Imaging characteristics of hypervascular focal nodular hyperplasialike lesions in patients with chronic alcoholic liver disease

BACKGROUND Focal nodular hyperplasia(FNH)-like lesions are hyperplastic formations in patients with micronodular cirrhosis and a history of alcohol abuse.Although pathologically similar to hepatocellular carcinoma(HCC)lesions,they are benign.As such,it is important to develop methods to distinguish between FNH-like lesions and HCC.AIM To evaluate diagnostically differential radiological findings between FNH-like lesions and HCC.METHODS We studied pathologically confirmed FNH-like lesions in 13 patients with alco-holic cirrhosis[10 men and 3 women;mean age:54.5±12.5(33-72)years]who were negative for hepatitis-B surface antigen and hepatitis-C virus antibody and underwent dynamic computed tomography(CT)and magnetic resonance imaging(MRI),including superparamagnetic iron oxide(SPIO)and/or gadoxetic acid-enhanced MRI.Seven patients also underwent angiography-assisted CT.RESULTS The evaluated lesion features included arterial enhancement pattern,washout appearance(low density compared with that of surrounding liver parenchyma),signal intensity on T1-weighted image(T1WI)and T2-weighted image(T2WI),central scar presence,chemical shift on in-and out-of-phase images,and uptake pattern on gadoxetic acid-enhanced MRI hepatobiliary phase and SPIO-enhanced MRI.Eleven patients had multiple small lesions(<1.5 cm).Radiological features of FNH-like lesions included hypervascularity despite small lesions,lack of“corona-like”enhancement in the late phase on CT during hepatic angiography(CTHA),high-intensity on T1WI,slightly high-or iso-intensity on T2WI,no signal decrease in out-of-phase images,and complete SPIO uptake or incomplete/partial uptake of gadoxetic acid.Pathologically,similar to HCC,FNH-like lesions showed many unpaired arteries and sinusoidal capillarization.CONCLUSION Overall,the present study showed that FNH-like lesions have unique radiological findings useful for differential diagnosis.Specifically,SPIO-and/or gadoxetic acid-enhanced MRI and CTHA features might facilitate differential diagnosis of FNH-like lesions and HCC.

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.

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.

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.

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.

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.

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.

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.

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.

Large focal nodular hyperplasia is unresponsive to arterial embolization: A case report

BACKGROUND Focal nodular hyperplasia(FNH)commonly occurs in women;it is usually asymptomatic and sometimes difficult to differentiate from hepatocellular carcinoma(HCC).CASE SUMMARY A large space-occupying lesion in the right lobe of the liver was incidentally detected in an adult man and diagnosed as HCC.Transcatheter arterial chemoembolization was applied once monthly for 2 years,but the lesion did not decrease in size.It was revealed by biopsy to be FNH.Eleven years later,the patient underwent liver resection due to hemorrhage and the pathological examination confirmed FNH.CONCLUSION For a space-occupying lesion,it is prerequisite to pathologically confirm the diagnosis and the corresponding intervention can be effective.

Hepatic focal nodular hyperplasia in children:Imaging features on multi-slice computed tomography

AIM:To retrospectively analyze the imaging features of hepatic focal nodular hyperplasia(FNH) in children on dynamic contrast-enhanced multi-slice computed tomography(MSCT) and computed tomography angiography(CTA) images.METHODS:From September 1999 to April 2012,a total of 218 cases of hepatic FNH were confirmed by either surgical resection or biopsy in the Sun Yat-sen Memorial Hospital of Sun Yat-sen University and the Cancer center of Sun Yat-sen University,including 12 cases(5.5%) of FNH in children(age ≤ 18 years old).All the 12 pediatric patients underwent MSCT.We retrospectively analyzed the imaging features of FNH lesions,including the number,location,size,margin,density of FNH demonstrated on pre-contrast and contrastenhanced computed tomography(CT) scanning,central scar,fibrous septa,pseudocapsule,the morphology of the feeding arteries and the presence of draining vessels(portal vein or hepatic vein).RESULTS:All the 12 pediatric cases of FNH had solitary lesion.The maximum diameter of the lesions was 4.0-12.9 cm,with an average diameter of 5.5 ± 2.5 cm.The majority of the FNH lesions(10/12,83.3%) had well-defined margins.Central scar(10/12,83.3%) and fibrous septa(11/12,91.7%) were commonly found in children with FNH.Central scar was either isodense(n = 7) or hypodense(n = 3) on pre-contrast CT images and showed progressive enhancement in 8 cases in the equilibrium phase.Fibrous septa were linear hypodense areas in the arterial phase and isodense in the portal and equilibrium phases.Pseudocapsule was very rare(1/12,8.3%) in pediatric FNH.With the exception of central scars and fibrous septa within the lesions,all 12 cases of pediatric FNH were homogenously enhanced on the contrast-enhanced CT images,significantly hyperdense in the arterial phase(12/12,100.0%),and isodense in the portal venous phase(7/12,58.3%) and equilibrium phase(11/12,91.7%).Central feeding arteries inside the tumors were observed on CTA images for all 12 cases of FNH,whereas no neovascularization of malignant tumors was noted.In 9 cases(75.0%),there was a spoke-wheel shaped centrifugal blood supply inside the tumors.The draining hepatic vein was detected in 8 cases of pediatric FNH.However,the draining vessels in the other 4 cases could not be detected.No associated hepatic adenoma or hemangioma was observed in the livers of the 12 pediatric cases.CONCLUSION:The characteristic imaging appearances of MSCT and CTA may reflect the pathological and hemodynamic features of pediatric FNH.Dynamic multi-phase MSCT and CTA imaging is an effective method for diagnosing FNH in children.

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.

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.

Research on focal nodular hyperplasia with MSCT and postprocessing

AIM： To investigate and evaluate the pathological features and diagnostic value of focal nodular hyperplasia （FNH） with multiection spiral computed tomography （MSCT） and postprocessing. METHODS： A total of 25 patients with FNH who had undergone MSCT and postprocessing were included in the investigation. All patients had been pathologically or clinically confirmed with FNH. A number of 75 cases of hepatic carcinomas, hemangiomas and adenomas were randomly selected at a same period for a comparative study. RESULTS： There was a single focus in 22 cases and multiple foci in 3 cases. On the plain scan, 17 lesions showed hypodensity, 7 isodensity and 4 hyperdensity （the case with fatty liver）. With contrast, 28 lesions were enhanced evenly or in the nodules in the arterial phase; 13 lesions still showed hyperdensity, 11 lesions isodensity and 4 lesions hypodensity in the parenchymatous phase; in the delayed phase only 5 lesions showed hyperdensity but 9 lesions showed isodensity or slight hypodensity and 14 lesions showed hypodensity. Twelve lesions of 28 had central asteroid scars. Thickened feeding arteries in postprocessing were seen in 24 lesions, and were integrated into the parenchymatous lesions with a gradual and smooth course. On the contrary, there were no artery penetrated into the lesion found in any of comparative hepatic tumors. CONCLUSION： Doctors could make a correct diagnosis and differentiation of FNH on evaluation of the characteristic appearance on MSCT with postprocessing,

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.

Focal nodular hyperplasia with concomitant hepatocellular carcinoma: a case report and clonal analysis

This report describes a hepatocellular carcinoma (HCC) with concomitant focal nodular hyperplasia (FNH) in a 56 years old Chinese man. There were two well circumscribed tumours measuring 3×2.5×2 cm and 2×1.5×1.5 cm. The larger mass was grey and soft with a small area of bleeding and necrosis and an intact capsule. The smaller mass was yellow and had no capsule. Clonal analysis was carried out to clarify the relation between the HCC and the adjacent FNH. The clonal analysis was based on the methylation pattern of the polymorphic X chromosome linked androgen receptor gene (HUMARA). In FNH, after Hpa Ⅱ digestion, the allelic bands showed two well defined peaks. The intensity of the two peaks in the DNA from cirrhotic tissue did not differ significantly, consistent with a random pattern of X chromosome inactivation. However, in HCC, after Hpa Ⅱ digestion, the allelic bands differed significantly in intensity. Therefore, there was a typical polyclonal pattern of inactivation in FNH but the HCC was interpreted as being monoclonal.