Liver cell adenoma:A case report with clonal analysis and literature review

We report a case of liver cell adenoma （LCA） in a 33-year-old female patient with special respect to its clonality status, pathogenic factors and differential diagnosis. The case was examined by histopathology, immunohistochemistry and a clonality assay based on X-chromosomal inactivation mosaicism in female somatic tissues and polymorphism at androgen receptor focus. The clinicopathological features of the reported cases from China and other countries were compared. The lesion was spherical, sizing 2 cm in its maximal dimension. Histologically, it was composed of cells arranged in cords, most of which were two-cell-thick and separated by sinusoids. Focal fatty change and excessive glycogen storage were observed. The tumor cells were round or polygonal in shape, resembling the surrounding parenchymal cells. Mitosis was not found. No portal tract, central vein or ductule was found within the lesion. The tumor tissue showed a positive reaction for cytokeratin （CK） 18, but not for CK19, vimentin, estrogen and progesterone receptors. Monoclonality was demonstrated for the lesion, confirming the diagnosis of an LCA. Clonality analysis is helpful for its distinction from focal nodular hyperplasia.K

Liver cell adenoma showing sequential alteration of radiological findings suggestive of well-differentiated hepatocellular carcinoma

A liver tumor 35 mm in diameter was found incidentally in a 40-year-old woman who had no history of liver diseases or the use of oral contraceptives.Radiological diagnostics showed the typical findings of liver cell adenoma(LCA).Dynamic computed tomography revealed that the tumor showed a homogenous enhancement in the arterial phase and almost the same enhancement as the surrounding liver parenchyma in the delayed phase.The tumor was found to contain fat on magnetic resonance imaging.A benign fat containing liver tumor was suggested.However,radiological findings altered,which caused us to suspect that a welldifferentiated hepatocellular carcinoma(HCC)containing fat was becoming dedifferentiated.Partial hepatectomy was performed and the pathological findings showed the typical findings of LCA.This case was an extremely rare LCA,which had no background of risk for LCA and developed the sequential alteration of the radiological findings to suspect well-differentiated HCC.

Liver cell adenoma with malignant transformation:A case report

A 57-year-old woman was referred to our hospital because of a liver mass detected by computed tomography.She had taken oral contraceptives for only one month at the age of thirty.Physical examination revealed no abnormalities,and laboratory data,including hepatic function tests,were within the normal range,with the exception of elevated levels of those serum proteins induced by the absence of vitamin K or by raised levels of the antagonist (PIVKA)-Ⅱ (3 502 AU/ml). Abdominal ultrasonography revealed a hyperechoic mass measuring 10×10 cm in the left posterior segment of the liver.Because hepatocellular carcinoma could not be completely excluded,this mass was resected.The tumor consisted of sheets of uniform cells with clear cytoplasm, perinuclear eosinophilic granules and round nuclei.These histological findings were consistent with liver cell adenoma. Background hepatic tissue appeared normal.After resection of the tumor,serum PIVKA-Ⅱ fell to within the normal range. An area of hepatocellular carcinoma (HCC) with a mid- trabecular pattern was immunohistochemically found,which was positive for PIVKA-Ⅱ.Sinusoidal endothelial cells were CD34-positive,containing scattered PIVKA-Ⅱ positive cells. This tumor was therefore finally diagnosed as liver cell adenoma with focal malignant transformation to HCC.

Predicting colorectal adenomatous polyps in patients with chronic liver disease: A novel nomogram

BACKGROUND Colorectal polyps are commonly observed in patients with chronic liver disease(CLD)and pose a significant clinical concern because of their potential for malignancy.AIM To explore the clinical characteristics of colorectal polyps in patients with CLD,a nomogram was established to predict the presence of adenomatous polyps(AP).METHODS Patients with CLD who underwent colonoscopy at Tianjin Second People’s Hospital from January 2020 to May 2023 were evaluated.Clinical data including laboratory results,colonoscopy findings,and pathology reports were collected.Key variables for the nomogram were identified through least absolute shrinkage and selection operator regression,followed by multivariate logistic regression.The performance of the model was evaluated using the area under the receiver area under curve,as well as calibration curves and decision curve analysis.RESULTS The study enrolled 870 participants who underwent colonoscopy,and the detection rate of AP in patients with CLD was 28.6%.Compared to individuals without polyps,six risk factors were identified as predictors for AP occurrence:Age,male sex,body mass index,alcohol consumption,overlapping metabolic dysfunction-associated steatotic liver disease,and serum ferritin levels.The novel nomogram(AP model)demonstrated an area under curve of 0.801(95%confidence interval:0.756-0.845)and 0.785(95%confidence interval:0.712-0.858)in the training and validation groups.Calibration curves indicated good agreement among predicted and actual probabilities(training:χ^(2)=11.860,P=0.157;validation:χ^(2)=7.055,P=0.530).The decision curve analysis underscored the clinical utility of the nomogram for predicting the risk of AP.CONCLUSION The AP model showed reasonable accuracy and provided a clinical foundation for predicting the occurrence of AP in patients with CLD,which has a certain predictive value.

Two-stage liver transplant for ruptured hepatic adenoma:A case report

BACKGROUND Only one case of liver transplantation for hepatic adenoma has previously been reported for patients with rupture and uncontrolled hemorrhage.We present the case of a massive ruptured hepatic adenoma with persistent hemorrhagic shock and toxic liver syndrome which resulted in a two-stage liver transplantation.This is the first case of a two-stage liver transplantation performed for a ruptured hepatic adenoma.CASE SUMMARY A 23 years old African American female with a history of pre-diabetes and oral contraceptive presented to an outside facility complaining of right-sided chest pain and emesis for one day.She was found to be in hemorrhagic shock due to a massive ruptured hepatic hepatic adenoma.She underwent repeated embolizations with interventional radiology with ongoing hemorrhage and the development of renal failure,hepatic failure,and hemodynamic instability,known as toxic liver syndrome.In the setting of uncontrolled hemorrhage and toxic liver syndrome,a hepatectomy with porto-caval anastomosis was performed with liver transplantation 15 h later.She tolerated the anhepatic stage well,and has done well over one year later.CONCLUSION When toxic liver syndrome is recognized,liver transplantation with or withouthepatectomy should be considered before the patient becomes unstable.

Hepatocellular adenoma: An unsolved diagnostic enigma

Hepatocellular adenoma (HCA) is a rare benign liver tumour associated with the use of oral contraceptives or other steroid medications which occurs predominantly in young and middle-aged women. Unlike other benign liver tumours, an HCA may be complicated by bleeding and malignant transformation. HCAs have been divided into four subtypes based on molecular and pathological features: hepatocyte nuclear factor 1α-mutated HCA, inflammatory HCA,β-catenin-mutated HCA, and unclassified HCA.β-cateninmutated HCA has the highest risk of haemorrhage or malignant transformation. In the latest upgrade of the guidelines regarding the management of benign liver tumours published in 2016 by the European Association for the Study of the Liver, magnetic resonance imaging (MRI) was recognized to be superior to all other imaging modalities in detecting HCAs and in being able to subtype HCAs up to 80%, with positive identification of 1α-mutated HCA or inflammatory HCA achievable with > 90% specificity. This review analyzed the imaging features of HCA using MRI with hepato-specific contrast agents, focusing on the limitations in the HCA characterization.

Hepatocellular adenoma: An update

Hepatocellular adenomas(HCA) are rare benign liver tumors.Recent technological advancements have helped in the early identification of such lesions.However,precise diagnosis of hepatocellular incidentalomas remains challenging.Studies at the molecular level have provided new insights into the genetics and pathophysiology of these lesions.These in turn have raised questions over their existing management modalities.However,the rarity of the tumor still restricts the quality of evidence available for current recommendations and guidelines.This article provides a comprehensive review on the etiology,molecular biology,pathophysiology,clinical manifestations,and complications associated with HCA.It also elaborates on the genetic advancements,existing diagnostic tools and current guidelines for management for such lesions.

Hepatocytic differentiation of mesenchymal stem cells in cocultures with fetal liver cells

AIM： To investigate the hepatocytic differentiation of mesenchymal stem cells （MSCs） in co-cultures with fetal liver cells （FLC） and the possibility to expand differentiated hepatocytic cells. METHODS： MSCs were marked with green fluorescent protein （GFP） by retroviral gene transduction. Clonal marked MSCs were either cultured under liver stimulating conditions using fibronectin-coated culture dishes and medium supplemented with stem cell factor （SCF）, hepatocyte growth factor （HGF）, epidermal growth factor （EGF）, and fibroblast growth factor 4 （FGF-4） alone, or in presence of freshly isolated FLC. Cells in co-cultures were harvested, and GFP＋ or GFP- cells were separated using fluorescence activated cell sorting. Reverse transcription-polymerase chain reaction （RT-PCR） for the liver specific markers cytokeratin-18 （CK-18）, albumin, and alpha-fetoprotein （AFP） was performed in different cell populations. RESULTS- Under the specified culture conditions, rat MSCs co-cultured with FLC expressed albumin, CK-18, and AFP-RNA over two weeks. At wk 3, MSCs lost hepatocytic gene expression, probably due to overgrowth of the cocultured FLC. FLC also showed a stable liver specific gene expression in the co-cultures and a very high growth potential. CONCLUSION： The rat MSCs from bone marrow can differentiate hepatocytic cells in the presence of FLC in vitro and the presence of MSCs in co-cultures also prorides a beneficial environment for expansion and differentiation of FLC.

Management of hepatocellular adenoma: Solitary-uncomplicated, multiple and ruptured tumors

AIM： While hepatocellular adenomas （HAs） have often been studied as a unique entity, we aimed to better define current management of the various forms of HAs. METHODS： Twenty-five consecutive patients operated for solitary-uncomplicated （9）, multiple （6）, and ruptured （10） HAs were reviewed according to management strategies and outcomes. RESULTS： All solitary-uncomplicated HAs （ranged 2.2- 14 cm in size） were removed. Out of 25 HAs, 2 （8%） included loci of carcinoma. In the multiple HA group, previously undiagnosed tumors were identified during surgery in 5/6 cases. In three cases with multiple spread HA, several lesions had to be left unresected. They remained unmodified after 4-, 6-, and 6-year radiological follow-up. Patients with ruptured HA （ranged 1.7-10 cm in size） were initially managed with hemodynamic support and angiography, allowing the embolizaUon of actively bleeding tumors in two patients. All ruptured tumors were subsequently removed 5.5 d （range 4-70 d） after admission. CONCLUSION： Tumors suspected of HA, regardless of the size, should be resected, because of high chances of rupture causing bleeding, and/or containing malignant foci. Although it is desirable to remove all lesions of multiple HA, this may not be possible in some patients, for whom long-term radiological follow-up is advised. Ruptured HA can be managed by hemodynamic support and angiography, allowing scheduled surgery. 2005 The WJG Press and Elsevier Inc. All rights reserved

Comparative study on radiosensitivity of various tumor cells and human normal liver cells

AIM:To investigate the radiation response of various human tumor cells and normal liver cells. METHODS: Cell lines of human hepatoma cells (SMMC-7721), liver cells (L02), melanoma cells (A375) and cervical tumor (HeLa) were irradiated with 60Co γ-rays. Cell survive was documented by a colony assay. Chromatid breaks were measured by counting the number of chromatid breaks and isochromatid breaks immediately after prematurely chromosome condensed by Calyculin-A. RESULTS: Linear quadratic survival curve was observed in all of four cell lines, and dose-dependent increase in radiation-induced chromatid and isochromatid breaks were observed in GB2B phase. Among these four cell lines, A375 was most sensitive to radiation, while, L02 had the lowest radiosensitivity. For normal liver cells, chromatid breaks were easy to be repaired, isochromatid breaks were difficult to be repaired. CONCLUSION: The results suggest that the y-rays induced chromatid breaks can be possibly used as a good predictor of radiosensitivity, also, unrejoined isochromatid breaks probably tightly related with cell cancerization.

Coexistence of small cell neuroendocrine carcinoma and villous adenoma in the ampulla of Vater

Small cell neuroendocrine carcinoma of the ampulla of Vater is extremely rare and different from the common ampullary adenocarcinoma. The ampullary adenoma is also a rare neoplasm and has the potential to develop an adenocarcinoma. Their coexistence has been rarely reported in the literature. We herein describe an unusual case of a small cell neuroendocrine carcinoma associated with a villous adenoma in the ampulla of Vater with emphasis on computed tomography (CT) and histopathological findings. We also discuss their clinical, histopathological and radiological features as well as possible histogenesis.

Pyogenic liver abscess associated with large colonic tubulovillous adenoma

Pyogenic liver abscesses usually occur in association with a variety of diseases. Rarely, liver abscess has been reported as the presenting manifestation of colonic tubulovillous adenoma. We report two cases of pyogenic liver abscess without hepatobiliary disease or other obvious etiologies except that one had a history of diabetes mellitus （DM）. The pathogen in the patient with DM was Klebsiella pneumonia （KP）. In both of the patients, Ueus developed about two to three weeks after the diagnosis of liver abscess. Colonoscopy revealed large polypoid tumors with pathological findings of tubulovillous adenoma in both cases. Two lessons were learned from these two cases： （1） an underlying cause should be aggressively investigated in patients with cryptogenic liver abscess; （2） DM could be one of the etiologies but not necessarily the only cause of KP liver abscess.

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.

Pediatric intrahepatic bile duct adenoma-rare liver tumor: A case report

BACKGROUND Intrahepatic bile duct adenoma(BDA)is one of the rarest of the rare benign tumors of the liver in the pediatric age group.It arises from the epithelial lining of intrahepatic bile ducts.The overall incidence of BDA is 1.3%of all primary benign liver tumors.Few case reports of this rare tumor occurring in adult population are present in the literature and to date,only one pediatric case has been reported worldwide.CASE SUMMARY An 18-month-old male child presented with chief complaints of mass per abdomen for 8 mo.Computerized tomography abdomen revealed a well-defined exophytic solid tumor arising from the posteroinferior margin of the right lobe of the liver with heterogenous enhancement and cystic changes,suggesting a suspicion of hepatoblastoma.Non-anatomical liver resection was done and a tumor of 10 cm×9.5 cm was excised.Histopathology of the specimen was conclusive with the diagnosis of intrahepatic bile duct adenoma,which was further supported by immunohistochemistry panel testing.The post-operative period was uneventful.On follow-up,the child was doing well and had no postoperative complication.CONCLUSION Intrahepatic bile duct adenoma in children is very rare and to date only one case has been reported.This is the second pediatric case of intrahepatic bile duct adenoma in the world.Additionally this is the first ever case of such a large tumor presenting in a child.

Hepatitis C virus core proteins derived from different quasispecies of genotype 1b inhibit the growth of Chang liver cells

AIM: To investigate the influence of different quasispecies of hepatitis C virus (HCV) genotype 1b core protein on growth of Chang liver cells. METHODS: Three eukaryotic expression plasmids (pEGFP-N1/core) that contained different quasispecies truncated core proteins of HCV genotype 1b were constructed. These were derived from tumor (T) and non- tumor (NT) tissues of a patient infected with HCV and C191 (HCV-J6). The core protein expression plasmids were transiently transfected into Chang liver cells. At different times, the cell cycle and apoptosis was assayed by flow cytometry, and cell proliferation was assayed by methyl thiazolyl tetrazolium (MTT) assay. RESULTS: The proportion of S-phase Chang liver cells transfected with pEGFP-N1/core was significantly lower than that of cells transfected with blank plasmid at three different times after transfection (all P < 0.05). The proliferation ratio of cells transfected with pEGFP-N1/corewas significantly lower than that of cells transfected with blank plasmid. Among three different quasispecies, T, NT and C191 core expression cells, there was no significant difference in the proportion of S- and G0/G1-phase cells. The percentage of apoptotic cells was highest for T (T > NT > C191), and apoptosis was increased in cells transfected with pEGFP-N1/core as the transfection time increased (72 h > 48 h > 24 h). CONCLUSION: These results suggest that HCV genotype 1b core protein induces apoptosis, and inhibits cell- cycle progression and proliferation of Chang liver cells. Different quasispecies core proteins of HCV genotype 1b might have some differences in the pathogenesis of HCV persistent infection and hepatocellular carcinoma.

Metabolism of Mequindox in Isolated Rat Liver Cells

Mequindox （MEQ）, 3-methyl-2-quinoxalinacetyl-l,4-dioxide, is widely used in Chinese veterinary medicine as an antimicrobial agent and feed additive. Its toxicity has been reported to be closely related to its metabolism. To understand the pathways underlying MEQ＇s metabolism more clearly, we studied its metabolism in isolated rat liver cells by using liquid chromatography coupled with electrospray ionization hybrid linear trap quadrupole orbitrap （LC-LTQ-Orbitrap） mass spectrometry. The structures of MEQ metabolites and their product ions were readily and reliably characterized on the basis of accurate MS2 spectra and known structure of MEQ. Eleven metabolites were detected in isolated rat liver cells, two of which were detected for the first time in vitro. The major metabolic pathways reported previously for in vitro metabolism of MEQ in rat microsomes were confirmed in this study, including N O group reduction, carbonyl reduction, and methyl monohydroxylation. In addition, we fotmd that acetyl hydroxylation was an important pathway of MEQ metabolism. The results also demonstrate that cellular systems more closely simulate in vivo conditions than do other in vitro systems such as microsomes. Taken together, these data contribute to our understanding of the in vivo metabolism of MEQ.

Pleomorphic Adenoma with Exuberant Squamous Metaplasia and Keratin Cysts Mimicking Squamous Cell Carcinoma in Minor Salivary Gland

Salivary gland tumors, the second most common neoplasm of the mouth after squamous cell carcinoma, account for a significant proportion of tumors of the oral and perioral regions. An unusual case of adenoma presented as a solitary intraoral palatine mass in a 32-year-old woman is reported here. The tumor was interpreted as an unusual pleomorphic adenoma because of the presence of exuberant squamous metaplasia, clinically mimicking squamous cell carcinoma. Moreover, the presence of cystic structures filled with keratinized material was also salient feature. Pleomorphic adenomas may occasionally display focal squamous metaplastic changes;when extensive, it presents the potential for misinterpretation of the histology as indicative of well-differentiated squamous cell carcinoma.

Liver transplantation for recurrent hepatic adenoma

Hepatic adenoma (HA) is a rare indication for liver transplantation (LTx). So far 20 cases of LTx for HA are reported in PubMed. In rare cases HA presents as multiple hepatic adenomas or recurrent adenoma after initial liver resection and in such cases LTx is the only potential cure and prevents the risk of bleeding or cancer transformation into hepatocellular carcinoma. We report the case of a 56 years old lady who underwent a left hepatectomy for giant adenoma in 2005 and resection of segment Ⅴ-Ⅵ for recurrence of liver adenoma in 2007. She developed a second recurrence of HA with 3 new lesions in the right liver in 2008. The patient underwent LTx. After 3 years the patient is alive with no evidence of disease. LTx is indicated in patients with HA in which resection is not technically feasible.

Malignant transformation of hepatocellular adenoma in a young female patient after ovulation induction fertility treatment:A case report

BACKGROUND Hepatocellular adenoma(HCA) is a rare benign liver tumor usually affecting young women with a history of prolonged use of hormonal contraception.Although the majority is asymptomatic, a low proportion may have significant complications such as bleeding or malignancy. Despite responding to the hormonal stimulus, the desire for pregnancy in patients with small HCA is not contraindicated. However, through this work we demonstrate that intensive hormonal therapies such as those used in the treatment of infertility can trigger serious complications CASE SUMMARY A 33-year-old female with a 10-year history of oral contraceptive use was diagnosed with a hepatic tumor as an incidental finding in an abdominal ultrasound. The patient showed no symptoms and physical examination was unremarkable. Laboratory functional tests were within normal limits and tests for serum tumor markers were negative. An abdominal magnetic resonance imaging(MRI) was performed, showing a 30 mm × 29 mm focal lesion in segment VI of the liver compatible with HCA or Focal Nodular Hyperplasia with atypical behavior. After a total of six years of follow-up, the patient underwent ovulation induction treatment for infertility. On a following MRI, a suspected malignancy was warned and hence, surgery was decided. The surgical specimen revealed malignant transformation of HCA towards trabecular hepatocarcinoma with dedifferentiated areas. There was non-evidence of tumor recurrence after three years of clinical and imaging follow-up.,CONCLUSION HCAs can be malignant regardless its size and low-risk appearance on MRI when an ovultation induction therapy is indicated.

PANETH CELL ADENOMA OF THE STOMACH

Two cases of Paneth cell adenoma of the stomach are reported and the histological, ultrastructural, immunohistochemical and immunocytochemical features are described. The surgical specimens showed varied pictures of dysplasia with severe atrophic gastritis and Intestinal metaplasia. 60%-70% of the tumor cells contained coarse cytoplasmic granules stained red with eosin or PAS but remained unstained with aician blue pH2. 5 and exhibited positive immunostaining for lysozyme. The nature of these granules was confirmed by electron microscopy and immunoelectron microscopy. In addition, some enldocrine cells were detected in the neoplastic glands. The characteristics of Paneth cell adenoma of the stomach are discussed. There might be a close relation in the histogenesis with intestinal metaplasia suggested.