abnormality of Hereditary Hemorrhagic Telangiectasia.

In October 2021, a 51-year-old woman developed a skin rash. Abdominal computed tomography revealed a large splenic artery aneurysm and an intrahepatic portovenous shunt. As her splenic artery aneurysm was at risk of rupture, she was referred to the Kindai University Hospital and underwent coiling surgery. In October 2023, approximately two years after she had been initially referred, contrast-enhanced ultrasound revealed findings suggestive of focal nodular hyperplasia. No reports have confirmed the occurrence of liver masses in patients with hereditary hemorrhagic telangiectasia, which is considered to be an interesting finding when investigating the mechanism of tumor development.

MR findings of steatotic focal nodular hyperplasia and comparison with other fatty tumours.

OBJECTIVES: To correlate MR findings with pathology in steatotic FNHs and to compare the MR findings with those of other fatty tumours developed on noncirrhotic liver in a consecutive series of resected lesions. METHODS: Our population included resected FNH with intralesional steatosis (n = 25) and other resected fatty tumours selected as controls (hepatocellular adenomas and angiomyolipomas, n = 34). Lesions were classified into three groups: those with typical FNH without (group 1) or with (group 2) fat on MR and those with atypical lesions (group 3). In group 3, diagnostic criteria for other fatty tumours were applied. RESULTS: There were 9 lesions in group 1 (15.3 %), 4 in group 2 (16.8 %) and 46 in group 3 (77.9 %). Group 3 contained 12 FNHs (26 %) and all the other fatty tumours. In group 3, the association of lesion homogeneity, signal intensity similar to or slightly different from adjacent liver on in-phase T1- and T2-weighted sequences, and strong arterial enhancement was observed in 7/12 (58 %) of steatotic FNHs and 3/34 (9 %) of other tumours. CONCLUSION: On MR, fat within a typical FNH should not reduce the diagnostic confidence. We recommend further investigations including liver biopsy if necessary when fatty tumours exhibit atypical MR findings.

No evidence of substantial growth progression or complications of large focal nodular hyperplasia during pregnancy.

OBJECTIVE: Focal nodular hyperplasia (FNH) is a benign liver tumor considered to develop under the influence of estrogens. Whether women with known FNH are at higher risk of growth progression and complications during pregnancy is still controversially discussed. The authors investigated the growth pattern of FNH during pregnancy and possible related complications. MATERIALS AND METHODS: Twenty pregnant women with FNH were followed by the authors' center. Before pregnancy, diagnosis of FNH was usually established by contrast-enhanced ultrasound. During pregnancy, monitoring of FNH was performed by conventional ultrasound. Furthermore, a questionnaire was sent to all patients. RESULTS: Patient's age ranged from 24 to 36 years. Mean size of FNH before pregnancy was 58.5 ± 22.7 mm. It did not vary significantly during pregnancy (fourth month of pregnancy: 58.1 ± 23.0 mm; after pregnancy: 55.5 ± 26.8 mm; -8%; n.s.). Only in three patients, growth of FNH by 18 ± 6% was observed, while FNH size remained constant in 7 patients and even declined by -11 ± 6% in 10 patients. There were no FNH-related complications. The questionnaire was sent back by 16 patients (80%). All responding patients took oral contraceptives in the past over a mean 12.4 ± 4.4 years. Previous pregnancies were reported by 38% of patients. FNH-related fears were expressed by 63% of patients, but no FNH-related complications or symptoms during pregnancy were noted. CONCLUSIONS: This study demonstrates that women with FNH are not at risk of significant growth progression or FNH-related complications. Pregnancy should not be discouraged in these patients but careful advice and guidance are necessary.

Congenital portosystemic shunts associated with liver tumours.

AIM: To evaluate the diagnosis and presentation of liver tumours in patients with congenital portosystemic shunts (CPS). MATERIALS AND METHODS: Eight patients were diagnosed in Hôpital Beaujon as having CPS. All patients underwent Doppler ultrasound, computed tomography (CT), magnetic resonance imaging (MRI), and histological examination of liver tumours. CPS were classified according to anatomy and the amount of portal flow deviated to the systemic circulation as: total, subtotal, or partial. Liver tumours were diagnosed by needle core biopsy (n = 5) or surgery (n = 3). Clinical follow-up was available in all patients but one (mean follow-up 36 months; range 1-5 years). RESULTS: Six patients had total CPS, one patient had a subtotal CPS, and the last had a partial CPS. All patients presented with multiple liver nodules (range four to >15). The tumours were characterized as focal nodular hyperplasia (FNH; n = 4), FNH with hepatocellular adenoma (n = 2), and regenerative nodular hyperplasia (n = 2). In four of seven patients (57%) that had follow-up, tumours showed enlargement or new lesions appeared. CONCLUSION: In this series of CPS patients, tumours were all benign, multiple, and of hepatocellular origin, and different tumours were present simultaneously in two patients. Tumour enlargement or new nodules were common during follow-up.

Focal liver lesion classification and characterization in noncirrhotic liver: a prospective comparison of diffusion-weighted magnetic resonance-related parameters.

PURPOSE: The objective of this study was to prospectively verify if diffusion-weighted magnetic resonance (DwMR)-related parameters such as perfusion fraction (f) and slow diffusion coefficient (D), according to Le Bihan theory, are more effective than apparent diffusion coefficient (ADC) for classification and characterization of the more frequent focal liver lesions (FLLs) in noncirrhotic liver. METHODS: Sixty-seven patients underwent standard liver magnetic resonance imaging (MRI) and free-breath multi-b DwMR study. Two regions of interest were defined by 2 observers, including 1 FLL for each patient (21 hemangiomas, 21 focal nodular hyperplasias, 25 metastases) and part of surrounding parenchyma, respectively. For every FLL, D, f, and ADC were estimated both as absolute value and as ratio between FLL and surrounding parenchyma by fitting the reduced equation of the bicompartmental model to experimental data; t test, analysis of variance, and receiver operating characteristic analysis were performed. RESULTS: t Test showed significant differences in ADClesion, f lesion, D lesion, ADCratio, and D ratio values between benign and malignant FLLs, more pronounced for ADClesion (P < 0.0009) and ADCratio (P = 0.001). Applying cutoff values of 1.55 × 10 mm/s (ADClesion) and 0.89 (ADCratio), the DwMR study presented sensitivities and specificities, respectively, of 84% and 80% (for ADClesion), 72% and 80% (ADCratio). CONCLUSIONS: Apparent diffusion coefficient (by fitting procedures) better performs than do D and f in FLL classification, especially when its values are less than 1.30 or greater than 2.00 × 10 mm/s.

Hepatocellular adenoma in glycogen storage disorder type I: a clinicopathological and molecular study.

AIMS: Glycogen storage disease type I is a metabolic disorder resulting from deficiency of the glucose-6-phosphate complex. Long-term complications include the development of hepatocellular adenoma (HCA). In this retrospective study, our aim was to reclassify according to geno-phenotypic characteristics nodular lesions identified in hepatectomy specimens of such patients transplanted between 1998 and 2008 at our institution. METHODS AND RESULTS: Clinicopathological data of seven consecutive transplanted patients with glycogen storage disease type I were reviewed. Liver nodules were re-examined histologically and by immunohistochemistry. Molecular analysis was performed additionally in a case with specific features. Four patients had multiple tumours. We concluded that 26 of 38 nodules available for study had features of inflammatory hepatocellular adenomas, seven comprised adenomas not otherwise specified and five were found to be focal nodular hyperplasia. CONCLUSIONS: Further studies are needed to clarify the pathogenesis of hepatocellular adenomas in glycogen storage disease; in particular to determine whether they share abnormal metabolic pathways with inflammatory adenomas in the general population. Testing for acute phase proteins may be a helpful tool in the early detection of HCA in such patients. Finally, there is a need to further define their risk of malignant transformation, in relation to age and possible cofactors.

Liver transplantation for refractory severe pruritus related to widespread multifocal hepatic focal nodular hyperplasia (FNH) in a child: case report and review of literature.

FNH is a rare and benign tumor of the liver. It is not a conventional indication for liver transplantation, and no transplant for FNH in a child has been reported to date. Multifocal FNH growing in adolescent age to a widespread tumor invading the whole liver and associated with severe refractory pruritus was an unusual indication for transplantation in a 13-yr-old girl. The operation and the follow-up were uneventful, allowing full recovery and disappearance of pruritus.