Primary combined hepatocellular-cholangiocellular sarcoma:An unusual case

Primary liver carcinosarcoma is rare. Here we report an unusual case of liver carcinosarcoma containing combined hepatocellular cholangiocarcinoma. A mass in the right liver lobe of a 45-year-old man was accidentally discovered by ultrasonic inspection and computed tomography(CT) scan. Surgical resection was performed following a diagnosis of primary liver cancer. Micropathologically, both carcinomatous and sarcomatous elements were present, and diagnosis of liver carcinosarcoma was confirmed. The carcinomatous element consisted of hepatocellular carcinoma and foci of cholangiocellular carcinoma. The sarcomatous element was composed of spindle cells and bizarre cells,as well as foci of osteosarcoma and chondrosarcoma.Hepatocellular carcinoma cells diffusely expressed both hepatocyte specific markers cytokeratin(CK)8/18 and cholangiocyte specific markers CK19, and sarcoma cells were positive for vimentin. Interestingly,both carcinomatous and sarcomatous cells expressed epithelial membrane antigen. CD117-positive ductular reactions and small undifferentiated cells were observed.A liver progenitor cell origin of the liver carcinosarcoma was proposed.

Multi-disciplinary treatment for cholangiocellular carcinoma

Cholangiocarcinoma(CC)is rare malignant tumors composed of cells that resemble those of the biliary tract.It is notoriously difficult to diagnose,and is associated with a high mortality.Traditionally,CC is divided into intrahepatic and extraheaptic disease according to its location within the biliary tree.Intrahepatic cholangiocellular carcinoma(IH-CCC)or peripheral cholangiocellular carcinoma(CCC)appears within the second bifurcation of hepatic bile duct,and is the second most common primary liver cancer following hepatocellular carcinoma(HCC),IH-CCC or peripheral CCC often presents with advanced clinical features,and the cause for this cancer rise is still unclear.MRI,CT and PET provide useful diagnostic information in those patients.Surgical resection is the only chance for cure,with results depending on selected patients and careful surgical technique.Liver transplantation could offer long-term survival in selected patients when combined with chemotherapy.Chemotherapy,radiation therapy or combination therapies remain as the only treatment for inoperable patients.However,these are uniformly ineffective in patients' survival.

Combined hepatocellular and cholangiocellular carcinoma presenting with radiological characteristics of focal nodular hyperplasia

Combined hepatocellular and cholangiocellular carcinoma (cHCC-CC) is a rare tumor type containing unequivocal elements of both hepatocellular carcinoma and cholangiocarcinoma that are intimately mixed. Although these tumors are usually considered to be more related to hepatocellular carcinoma than to cholangiocarcinoma, they sometimes, in contrast to hepatocellular carcinoma, contain a significant amount of fibrous stroma. This might in some cases explain atypical radiological features. We report a case of a cHCC-CC in a 47-year-old female that resembled focal nodular hyperplasia on Magnetic Resonance Imaging. Correlation of imaging and serum levels of α-fetoprotein and CA19.9 can help to make the correct diagnosis preoperatively.

Initial experience from a combination of systemic and regional chemotherapy in the treatment of patients with nonresectable cholangiocellular carcinoma in the liver

AIM: In nonresectable cholangiocellular carcinoma (CCC)therapeutic options are limited. Recently, systemic chemotherapy has shown response rates of up to 30%.Additional regional therapy of the arterially hyper vascularized hepatic tumors might represent a rational approach in an attempt to further improve response and palliation. Hence, a protocol combining transarterial chemoembolization and systemic chemotherapy was applied in patients with CCC limited to the liver.METHODS: Eight patients (6 women, 2 men, mean age 62 years) with nonresectable CCC received systemic chemotherapy (gemcitabine 1 000 mg/m2) and additional transarterial chemoembolization procedures (50 mg/m2cisplatin, 50 mg/m2 doxorubicin, up to 600 mg degradable starch microspheres). Clinical follow-up of patients, tumor markers, CT and ultrasound were performed to evaluate maximum response and toxicity.RESULTS: Both systemic and regional therapies were tolerated well; no severe toxicity (WHO Ⅲ/Ⅳ) was encountered. Nausea and fever were the most commonly observed side effects. A progressive rarefication of the intrahepatic arteries limited the maximum number of chemoembolization procedures in 4 patients. A median of 2 chemoembolization cycles (range, 1-3) and a median of 6.5 gemcitabine cycles (range, 4-11) were administered.Complete responses were not achieved. As maximum response, partial responses were achieved in 3 cases,stable diseases in 5 cases. Two patients died from progressive disease after 9 and 10 mo. Six patients are still alive. The current median survival is 12 mo (range, 9-18); the median time to tumor progression is 7 mo (range, 3-18). Seven patients suffered from tumor-related symptoms prior to therapy, 3 of these experienced a treatment-related clinical relief. In one patient the tumor became resectable under therapy and was successfully removed after 10 mo.CONCLUSION: The present results indicate that a combination of systemic gemcitabine therapy and repeated regional chemoembolizations is well tolerated and may enhance the effect of palliation in a selected group of patients with intrahepatic nonresectable CCC.

Primary biliary cholangitis metachronously complicated with combined hepatocellular carcinoma-cholangiocellular carcinoma and hepatocellular carcinoma

Primary biliary cholangitis(PBC) is a progressive cholestatic liver disease characterized by the presence of highly specific antimitochondrial antibodies, portal inflammation and lymphocyte-dominated destruction of the intrahepatic bile ducts, which leads to cirrhosis. While its pathogenesis remains unclear, PBC that shows histological progression to fibrosis carries a high risk of carcinogenesis; the same is true of viral liver diseases. In patients with PBC, the development of hepatocellular carcinoma(HCC) is rare; the development of combined hepatocellular carcinoma and cholangiocellular carcinoma(c HCC-CCC) is extraordinary. Herein, we report a rare case of PBC metachronously complicated by c HCC-CCC and HCC, which, to the best of our knowledge, has never been reported. We present a case report of a 74-year-old Japanese woman who was diagnosed as PBC in her 40's by using blood tests and was admitted to our department for further management of an asymptomatic liver mass. She had a tumor of 15 mm in size in segment 8 of the liver and underwent a partial resection of the liver. Subsequent pathological findings resulted in the diagnosis of c HCC-CCC, arising from stage 3 PBC. One year after the initial hepatectomy, a second tumor of 10 mm in diameter was found in segment 5 of the liver; a partial resection of the liver was performed. Subsequent pathological findings led to HCC diagnosis. The component of HCC in the initial tumor displayed a trabecular growth pattern while the second HCC showed a pseudoglandular growth pattern, suggesting that metachronous tumors that arise from PBC are multicentric.

Three-in-one incidence of hepatocellular carcinoma,cholangiocellular carcinoma,and neuroendocrine carcinoma:A case report

BACKGROUND Primary hepatic neuroendocrine carcinoma(NEC)is rare,and a combination with hepatocellular carcinoma(HCC)and cholangiocarcinoma(CCA)is extremely rare.To date,only four combination cases have been reported.The present paper describes the fifth patient.CASE SUMMARY A 32-year-old Chinese man with chronic hepatitis B was hospitalized for persistent upper abdominal pain.Abdominal computed tomography(CT)examination revealed a liver mass.The tumor was located in the 7th and 8th segments of the liver,and CT and magnetic resonance imaging findings were consistent with the diagnosis of HCC.Laboratory examinations revealed the following:Alanine aminotransferase,243 U/L;aspartate aminotransferase,167 U/L;alpha-fetoprotein,4519μg/L.Laparoscopic right lobe hepatectomy was performed on the liver mass.Postoperative pathology showed low differentiation HCC plus medium and low differentiation CCA combined with NEC.One month after the surgery,the patient suffered from epigastric pain again.Liver metastasis was detected by CT,and tumor transcatheter arterial chemoembolization was performed.Unfortunately,the liver tumor was progressively increased and enlarged,and after 1 mo,the patient died of liver failure.CONCLUSION This is a rare case,wherein the tumor is highly aggressive,grows rapidly,and metastasizes in a short period.Imaging and laboratory tests can easily misdiagnose or miss such cases;thus,the final diagnosis relies on pathology.

THE EXPRESSION OF CYTOKERATINS IN HUMAN HEPATOCELLULAR AND CHOLANGIOCELLULAR CARCINOMAS

In order to determine the usefulness value of the antibodies to cytokeratins(CK) of'bile duct type'in the differential diagnosis between hepatocellular carcinoma(HCC) and cholangiocellular carcinoma(CC),we have made an immunocytochemical investigation,using the antibodies specifically recognizing CK19 and CK18,seperately,in liver,and laminin(LN) antibody.All the CC examined(10 cases) were found CK19-positive;interestingly,CK19-positive cancer cells were also observed in 38% of HCCs(14/37).Therefore,CK19 was not a reliable marker in differentiating HCC from CC,in our consideration.The CK19 expression in HCC was showed to be irrelevant to their differentiation degres,but related to the histologic subtypes which indicated the directions of their differentiation.CK19 expression was observed in all the HCC cell nests with glandular differentiation,and an untontinuous LN-Positive basement membrane-like structure was immunolocalized around these cells.Which indicated that the glandular differentiation and CK19 expression in HCC were also related to the LN deposition,as in fetal liver and some chronic liver disorders.

New approaches to diagnostics and treatment of cholangiocellular cancer based on photonics methods

Cholangiocellular cancer(CCC)is an oncological disease of the bile ducts characterized by a high mortality rate.To date,the use of standard methods for the diagnosis and treatment of CCC has not been able to reduce mortality from this disease.This work presents the results of fluorescence diagnostics(FD),which consists in using a modified optical fiber and photodynamic therapy(PDT)using a therapeutic laser instead of a low-intensity laser.This technique was tested on 43 patients in a clinical setting.The results obtained indicate a direct correlation between spectroscopic and video FD methods.Furthermore,a direct correlation was found between the photobleaching of a chlorin e6-based photosensitizer,with the commercial names of PhotoIon Radachlorin and Photoran and stricture regression.Our findings demonstrate the possibility of using a therapeutic laser with a wavelength of 660 nm for both diagnosis and treatment of bile ducts cancer,which results in a significant reduction of the operation time without decreasing its effectiveness.

晚期dMMR/MSI-H肝内胆管细胞癌1例报告

胆道恶性肿瘤(biliary tract cancer,BTC)占所有消化系肿瘤的3%[1],在原发性肝胆恶性肿瘤发病率中占据第二位[2],肝内胆管癌(intrahepatic cholangiocarcinoma,ICCA)属于BTC的一种,我国BTC中仅有1.3%至10.0%患者表现为MSI-H,32.3%至42.86%患者表现为PD-L1阳性[3],因此MSI-H、PD-L1阳性的ICCA患者极具讨论价值。

基于生物信息学构建肝内胆管癌生存预测模型及验证

目的通过生物信息学的方法挖掘肝内胆管癌(ICC)潜在的预后标志物,构建生存预测模型以更好地指导临床治疗。方法通过TCGA-CHOL和GSE107943数据集来寻找差异基因,基于加权相关网络分析(WGCNA)算法,构建无尺度网络寻找和肿瘤发生联系紧密的基因模块。将差异基因与模块内的基因取交集,通过单因素COX和Lasso-cox回归模型构建ICC的预后风险模型,E-MTAB-6389数据集用于外部验证,对于参与模型构建的关键基因,在13个ICC配对肿瘤样本中验证蛋白表达情况。另外收集我院2017年6月—2021年6月80例手术后的ICC患者临床病理资料,电话随访的方式获得患者生存数据。根据免疫组化半定量的方法,对独立预后危险基因的蛋白表达情况进行打分,用二分类的方式将患者分为高、低表达组,比较不同分组患者总生存期(OS)的差异,并分析独立预后危险基因与临床病理特征之间的关系。结果将差异基因与WGCNA中蓝色基因模块中的基因取交集得到958个基因。通过单因素Cox和Lasso-Cox回归分析得到用于模型构建的5个关键基因(CFH、EGR4、RERG、PRICKLE1、NIPA1)。高风险患者OS明显低于低风险的患者。对模型效能进行评估,1、3、5年ROC曲线下的面积分别为0.858、0.881、0.975。校准曲线对列线图进行评价,提示列线图准确性较高,并通过外部队列E-MTAB-6389进行验证,同样说明模型准确性良好。CFH蛋白表达与远处转移、淋巴结转移,以及TNM分期相关,可以作为ICC独立预后危险基因。结论本研究构建的CFH、EGR4、RERG、PRICKLE1、NIPA15基因风险预后模型具有较好的预测效能,能够对ICC患者的预后评估提供参考。

肝内胆管细胞癌增强CT扫描特征及其诊断价值分析

目的分析肝内胆管细胞癌(ICC)的CT增强扫描特征,探讨其诊断价值。方法2020年3月~2023年3月我院诊治的376例经超声检查发现的肝脏占位性病变患者,均行CT平扫和多期增强扫描检查,所有患者接受穿刺活检或手术组织病理学检查诊断。采用kappa系数检验CT扫描的诊断价值。结果在376例肝占位性病变患者中,经病理学检查诊断为良性病变149例和恶性病变227例,后者包括ICC者18例和肝细胞癌(HCC)者209例;CT增强扫描检出良性病变151例,恶性病变225例;CT扫描诊断ICC患者21例,均为单发病灶,肝左叶病灶占61.9%,病灶直径为(6.7±1.8)cm,肿块型病灶占57.1%。肿块型动脉期主要为病灶边缘薄层轻度强化,静脉期均显示病灶边缘薄层轻度强化,延迟期均显示病灶强化加强;腔内生长型动脉期主要为肝门附近局部软组织病灶轻度强化,静脉期均显示病灶进一步强化,延迟期均显示病灶缓慢持续强化;浸润型动脉期主要为肝内胆管壁轻度强化,静脉期均显示病灶进一步强化,延迟期均显示病灶缓慢持续强化;在CT增强扫描检出的225例恶性病变患者中,经病理学检查诊断为非ICC者208例,ICC者17例;多期CT增强扫描检出非ICC者204例,ICC者21例,其诊断ICC与病理组织学检查一致性检验的Kappa值为0.766,其准确率、敏感度、特异度、阳性预测值和阴性预测值分别为94.1%、97.6%、97.3%、76.2%和99.5%。结论多期CT增强扫描诊断ICC的准确度较高,其扫描特征对指导临床手术方案的选择具有重要的意义。

Clinical features,histology,and histogenesis of combined hepatocellular-cholangiocarcinoma

Combined hepatocellular-cholangiocarcinoma(CHC) is a rare tumor with poor prognosis,with incidence ranging from 1.0%-4.7% of all primary hepatic tumors.This entity will be soon renamed as hepato-cholangiocarcinoma.The known risk factors for hepatocellular carcinoma(HCC) have been implicated for CHC including viral hepatitis and cirrhosis.It is difficult to diagnose this tumor pre-operatively.The predominant histologic component within the tumor largely determines the predominant radiographic features making it a difficult distinction.Heterogeneous and overlapping imaging features of HCC and cholangiocarcinoma should raise the suspicion for CHC and multiple core biopsies(from different areas of tumor) are recommended before administering treatment.Serum tumor markers CA19-9 and alpha-fetoprotein can aid in the diagnosis,but it remains a challenging diagnosis prior to resection.There is sufficient data to support bipotent hepatic progenitor cells as the cell of origin for CHC.The current World Health Organization classification categorizes two main types of CHC based on histo-morphological features:Classical type and CHC with stem cell features.Liver transplant is one of the available treatment modalities with other management options including transarterial chemoembolization,radiofrequency ablation,and percutaneous ethanol injection.We present a review paper on CHC highlighting the risk factors,origin,histological classification and therapeutic modalities.

周围型胆管细胞性肝癌影像学诊断

胆管细胞性肝癌是肝脏常见的原发性恶性肿瘤之一 ,根据部位分为周围型和肝门型两类。本文综述了周围型胆管细胞性肝癌的临床表现、病因、病理学改变以及与之相关的影像学表现特征 。

41例肝内胆管细胞癌的临床特点及其预后观察

目的:评价肝内胆管细胞癌的临床特点和治疗方法及预后相关因素以指导临床诊治,提高生存率。方法:分析中国医学科学院肿瘤医院1970年1月～2005年1月收治的41例肝内胆管细胞癌患者的临床资料,所有患者均获随访。结果:41例患者中AFP阳性率9.8%(4/41),肝硬化阳性率22.0%(9/41)。根治性切除组1、3、5年生存率82.3%、45.8%、45.8%;非根治性切除组1、3年生存率9.2%、0%。Cox比例风险模型多因素分析根治性切除(P<0.01)、淋巴结转移(P<0.01)、术前直接胆红素水平(P=0.012)是影响预后的独立因素。结论:肝内胆管细胞癌以手术治疗为主。根治性手术切除是获得长期生存的唯一途径。根治性切除、淋巴结转移、术前胆红素水平是影响预后的独立因素。

不同肝癌分期系统预测混合型肝细胞-胆管细胞癌患者手术预后的比较

目的比较不同原发性肝癌分期系统对混合型肝细胞-胆管细胞癌(c HCC-CC)手术治疗患者的预后预测能力。方法将2005年5月至2013年8月在中国人民解放军总医院行手术治疗、有术后病理确诊结果、临床资料和随访资料完备的54例c HCC-CC纳入研究。利用8种肝癌分期系统对该组病例分期,采用病例构成比、生存曲线、受试者工作特征曲线分别比较各分期系统的病例分层能力、预后区分能力及预后结果预测能力。结果肝内胆管癌肿瘤-淋巴结-转移[TNM(ICC)]分期及日本集成分期评分病例构成相对均衡。本组病例术后12和24个月累计生存率分别为65.5%、56.3%。各期生存曲线差异有统计学意义(P<0.05)的分期有TNM(ICC)分期(Ⅰ期比Ⅱ期,P=0.012;Ⅱ期比Ⅲ&Ⅳ期,P=0.002)、奥田邦雄分期(Ⅰ期比Ⅱ期,P=0.025)、法国分期(A期比B期,P=0.045)。术后12和24个月各分期系统受试者工作特征曲线下面积由大到小分别为TNM(ICC)分期(0.836、0.847)、巴塞罗那临床肝癌分期(0.744、0.780)、日本集成分期评分(0.723、0.764)、意大利肝癌评分(0.710、0.786),其余分期系统的受试者工作特征曲线下面积差异无统计学意义。结论 TNM(ICC)分期对c HCC-CC病例分层能力、预后区分能力及预后结果预测能力均优于其他7种分期系统。

Characterization of focal liver masses using acoustic radiation force impulse elastography

AIM:To investigate the diagnostic performance of acoustic radiation force impulse(ARFI) elastography for characterizing focal liver mass by quantifying their stiffness.METHODS:This prospective study included 62 patients with a focal liver mass that was well visualized on conventional ultrasonography performed in our institution from February 2011 to November 2011.Among them,12 patients were excluded for ARFI measurement failure due to a lesion that was smaller than the region of the interest and at an inaccessible location(deeper than 8 cm)(n = 7) or poor compliance to hold their breath as required(n = 5).Finally,50 patients with valid ARFI measurements were enrolled.If a patient had multiple liver masses,only one mass of interest was chosen.The masses were diagnosed by histological examination or clinical diagnostic criteria.During ultrasonographic evaluation,stiffness,expressed as velocity,was checked 10 times per focal liver mass and the surrounding liver parenchyma.RESULTS:After further excluding three masses that were non-diagnostic on biopsy,a total of 47 focal mass lesions were tested,including 39(83.0%) malignant masses [24 hepatocellular carcinomas(HCC),seven cholangiocellular carcinomas(CCC),and eight liver metastases] and eight(17.0%) benign masses(five hemangiomas and three focal nodular hyperplasias,FNH).Thirty-seven(74.0%) masses were confirmed by histological examination.The mean velocity was 2.48 m/s in HCCs,1.65 m/s in CCCs,2.35 m/s in metastases,1.83 m/s in hemangiomas,and 0.97 m/s in FNHs.Although considerable overlap was still noted between malignant and benign masses,significant differences in ARFI values were observed between malignant and benign masses(mean 2.31 m/s vs 1.51 m/s,P = 0.047),as well as between HCCs and benign masses(mean 2.48 m/s vs 1.51 m/s,P = 0.006).The areas under the receiver operating characteristics curves(AUROC) for discriminating the malignant masses from benign masses was 0.724(95%CI,0.566-0.883,P = 0.048),and the AUROC for discriminating HCCs from benign masses was 0.813(95%CI,0.649-0.976,P = 0.008).To maximize the sum of sensitivity and specificity,an ARFI value of 1.82 m/s was selected as the cutoff value to differentiate malignant from benign liver masses.Furthermore,the cutoff value for distinguishing HCCs from benign masses was also determined to be 1.82 m/s.The diagnostic performance of the sum of the ARFI values for focal liver masses and the surrounding liver parenchyma to differentiate liver masses improved(AUROC = 0.853;95%CI,0.745-0.960;P = 0.002 in malignant liver masses vs benign ones and AUROC = 0.948;95%CI,0.896-0.992,P < 0.001 in HCCs vs benign masses).CONCLUSION:ARFI elastography provides additional information for the differential diagnosis of liver masses.However,our results should be interpreted in clinical context,because considerable overlap in ARFI values existed among liver masses.

Liver surgery in cirrhosis and portal hypertension

The prevalence of hepatic cirrhosis in Europe and the United States, currently 250 patients per 100000 inhabitants, is steadily increasing. Thus, we observe a significant increase in patients with cirrhosis and portal hypertension needing liver resections for primary ormetastatic lesions. However, extended liver resections in patients with underlying hepatic cirrhosis and portal hypertension still represent a medical challenge in regard to perioperative morbidity, surgical management and postoperative outcome. The Barcelona Clinic Liver Cancer classification recommends to restrict curative liver resections for hepatocellular carcinoma in cirrhotic patients to early tumor stages in patients with Child A cirrhosis not showing portal hypertension. However, during the last two decades, relevant improvements in preoperative diagnostic, perioperative hepatologic and intensive care management as well as in surgical techniques during hepatic resections have rendered even extended liver resections in higher-degree cirrhotic patients with portal hypertension possible. However, there are few standard indications for hepatic resections in cirrhotic patients and risk stratifications have to be performed in an interdisciplinary setting for each individual patient. We here review the indications, the preoperative risk-stratifications, the morbidity and the mortality of extended resections for primary and metastatic lesions in cirrhotic livers. Furthermore, we provide a review of literature on perioperative management in cirrhotic patients needing extrahepatic abdominal surgery and an overview of surgical options in the treatment of hepatic cirrhosis.

肝内胆管细胞癌的影像学诊断

目的探讨肝内胆管细胞癌(ICC)的CT及MRI表现及病理基础。方法回顾性分析经手术及病理证实的肝内胆管细胞癌24例。所有病例均行B超检查,17例行CT平扫和增强扫描,14例行MRI平扫和增强扫描。结果 CT平扫病灶均为低密度,边界不清,MRI表现为T1WI低信号,T2WI呈较高信号伴中心低信号,动态CT及MRI检查病灶多表现为渐进性的向心性强化,病灶局部肝包膜可有回缩,周围肝内胆管可有轻度扩张和结石;病理表现镜下为低分化或未分化腺癌,血管分布稀少,癌巢之间为大量纤维结缔组织。CT早期强化17.6%(3/17),延迟强化82.3%(14/17),MRI检查14例T1WI低信号T2WI略高信号,边界不清,形态不规则,远端胆管迂曲扩张。MRI增强通常表现为早期轻度或中度不全边缘强化,晚期进行性同心性强化,在延迟期中心区通常为不完全强化。结论肝内胆管细胞癌CT多期增强扫描及MR动态增强扫描均具有一定的特异性,对于肝内与其它常见病变的鉴别诊断均有重要价值.

周围型肝内胆管细胞癌的磁共振诊断

目的 :评价磁共振 (MRI)平扫及联合动态增强MRI对周围型肝内胆管细胞癌 (PCC)的诊断价值。方法 :回顾性分析 15例经手术病理证实的周围型肝内胆管细胞癌的MRI平扫及动态增强表现。结果 :全部病灶显示满意。参考平扫胆管扩张情况定性诊断符合率为 3 3 .3 % ,联合动态增强定性符合率提高至 86.7%。结论 :MRI平扫能较好显示病灶和胆管扩张情况 ,平扫联合动态增强检查可提高对PCC的定性符合率。

Combined hepatocellular and cholangiocarcinoma originating from the same clone:a pathomolecular evidence-based study

Background:Combined hepatocellular and cholangiocarcinoma(CHC) is a unique subtype of liver cancer comprising both hepatocellular carcinoma(HCC) and intrahepatic cholangiocarcinoma(ICC);however,its cellular origin remains unclear.The purpose of this study was to investigate the clinicopathologic features and the clonal relationship between HCC and ICC in 34 patients with CHC.Methods:The clinicopathologic features and prognosis of the 34 CHC patients were compared with those of 29 patients with separated HCC and ICC(5HC).Loss of heterozygosity(LOH) at 10 highly polymorphic microsatellite markers was detected in 16 CHC and 10 SHC tissues for determination of the clonal origin of CHC.Expression of hepatocyte markers[hepatocyte paraffin 1(Hep Par 1) and glypican 3(GPC3)]and cholangiocyte markers[cytokeratin(CK)7 and 19]in tumor tissues was examined by immuno histochemical analysis.Results:In the 16 CHC specimens,the difference in LOH patterns between HCC and ICC was less than 30%,suggesting the same clonal origin of HCC and ICC.Consistent with this finding,immunohistochemical analysis revealed that hepatocyte markers(Hep Par 1 and GPC3) and cholangiocyte markers(CK7 and CK19) were simultaneously expressed in both the HCC and ICC components in 52.9%of CHC specimens,suggesting that the two components shared a similar phenotype with hepatic progenitor cells(HPCs).On the contrary,in all 10 SHC cases,the difference in LOH patterns between the HCC and ICC components was greater than 30%,suggesting different clonal origins of HCC and ICC.Overall survival and disease-free survival were shorter for patients with CHC than for patients with SHC(P < 0.05).Conclusions:Our results suggest that the HCC and ICC components of CHC may originate from the same clone,having the potential for dual-directional differentiation similar to HPCs.CHC tended to exhibit the biological behaviors of both HCC and ICC,which may enhance the infiltrative capacity of tumor cells,leading to poor clinical outcomes for patients with CHC.