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.

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.

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.

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。

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.

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。

Extrahepatic intraductal ectopic hepatocellular carcinoma:bile duct filling defect

BACKGROUND:Obstructive jaundice caused by an intraductal hepatocellular carcinoma is a rare initial symptom.We report a rare case of an extrahepatic icteric type hepatocellular carcinoma.METHODS:A 75-year-old patient was admitted to our hospital because of obstructive jaundice 3 months after resection of multilocular hepatocellular carcinoma.A postoperative bile leakage was treated by placement of a decompressing stent in the common bile duct.Endoscopic retrograde choledochoscopy showed extended blood clots filling the bile duct system and computed tomography revealed a local swelling in the common extrahepatic bile duct.The level of alpha-fetoprotein(AFP)was only slightly elevated but that of CA19-9 was dramatically increased.Cholangiography showed an intraductal filling defect typical of a cholangiocellular carcinoma.RESULTS:Bile duct brushing cytology showed no cholangiocellular carcinoma but hepatocellular carcinoma cells in the extrahepatic bile duct.An extrahepatic bile duct resection was performed.Histological examination confirmed the diagnosis of extrahepatic intraductal growth of hepatocellular carcinoma.CONCLUSION:Ectopic hepatocellular carcinoma is a rare but important differentially diagnosed of extrahepatic bile duct filling defect.

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.

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.

肝内胆管细胞癌术后复发转移机制与临床防治策略

肝内胆管细胞癌是一种源于肝内胆管上皮细胞的原发性腺癌,肿瘤无包膜,肿瘤早期沿胆管周围淋巴管、血管、神经周围间隙及疏松纤维结缔组织等发生多途径浸润转移,以淋巴结转移为特征.由于早期无特征性临床表现,缺乏早期诊断特异分子标志物,手术切除率低,术后肿瘤复发转移率高,放化疗、分子靶向药物和免疫治疗疗效低,预后差.通过分子病理学、基因功能、影像技术深入研究,阐明肝内胆管细胞癌发生、复发转移机制,提高早期诊断率和精准临床分期,针对肿瘤复发转移危险因素采用个体化的精准治疗方案和预防措施,是降低肝内胆管细胞癌术后肿瘤复发与转移率,改善患者预后的关键.

基于MRI预测肿块型肝内胆管细胞癌分化程度的研究价值

目的:探讨磁共振成像(MRI)定性、定量参数在肿块型肝内胆管细胞癌细胞分化程度的预测价值。方法:回顾性分析2016年3月-2022年3月81例经手术病理证实为肿块型肝内胆管细胞癌(MICC)患者临床、病理、MRI资料。将患者分为中分化组(29例)和低分化组(52例),采用t检验或χ^(2)检验比较两组在临床、MRI定性以及定量参数方面的差异,将单因素分析中具有统计学差异的变量纳入Logistic回归进行分析用来建立MRI模型。受试者操作特征(ROC)曲线被用于分析模型的诊断效能。结果:单因素分析显示两组间肝内转移灶、动态强化模式、肝胆期强化模式、扩散加权成像(DWI)、直径的差异有统计学意义(P值分别为0.032、<0.001、0.035、0.017、0.001)。动态强化模式、直径是预测MICC分化程度的独立预测因子,所得MRI模型ROC曲线下面积0.806,敏感度71.2%,特异度79.3%。结论:动态强化模式、直径是预测MICC分化程度的独立危险因素,MRI模型具有良好的诊断效能。

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。

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。

肝内周围型胆管细胞癌的MRI诊断

目的探讨MRI对肝内周围型胆管细胞癌(IHPCC)的诊断及鉴别诊断价值。方法回顾性分析经手术病理证实的IHPCC 28例,分别作MRI平扫和动态增强扫描。结果在MRI图像上,IHPCC主要表现为分叶状或不规则形、混杂密度或信号、无包膜的软组织肿块;动态增强扫描肿瘤呈"慢进慢出"表现,动脉期肿瘤以边缘轻～中度强化为主,延迟扫描出现从周边到中心的向心性、延迟强化;其他征象包括瘤内见扩张的胆管8例,病灶周围或远端胆管扩张20例,包膜回缩征象12例,局部肝萎缩8例,肝门后或腹膜后淋巴结转移10例,均无门静脉癌栓形成。结论 IHPCC的MRI表现具有一定的特征性,可为IHPCC的诊断及鉴别诊断提供重要的依据;MRI新技术的应用更能反映肿瘤的病理特征。