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Cholangiolocellular carcinoma is a minor primary cancerous tumor of the liver and its coexistence with intrahepatic cholangiocarcinoma in the liver is rare. We herein report a case of concurrent cholangiolocellular carcinoma and intrahepatic cholangiocarcinoma in the liver, in addition to a rectal G1 neuroendocrine tumor, a so-called carcinoid. The intrahepatic tumors showed a different uptake in the 18F-fluoro-2-deoxyglucose (FDG) positron-emission tomography (PET)/computed tomography (CT) findings. In addition to conventional dynamic contrast-enhanced CT, we concluded that FDG PET/CT could therefore be a helpful modality to identify the properties of both cholangiolocellular carcinoma and intrahepatic cholangiocarcinoma.

Background Cholangiolocellular carcinoma (CoCC) is a rare primary liver tumor that shows mass-forming growth in most cases. At present, no effective treatment for hepatic recurrence CoCC has been established. We present a case involving a patient with recurrent disease that showed an intraductal growth (IG type) pattern of recurrence. The patient was treated with repeat hepatectomy with bile duct reconstruction. Case presentation The patient was a 76-year-old man with a history of S8 subsegmentectomy for CoCC. At 8 months after surgery, tumor marker elevation was observed. Computed tomography revealed a tumor occupying the right hepatic duct (B5-8) to B4 and the junction of the cystic duct. Endoscopic retrograde cholangiopancreatography (ERCP) and a thrombus biopsy with peroral cholangioscopy (POCS) confirmed the recurrence of CoCC in the intrahepatic bile duct. Although extended right lobectomy with extrahepatic bile duct resection was the optimal curative procedure, it was thought that it would be difficult due to his poor liver function. However, a slow-glowing recurrent tumor blocked the posterior branch of the portal vein; thus, the right liver lobe gradually shrank, and the estimated remnant liver volume increased in response, allowing curative surgery to finally be performed. At 10 months after surgery, the patient is alive without recurrence. Conclusions We reported a case of IG-type recurrence in the bile duct, which is an unusual pattern of intrahepatic recurrence, after initial surgery for CoCC. A slow-growing recurrent tumor exerted similar effects to PVE, which allowed for curative surgery to be performed.

Regeneration of the liver has been an interesting and well-investigated topic for many decades. This etiology and time-dependent mechanism has proven to be extremely challenging to investigate, certainly in human diseases. A reason for this challenge is found in the numerous interactions of different cell components, of which some are even only temporarily present (e.g., inflammatory cells). To orchestrate regeneration of the epithelial cells, their interaction with the non-epithelial components is of utmost importance. Hepatocytes, cholangiocytes, liver progenitor cells, and peribiliary glands have proven to be compartments of regeneration. The ductular reaction is a common denominator in virtually all liver diseases; however, it is predominantly found in late-stage hepatic and biliary diseases. Ductular reaction is an intriguing example of interplay between epithelial and non-epithelial cells and encompasses bipotential liver progenitor cells which are able to compensate for the loss of the exhausted hepatocytes and cholangiocytes in biliary and hepatocytic liver diseases. In this manuscript, we focus on the etiology-specific damage that is observed in different human diseases and how the liver regulates the regenerative response in an acute and chronic setting. Furthermore, we describe the importance of morphological keynotes in different etiologies and how spatial information is of relevance for every basic and translational research of liver regeneration. ispartof: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES vol:20 issue:9 ispartof: location:Switzerland status: published

To elucidate the dynamic CT features of pure type of cholangiolocellular carcinoma (pure CoCC) in comparison with those of cholangiocellular carcinoma (CCC) and to analyze their bases by angiography-assisted CT with histopathologic correlation. Surgically confirmed 10 pure CoCCs, 10 CCCs and 7 mixed CoCC and CCCs from August 2001 to May 2012 were included in this study. Among them, dynamic CT features were compared. In 8 pure CoCCs, the correlative study between angiography-assisted CT and histopathological study was performed to clarify the basic mechanism of dynamic CT features. All pure CoCCs showed early and prolonged enhancement homogeneously or inhomogeneously and 8 of 10 pure CoCCs showed early peritumoral enhancement on dynamic CT. Time-attenuation curve provided by dynamic CT showed significant higher Hounsfield unit value of pure CoCC than those of CCC at each phases (p

Background Cholangiolocellular carcinoma (CoCC) is a rare liver tumor arising from the canals of Hering found between the cholangioles and interlobular bile ducts. Although morphologically CoCC mimics intrahepatic cholangiocarcinoma (ICC), CoCC exhibits a unique intermediate biologic behavior between hepatocellular carcinoma (HCC) and ICC. Curative resection is required for prolonged survival in patients with CoCC. However, effective therapy for postoperative hepatic recurrence has not yet been standardized. Case presentation A 40-year-old man had an asymptomatic liver mass found during a regular medical examination. Contrast-enhanced computed tomography revealed a well-enhanced mass, 15 cm in diameter, in the right liver. He underwent right hemihepatectomy at a local hospital under the preoperative diagnosis of hepatocellular carcinoma. Pathologic examination confirmed a moderately differentiated tubular adenocarcinoma, leading to a diagnosis of ordinary ICC. Twelve months after surgery, he was referred to our hospital due to three hepatic recurrences in the left medial segment. He underwent partial hepatectomy for the recurrence, followed by adjuvant chemotherapy using gemcitabine alone. After the second hepatectomy, hepatic recurrences developed an additional seven times. The numbers and sizes of the recurrent tumors were very limited at each recurrence, satisfying the standard criteria for percutaneous radiofrequency ablation (RFA) for the treatment of HCC. All lesions were treated by percutaneous RFA, although this was an exceptional approach for ICC. He is now alive without evidence of disease 9.2 years after the first hepatectomy. Because his clinical outcome was satisfactory and not compatible with the typical negative outcomes of ordinary ICC, we re-reviewed the histological findings of his tumor. The tumor was composed of small gland-forming cells proliferating in an anastomosing pattern; the cell membrane was strongly immunoreactive for epithelial membrane antigen. These findings were in accordance with the typical features of CoCC, revising his final diagnosis from ICC to CoCC. Conclusions This case report demonstrates a satisfactory outcome using repeated local treatments, such as hepatectomy and RFA, for hepatic recurrences of CoCC, suggesting that a localized treatment approach can be considered to be a therapeutic option. We should be careful in making a definitive diagnosis of ICC and ruling out CoCC because the diagnosis potentially dictates the treatment strategy for recurrences.

Cholangiolocellular carcinoma is a minor primary cancerous tumor of the liver and its coexistence with intrahepatic cholangiocarcinoma in the liver is rare. We herein report a case of concurrent cholangiolocellular carcinoma and intrahepatic cholangiocarcinoma in the liver, in addition to a rectal G1 neuroendocrine tumor, a so-called carcinoid. The intrahepatic tumors showed a different uptake in the 18F-fluoro-2-deoxyglucose (FDG) positron-emission tomography (PET)/computed tomography (CT) findings. In addition to conventional dynamic contrast-enhanced CT, we concluded that FDG PET/CT could therefore be a helpful modality to identify the properties of both cholangiolocellular carcinoma and intrahepatic cholangiocarcinoma.

A 35-year-old male patient who showed sustained virological response (SVR) following treatment for hepatitis C virus infection developed liver cancer. The lesion was identified by imaging studies, with atypical findings suggestive of hepatocellular carcinoma. Partial hepatectomy was performed and the histopathological diagnosis was cholangiolocellular carcinoma (CLC). Only a few cases of CLC have been described in young patients who achieved SVR. Hepatologists should recognize the potential development of CLC even in young patients who achieve SVR, and the need for a close follow-up by imaging studies. In addition, true characteristics and cell origin of CLC were discussed in this report.

Highlights • Cholangiolocellular carcinoma (CoCC) is a rare type of liver cancer. • We report a 79-year-old woman with CoCC detected following elevated C19-9 levels. • Uniquely, the hepatic artery was observed penetrating the >60 mm tumor on imaging. • Recurrence with multiple liver metastases occurred 6 months after surgery. • Tumor size and/or this unique growth pattern may be risk factors for recurrence., Introduction Cholangiolocellular carcinoma (CoCC) is thought to originate from hepatic stem cells. Its clinical characteristics, including radiological and prognostic factors, remain unclear. Presentation of case A 79-year-old woman with hypertension was admitted to our hospital after abnormal tumor marker levels were detected during an annual physical examination. Her laboratory data results were within normal range, and she was classified as Child-Pugh A. Enhanced computed tomography revealed a tumor located on the left side of the liver, with a maximum size of 60 mm. The tumor showed heterogeneously enhancing edges in the arterial phase, while prolonged tumor enhancement was detected in the delayed phase. Tumor penetration by the left hepatic artery was evident, whereas the left portal vein was invaded by the tumor. The preoperative diagnosis was cholangiocellular carcinoma. Left hepatectomy and cholecystectomy were performed with no postoperative complications; the final diagnosis was CoCC. Multiple liver metastases appeared 6 months after surgery; the patient is now receiving systematic chemotherapy. Discussion While portal vein penetration into CoCCs has been reported, the same is not true of the hepatic artery; therefore, this case illustrates a unique tumor growth pattern. Conclusion A unique growth pattern as well as a large primary tumor may contribute to earlier recurrence.

Cholangiolocellular carcinoma (CLC) is classified into the following two subtypes: (a) pure biliary subtype without hepatocellular carcinoma (HCC) component and (b) hepatobiliary subtype with HCC component. The possibles of cell origin of the former subtype are cholangiole, interlobular duct, and ordinary intrahepatic bile duct (septal or larger duct). The cell origin of the latter type may be HCC. The Japanese General Rules for the Clinical and Pathological Study of Primary Liver Cancer described the features of pure biliary type. Whereas World Health Organization Classification 2010 put an emphasis on the features of hepatobiliary subtype. CLC of the true meaning which must have originated from cholangiole may be identified by the following criteria: the size of the cancer duct (smaller than 15 μm), positivity for c-Kit, and absence of an ordinary ICC component.

Most liver tumors are benign and hypervascular, and it is important to avoid unnecessary interventions for benign lesions. This review describes the typical and atypical imaging features of common hypervascular benign liver tumors and outlines a general approach to distinguishing between benign and malignant hepatic lesions. There are many types of benign liver tumors that need to be differentiated from hepatocellular carcinoma (HCC). Therefore, it is very important to know the imaging characteristics of benign tumors. Gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging is helpful in diagnosing hypervascular pseudotumors, focal nodular hyperplasia, and nodular lesions associated with alcohol-induced hepatitis. There are also some hypervascular malignant tumors, such as cholangiocarcinoma, cholangiolocellular carcinoma, mixed type tumors, and metastatic liver tumors, which also required differentiation from HCC.

To review the gadoxetic acid disodium (EOB)-enhanced magnetic resonance (MR) imaging features of cholangiolocellular carcinoma (CoCC) of the liver and compare them with those of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). EOB-enhanced MR images of 19 patients with CoCC, 23 with ICC, and 51 with HCC were retrospectively evaluated qualitatively and quantitatively. Univariate and multivariate analyses were performed to determine the characteristic MR features of CoCC with histopathological–imaging correlation. Multivariate logistic regression analysis showed that dot-/band-shaped internal enhancement during the arterial and portal phases (P

We report a case of combined hepatocellular-cholangiocarcinoma with stem cell features, cholangiolocellular subtype arising about 15 years after placement of an inferior vena cava stent for primary Budd–Chiari syndrome. Pre-surgical differentiation of the tumor from hepatocellular carcinoma was difficult because of elevated levels of alpha-fetoprotein and hypervascularity in the arterial phase. Histopathological examination revealed atypical cells forming ductal and alveolar structures showing a vague border with the surrounding liver. Immunostaining showed positive results for epithelial membrane antigen, mainly localized to the apical surface of the tubules, representing a characteristic finding for combined hepatocellular-cholangiocarcinoma with stem cell features, cholangiolocellular subtype. Combined hepatocellular-cholangiocarcinoma with stem cell features arising in the liver with hepatic damage from Budd–Chiari syndrome is not common, but diagnosis is important to manage the malignancy, which shows different clinical behaviors from hepatocellular carcinoma.

Synchronous double cancers consisting of hepatocellular carcinoma (HCC) and cholangiolocellular carcinoma (CoCC) are extremely rare. We herein report a surgical case of synchronous double cancers in a patient with primary HCC and CoCC. A 45-year-old man with hepatitis B was admitted to our hospital with hepatic tumors. The level of protein induced by vitamin K antagonist (PIVKA-II) was found to be elevated. Computed tomography (CT) revealed a 23-mm tumor with early-phase enhancement and late-phase washout in the 6th segment of the liver, and a 10-mm tumor with slight early-phase enhancement and late-phase washout in the 7th segment of the liver. Magnetic resonance imaging (MRI) revealed that the two tumors in the 6th and 7th segments showed low intensity on T1-weighted images and high intensity on T2-weighted images. Based on those preoperative examinations, the liver tumors were diagnosed as multiple primary hepatocellular carcinomas. The patient underwent a posterior segmentectomy. A histopathological examination revealed that the tumor of the 6th segment of the liver was moderately differentiated HCC, and that the tumor of the 7th segment of the liver was CoCC. The postoperative course was uneventful. However, lymph node recurrence was observed 6 months later and the patient died 20 months after surgery. There are only six reported surgical cases of synchronous double primary liver cancers consisting of HCC and CoCC. We are of the opinion that curative resection may be an effective treatment for double cancer consisting of HCC and CoCC, and that it may provide long-term survival.

Purpose Cholangiolocellular carcinoma (CLC) is an extremely rare malignant liver tumor. It is thought to originate from the ductules and/or canals of Hering, where hepatic stem cells (HpSC) are located, but there are few reports on cancer stem cell markers in CLC. Thus, we evaluated the significance of cancer stem cell markers, including CD133, CD44, and EpCAM, in CLC. Methods The subjects of this study were three patients with CLC and one patient with an intermediate type of combined hepatocellular cholangiocarcinoma (CHC). The cancer cell markers, CK7, CK19, and EMA, were evaluated immunohistochemically. Results Histological examination of the CLC revealed morphologically cholangiolar features and immunohistochemical examination revealed positivity for CD133, CD44, and EpCAM. On the other hand, in the intermediate type of CHC, only CD44 was positive, whereas CD133 and EpCAM were negative. Conclusion CLC may have stronger features derived from HpSCs than an intermediate type of CHC.

Background/purpose The origin of cholangiolocellular carcinoma (CoCC) is still controversial. To solve this problem, morphometric and immunohistochemical features of CoCC were examined. Materials and methods Cancerous ducts: 15 CoCC lesions from 13 resected and two autopsied cases. Non-neoplastic ducts: 20 specimens of non-cancerous areas of eight resected CoCC cases and of 12 resected hepatocellular carcinoma (HCC) cases. From these specimens, cholangioles, interlobular ducts of small size (ILD-S), interlobular ducts of medium size (ILD-M) and septal ducts were randomly selected. Morphometry The outer and inner diameters of these ducts were measured. Immunohistochemistry: two hepatocyte markers [Hep Par 1 and α-fetoptotein (AFP)], two cholangiocyte markers (cytokeratin CK7, CK19), a marker for mucin (Muc1), a hepatic stem/progenitor cell marker (c-Kit) and epithelial membrane antigen (EMA) were used. Results Morphometry: both mean values of the outer and inner diameters of CoCC were far larger than those of cholangioles, and showed intermediate values between those of ILD-S and ILD-M. Immunohistochemistry: all ducts of CoCCs were negative for the two hepatocyte markers and positive for CK 7. Most CoCC ducts were positive for CK 19. Positive rate of c-Kit of cholangiole was most remote from that of CoCC. The positive rates of EMA in the membranous area of ducts were similarly very high in CoCC, cholangiole and ILD-S. Conclusion These results suggest that CoCCs may originate from ILDs.

細胆管細胞癌は肝幹細胞由来の稀な腫瘍である．今回，われわれは典型例を経験したので画像所見と病理所見を提示する．症例は61歳，男性．腹部dynamic CTにて肝S7に動脈相で辺縁が優位に造影され平衡相で造影効果が遷延し内部が造影される最大径45mmの腫瘤影が認められた．腹部超音波では低エコー腫瘤として描出された．プリモビスト造影MRIではこの腫瘤は動脈相で辺縁が優位に造影され，肝細胞造影相では低信号に描出された．以上の所見から肝内胆管癌を疑い，肝S7亜区域切除術を施行した．腫瘍の病理組織像は細胆管に類似した小型腺管が密に増殖する高分化型腺癌であった．免疫染色にて腫瘍細胞はCK-7，CK-19，NCAMおよびEMAがいずれも陽性であり，細胆管細胞癌と確定診断された．肝内胆管癌と同様な造影パターンを示す腫瘍でも低エコー腫瘤であった場合は，鑑別診断として細胆管細胞癌も考慮すべきであったと考えられた．

症例は64歳の男性で，B型肝硬変経過観察中に肝腫瘤性病変を発見され入院した．血清AFP, PIVKA-II値が高値を示し，腹部CT, MRIで肝S8a, S8cに腫瘤性病変を認めた．造影ではS8cの結節は後期相まで濃染が持続し非典型的であったが，多発肝細胞癌と診断し手術を施行した．病理組織学的，免疫組織学的にS8aの腫瘍は肝細胞癌，S8cの腫瘍は細胆管細胞癌で，重複肝癌と診断された．肝細胞癌と細胆管細胞癌の重複肝癌の報告例は少なく，文献的考察を加え報告する．

症例は62歳の男性で，B型慢性肝炎のfollow up CTにて肝S8に腫瘤を指摘され，当科を紹介受診・入院となった．入院時検査にてHBs-Ag（＋），HCV-Ab（−）であり，腫瘍マーカーはAFP・PIVKA-IIともに上昇を認めた．画像診断と合わせて肝細胞癌の診断にて肝前区域切除を施行した．病理所見は腫瘤の多くは異型の強い核を持つ多形性～紡錘形の細胞が混在して増殖する肉腫様の組織と，その周囲の細胆管類似の管腔形態を示す組織であり，肉腫様変化を示した細胆管癌と診断した．術後経過は良好で通常通りに退院したが，術後3か月頃より残肝再発，傍大動脈リンパ節腫大を認め，肝不全により術後4か月で死亡した．肉腫様変化を伴う胆管癌はまれであり，さらに細胆管癌もまたまれな疾患である．その両者が混在した貴重な症例を経験したので報告した．

Objective Cholangiolocellular carcinoma (CLC) is a rare subtype of intrahepatic cholangiocarcinoma as categorized according to the World Health Organization criteria. Recent study also revealed that CLC would originate from hepatic progenitor cells, which are liver-specific stem cells. We reviewed the imaging findings of CLCs, including those of intrahepatic metastases. Methods Eight patients who underwent partial hepatectomy were included in this study. Images, including dynamic computed tomographic and magnetic resonance images, were reviewed. Results On arterial phase images, the lesions appeared as masses exhibiting early and complete enhancement or predominantly peripheral enhancement. Retention of the contrast media in the lesions was observed in half of the lesions. The metastatic nodules had indistinct borders and showed early enhancement along with delayed central enhancement. Conclusions Although CLC with dense central fibrosis exhibits imaging features similar to those exhibited by intrahepatic cholangiocarcinoma, early enhancement in most lesions with persistent delayed enhancement is one of the characteristic imaging findings of this rare tumor.

We here report the first case of cholangiolocellular carcinoma (CoCC) visualized with contrast-enhanced ultrasonography (CEUS) using a second-generation contrast agent, Sonazoid. A 76-year-old man was admitted to our hospital for evaluation of a hepatic tumor. The tumor was described as having hyper-enhancement in the early phase and persistent enhancement in the late phase by contrast-enhanced computed tomography (CT) and magnetic resonance imaging (MRI), as well as hypervascularity by angiography. CEUS assessment of the nodule showed diffuse and homogeneous enhancement in the pure arterial phase, which became progressively hypoechoic relative to the adjacent liver parenchyma during the portal vein and late phases (mixed vascular phase), and showed a contrast defect with an unclear border in the Kupffer phase. Histologically we diagnosed this hepatic tumor as CoCC. In light of the above findings and the rarity of CoCC, it is helpful to incorporate the results of several imagings, such as CT, MRI, angiography and CEUS with a second-generation contrast agent when clinically diagnosing CoCC.

症例はB型肝炎の既往がある59歳の男性で，肝S7-8に増大する径5 cmの腫瘍を指摘された．CTや血管造影検査では，腫瘍辺縁が早期に濃染したが中心部は造影されなかった．Cholangiocellular carcinoma（以下，CCC）の診断で肝右葉切除術が施行された．被膜形成のない白色充実性の硬い腫瘍で，cholangiolocellular carcinoma（以下，CoCC）以外にCCCやhepatocellular carcinoma（以下，HCC）の成分が混在していた．PAS（−），Alcian blue（±），サイトケラチン（以下，CK）-7（＋），CK-19（＋），CK-8（＋），Hep-Par1（−）であった．Epithelial membrane antigen（以下，EMA）の染色性から，CCCへの分化を伴うCoCCと診断された．術後に一旦正常化した腫瘍マーカーは，2年後に縦隔リンパ節転移や多発肺転移，癌性胸膜炎の出現とともに再上昇し，患者は術後3年3か月で死亡した．CoCCや混合型肝癌はいずれもhepatic progenitor cells由来と考えられており，同一の病態である可能性がある．

症例は70歳，男性．自覚症状なし．人間ドックの腹部エコーで肝S5に腫瘤性病変を指摘された．AFP;2305.2ng/ml，PIVKA-II;99mAU/mlと高値，HBV Ag(－)，HCV Ab(－)．腹部造影CTで肝S5に約6cm大の早期相で辺縁が不均一に造影され，遅延相においても造影効果が遷延する腫瘤を認めた．画像診断上，肝内胆管癌も鑑別として挙げられたが，AFP，PIVKA-II高値であることから術前診断を肝細胞癌として肝S5亜区域切除術を施行した．術後病理組織所見で細胆管細胞癌（cholangiolocellular carcinoma;CoCC）と診断され，免疫染色では一部AFP，Hep-Par1陽性部分も認められた．細胆管細胞癌は極めて稀な疾患であり，術前AFPが高値を示した報告例はわずかである．また本症例の病理組織学的特徴は過去に報告例がないため，文献的考察を加えて報告した．

症例は87歳の男性で，表在性膀胱癌のため当院泌尿器科で経尿道的腫瘍切除が行われ，経過観察されていた．2007年1月の腹部造影CTで肝S6に15 mmの腫瘤性病変が指摘されたが，血管腫と診断し経過観察されていた．2007年9月の腹部造影CTで肝S6の腫瘤性病変は30 mmに増大しており，胆管細胞癌（cholangiocellular carcinoma；以下，CCC）が疑われた．肝腫瘍生検にて中分化型のCCCと診断され，肝S6部分切除を行った．病理組織学的診断では，小型均一な癌細胞が索状から小管腔を形成し互いに癒合しながら増殖する像を呈しており，細胆管細胞癌（cholangiolocellular carcinoma；以下，CoCC）と診断された．術後12か月が経過したが無再発生存中である．極めてまれなCoCCの切除例を経験したので文献的考察を加えて報告する．

Cholangiolocellular carcinoma (CLC) is an extremely rare malignant liver tumor which was first defined by Steiner, et al . in 1957 (1). CLC is thought to be derived from Hering’s canal because tumor glands of CLC are morphologically similar to cholangioles. Recently, Theise, et al . reported that Hering’s canal might be composed of hepatic stem cells (3). In addition, CLC sometimes contains a hepatocellular carcinoma (HCC) or cholangiocellular carcinoma (CCC) component within the tumor. Those findings suggest that CLC might originate from hepatic stem cells. On the other hand, because of its low frequency, clinicopatholigical features of CLC have not been fully clarified yet. We herein report a case of a 71-year old man with CLC. Based on preoperative imagings, the hepatic tumor was diagnosed as HCC, and he underwent a partial hepatectomy. The tumor contained both a HCC and CCC-like area. In immunohistochemistry, cytokeratin (CK) 7, CK20, CAM5.2 was positive, and CK19 was negative, therefore the tumor was diagnosed as CLC. The diagnostic criteria have not been described clearly, so CLC is difficult to diagnose preoperatively. Further studies are needed to clarify the clinical and clinicopatholigical features of CLC.

症例は69歳，女性．C型慢性肝炎に対してペグインターフェロン（Peg-IFN）・リバビリン併用療法を施行．Peg-IFN開始前，肝S5領域に腹部超音波にて径10 mm大の低エコー結節を認め，Dynamic CTで周囲から中央へ濃染する腫瘍であり，肝血管腫として経過観察されていた．Peg-IFN終了後，肝S5領域の腫瘍が径15 mm大に増大を認めたために精査入院となった．Dynamic CTでは腫瘍辺縁が動脈相で濃染し，平衡相でwash outを認めるようになり，腫瘍中心部に非濃染部を持つ腫瘍へと変化していた．肝細胞癌（Hepatocellular carcinoma：HCC），あるいは胆管細胞癌（Cholangiocellular carcinoma：CCC）との混合型肝癌を強く疑い，肝右葉切除術を施行した．腫瘍は組織学的に小型細胞がスリット状の腺腔を形成し，間質には豊富な結合織を認め，免疫染色でCK7, CK19, CK19-9, EMAが陽性，HepPar-1が陰性，c-kitが一部陽性を示し，細胆管細胞癌（Cholangiolocellular carcinoma：CoCC）と診断した．近年，CoCCの報告は増加を認めるも，その臨床像，画像的特徴，組織学的特徴などは必ずしも明らかとは言えない．今回，小腫瘍として発見され，画像上造影所見の変化を認めたCoCCの一切除例を経験したので報告する．

症例は25歳，女性．右側腹部痛と発熱を主訴に近医受診，腹部超音波検査にて肝腫瘤を指摘され当院へ紹介入院となった．HBs抗原およびHCV抗体は陰性，軽度肝機能異常，軽度炎症所見を認めるのみで，腫瘍マーカーは正常範囲であった．CTでは，肝右葉を占める巨大腫瘍で，充実性部分と嚢胞性部分が混在しており，充実性部分は早期相で濃染，晩期相でwash outされる肝細胞癌様所見を呈し，嚢胞性部分辺縁は淡く造影され中心部は全く造影されず，血管造影では腫瘍血管の増生と口径の不整が見られた．悪性肝腫瘍と診断し肝右葉切除術を施行した．腫瘍割面は充実性部分と嚢胞性部分が混在し，病理組織検査にて，細胆管細胞に類似した腫瘍細胞が小管腔を形成し，cytokeratin 7が陽性で抗肝細胞抗体が陰性であり，細胆管細胞癌と診断された．術後17日目に退院し，補助療法は行なわず，術後4年の現在，無再発生存中である．

A subgroup of intrahepatic cholangiocarcinoma and combined hepatocellular- cholangiocarcinoma contain a component of cholangiolocellular carcinoma, which is composed of small bile ductular cells. Ductular reaction, a reactive lesion at the portal tract interface comprising increased bile ductules, is frequently seen in chronic advanced liver diseases. Bile duct adenoma, a benign tumor/tumorous lesion is also composed of bile ductular cells. Differential diagnosis among these bile ductular tumors/lesions is sometimes difficult. Given overexpression of a polycomb group protein EZH2 in intrahepatic cholangiocarcinoma and high expression of senescence-associated p16INK4a in ductular reactions, we plan to apply immunostaining for EZH2 and p16INK4a for differential diagnosis of these bile ductular tumors/lesions. The expression of EZH2 was seen in all cases of cholangiolocellular carcinomas, while it was not observed in bile duct adenomas or ductular reactions. In contrast, the expression of p16INK4a was seen in most bile duct adenomas and all ductular reactions, whereas it was barely seen in cholangiolocellular carcinomas. A borderline between cholangiolocellular carcinoma and the surrounding ductular reaction was clearly highlighted by the reverse expression pattern of EZH2 and p16INK4a. In conclusion, immunostaining for EZH2 and p16INK4a may be useful for differential diagnosis for bile ductular tumors/lesions.

Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver cancer. Cirrhosis and chronic viral hepatitis are known to be important risk factors for ICC, especially the mass-forming (MF) type of ICC at the periphery of the liver. Cholangiolocellular carcinoma (CoCC) is a rare type of primary liver cancer, which is thought to originate from hepatic progenitor or stem cells. CoCC often exhibits the similar MF type at the periphery of the liver, as ICC, and CoCC is also associated with cirrhosis or chronic viral hepatitis. Better survival rates after surgery have been reported for ICC patients with chronic viral hepatitis than for those without chronic viral hepatitis, although survival rates did not differ significantly in relation to cirrhosis. On the other hand, patients with CoCC had better surgical results than those with MF-type ICC. This review summarizes the clinical characteristics and surgical outcomes of ICC and CoCC associated with cirrhosis or chronic viral hepatitis.