Cholangiocarcinoma Components Research Articles

Is it necessary to distinguish between combined hepatocellular carcinoma-cholangiocarcinoma with less than 10% of cholangiocarcinoma components versus hepatocellular carcinoma?

Is it necessary to distinguish between combined hepatocellular carcinoma-cholangiocarcinoma with less than 10% of cholangiocarcinoma components versus hepatocellular carcinoma?

Clinicopathological features and recurrence patterns of combined hepatocellular-cholangiocarcinoma

BackgroundCombined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a primary liver carcinoma with both hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) components. We examined the clinicopathological characteristics and recurrence patterns of cHCC-CCA. Because of the rarity of cHCC-CCA, its etiology, clinicopathological features, and prognosis in comparison with other primary liver carcinoma remain unknown. Its recurrence pattern and sites in particular also need to be elucidated.MethodsAll patients who underwent hepatectomy for primary liver malignancies between 2005 and 2015 were retrospectively included in this study.ResultsEight hundred and ninety-four hepatectomies were performed. Nineteen cases of cHCC-CCA (2.1%) in 16 patients were enrolled. Three patients underwent re-hepatectomy. The background of hepatitis viruses and tumor marker patterns of cHCC-CCA were similar to those of HCC and dissimilar to those of intrahepatic CCA (iCCA). Biliary invasion was common in cHCC-CCA and iCCA. The 5-year overall survival values of the cHCC-CCA, HCC, and iCCA patients were 44.7%, 56.6%, and 38.5%, respectively. The 5-year recurrence-free survival values of the cHCC-CCA, HCC, and iCCA patients were 12.2%, 28.7%, and 32.9%, respectively. The liver was the most common recurrence site. Unlike HCC, however, the lymph node was the second-most common recurrence site in both cHCC-CCA and iCCA. Pathological samples of the recurrent lesions were obtained in six patients, and four had cHCC-CCA recurrence pathologically.ConclusioncHCC-CCA had a mixture of characteristics of HCC and iCCA. Many cases of cHCC-CCA remained cHCC-CCA pathologically even after recurrence.

Activation of the Akt/mammalian target of rapamycin pathway in combined hepatocellular carcinoma and cholangiocarcinoma: significant correlation between p-4E-BP1 expression in cholangiocarcinoma component and prognosis.

The Akt/mammalian target of rapamycin (mTOR) pathway, which plays an important role in regulating cellular functions including proliferation, motility, and invasion, is known to be activated in many cancers. Combined hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) (cHCC-CC) has wide histological diversity characterized by relatively poor prognosis. Because of a lack of investigation into its molecular mechanisms, no effective systemic therapy is currently available for unresectable cHCC-CC tumors. Here, we retrospectively examined the clinicopathological and activation statuses of the Akt/mTOR pathway in 89 cases of cHCC-CC. Expression levels of molecular markers associated with this signaling pathway, including phosphatase and tensin homologue deleted on chromosome 10 (PTEN), phosphorylated Akt (p-Akt), p-mTOR, p-ribosomal protein S6 (p-S6RP), and p-eukaryotic translation initiation factor 4E (eIF4E)-binding protein 1 (p-4E-BP1), were measured by immunohistochemical staining. In addition, such activation in different cHCC-CC morphological categories was compared by dividing cases into those with HCC (n = 86), CC (n = 78), and intermediate components (n = 60). Comparison of prognosis among these groups revealed that p-4E-BP1 immunopositivity in cHCC-CC cases containing CC a component was a significant risk factor for poorer overall survival (P = 0.041). By evaluating factors in p-4E-BP1 expression in 78 cHCC-CC cases with a CC component, only lymph node metastasis was significantly correlated with positive immunostaining for p-4E-BP1 (P = 0.0222). In conclusion, p-4E-BP1 expression, especially in cHCC-CC cases with a CC component, was a notable Akt/mTOR pathway-related factor associated with poor prognosis. Assessing histological structure and p-4E-BP1 expression in cHCC-CC may be helpful for both predicting prognosis and using molecular targeted therapy.

83P - Comparing clonality between components of combined hepatocellular carcinoma and cholangiocarcinoma by targeted sequencing

Background: Combined hepatocellular-cholangiocarcinoma (cHCC-CC) is a very rare tumor. It has two different components (hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC)) in a single mass. Although several studies have determined genetic characteristics of cHCC-CC, Next-generation sequencing (NGS) data for comparing clonality of cHCC-CC are currently unavailable. Methods: We selected four cHCC-CC cases and micro-dissected HCC, CC, and normal components separately from each case. DNA and RNA were isolated from each sample and sequenced by Oncomine Comprehensive Panel (OCP) interrogating 143 cancer genes using Ion S5 XL sequence platform. Genetic features of HCC and CC from each patient were compared. Results: All cases successfully produced NGS data. Two cases demonstrated different mutations between HCC and CC components (biclone) while two cases shared the same mutations between two components (monoclone). SNPs of TP53 (4/4) and PTEN (1/4) and gene amplifications of MET (1/4), c-MYC (1/4), and CDK6 (1/4) were found in CC component. In HCC component, SNPs of TP53 (3/4), PTEN (1/4) and CTNNB1 (1/4) and CCND1 amplification (1/4) were detected. Two biclonal cases showed histologically distinguished border between HCC and CC components with or without intermediate cell foci. Two monoclonal cases showed histologically ambiguous border between HCC and CC components with more intermingled pattern than biclonal cases. Conclusions: We compared genetic compositions of HCC and CC components and matched clonality with histologic feature in cHCC-CC using targeted sequencing. Two (50%) of four cases had different clones between HCC and CC components with more distinguished histologic features than monoclonal cases. Considering such heterogeneity, partly sequencing is recommended for cHCC-CC, especially in those who have histologically distinguished HCC and CC components regardless of the presence of intermediate component. Legal entity responsible for the study: Nara Yoon. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.

Imaging features of combined hepatocellular–cholangiocarcinoma on contrast-enhanced ultrasound: correlation with clinicopathological findings

To evaluate the relationship between the imaging features of combined hepatocellular-cholangiocarcinoma (CHC) on contrast-enhanced ultrasound (CEUS) and clinicopathological findings. From August 2004 to August 2016, 40 patients (29 males, 11 females; mean age 52.8±11.2 years) with histopathologically proven CHC were investigated. The CEUS imaging features and clinicopathological findings of CHC were analysed and compared retrospectively. On CEUS, peripheral irregular rim-like enhancement, diffuse heterogeneous enhancement, and diffuse homogeneous enhancement was illustrated in 13 (32.5%), 21 (52.5%), and six (15%) lesions, respectively. Histopathological findings showed hepatocellular carcinoma (HCC) predominance and cholangiocarcinoma (CC) predominance throughout the tumour were illustrated in 21 (52.5%) and 19 (47.5%) cases, respectively. HCC-predominant CHCs displayed diffuse heterogeneous enhancement more frequently than peripheral irregular rim-like enhancement (p=0.005), whereas CC-predominant CHCs displayed peripheral irregular rim-like enhancement more frequently than diffuse heterogeneous enhancement and homogeneous enhancement (p=0.005 and p=0.01, respectively). CHCs >5 cm displayed diffuse heterogeneous enhancement more frequently than diffuse homogeneous enhancement, whereas CHCs ≤5 cm displayed diffuse homogeneous enhancement more frequently than diffuse heterogeneous enhancement (p=0.004). The enhancement pattern of CHC on CEUS depended on the relative proportionsof the HCC and CC components and showed size-dependent characteristics.

Clinicopathologic features of combined hepatic carcinoma

To investigate clinicopathological features of combined hepatocellular-cholangiocarcinoma (C-HCC-CC) with neuroendocrine carcinoma (NEC) differentiation and to review the literature. The clinical data, histological manifestations and immunohistochemical staining results of two cases of C-HCC-CC were analyzed along with a review of the current literature. Both patients were male with an average age of 57.5 years. Both patients were positive for hepatitis B virus antigen. The tumors of both cases demonstrated the following 3 unequivocal mixed elements: (1) polygonal epithelial tumor cells growing in nests or trabeculae with positive staining for Hepatocyte and AFP, diagnostic of hepatocellular carcinoma (HCC). Cytoplasmic bile production was present in the tumor cells in one case; (2) elliptic or short spindle-shape small blue tumor cells growing in nests or organoid pattern with Syn/CgA/CD56 positivity confirming the presence of neuroendocrine carcinoma (NEC) component; (3) oval tumor cells growing in nests or glandular forms with positivity of CK19 and CK7 confirming differentiation of cholangiocarcinoma (CC). In both cases, the tumors contained at least 20% of each of HCC, NEC and CC components. C-HCC-CC with NEC is a rare form of primary malignancy of the liver with a poor prognosis.

Hilar cholangiocarcinoma and pancreatic ductal adenocarcinoma share similar histopathologies, immunophenotypes, and development-related molecules

Embryologically, intrahepatic small bile ducts arise from hepatic progenitor cells via ductal plates, whereas the pancreato-extrahepatic biliary progenitor cells expressing the transcription factors PDX1 and HES1 are reportedly involved in the development of the extrahepatic biliary tract and ventral pancreas. The expression of cellular markers characteristic of the different anatomical levels of the biliary tree and pancreas, as well as PDX1 and HES1, was examined in cholangiocarcinoma components of combined hepatocellular cholangiocarcinoma (12 cases), intrahepatic cholangiocarcinoma (21 cases), hilar cholangiocarcinoma (25 cases), and pancreatic ductal adenocarcinoma (18 cases). Anterior gradient protein-2 and S100P were frequently expressed in hilar cholangiocarcinoma and pancreatic ductal adenocarcinoma, whereas neural cell adhesion molecule and luminal expression of epithelial membrane antigen were common in cholangiocarcinoma components of combined hepatocellular cholangiocarcinoma. PDX1 and HES1 were frequently and markedly expressed in pancreatic ductal adenocarcinoma and, to a lesser degree, in hilar cholangiocarcinoma, although their expression was rare and mild in cholangiocarcinoma components in combined hepatocellular cholangiocarcinoma. The expression patterns of these molecules in intrahepatic cholangiocarcinoma were intermediate between those in hilar cholangiocarcinoma and cholangiocarcinoma components of combined hepatocellular cholangiocarcinoma. Pancreatic ductal adenocarcinoma and hilar cholangiocarcinoma had a similar expression of mucin, immunophenotypes, as well as transcription factors. Pancreatic ductal adenocarcinoma and hilar cholangiocarcinoma showed similar postoperative prognosis. In conclusion, the similar expression of phenotypes related to pancreatobiliary anatomy and embryology may in part explain why these 2 types of carcinoma present similar clinicopathologic features. Further studies on the carcinogenesis of these carcinomas based on their similarities are warranted.

Expression of both hepatocellular carcinoma and cholangiocarcinoma phenotypes in hepatocellular carcinoma and cholangiocarcinoma components in combined hepatocellular and cholangiocarcinoma

Expression of phenotype markers of hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) in HCC and CC components of 20 combined hepatocellular and cholangiocarcinomas (CHCs) of the liver was investigated immunohistochemically. Both HCC and CC components of all CHCs expressed at least one of the CC phenotype markers [cytokeratin (CK)-7, CK-19, and carbohydrate (CA) 19-9]. HCC components in 90% of CHCs and CC components in 95% of CHCs expressed at least one of these CC phenotype markers in more than 40% of cancer cells. HCC components in all CHCs expressed at least one of the HCC phenotype markers [hepatocyte antigen (HA), α-fetoprotein (AFP), and canalicular carcinoembryonic antigen]. HCC components in 90% of CHCs and CC components in 75% of CHCs expressed HA, AFP, or both. HCC components in 75% of CHCs and CC components in 60% of CHCs expressed HA, AFP, or both in more than 10% of cancer cells. The present results show that both HCC and CC components of most of the CHCs expressed both HCC and CC phenotypes, supporting the hypothesis that CHC originates from a hepatic progenitor cell capable of differentiating into hepatocytes and cholangiocytes.

Copy number aberrations in combined hepatocellular carcinoma and cholangiocarcinoma

Combined hepatocellular carcinoma and cholangiocarcinoma (CHC) is a rare liver cancer which shares unequivocal features of both hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC). A greater awareness of genetic relationship between HCC and CC components is limited. To help characterize this rare liver neoplasm, we described clinicopathologic features and evaluated copy number (CN) changes in this study. A total of 13 cases of CHC were collected. Four paired HCC and CC components from four cases were first subject to genome-wide analysis. Nine target genes were subsequently selected for further analysis using quantitative polymerase chain reaction. The paired HCC and CC components in each case had a concordant trend of CN gain or loss in these nine genes. However, the magnitude of concordant CN gain or loss was different. There were significant differences of CN copies between HCC and CC in each case. We demonstrate genetic divergence between HCC and CC components in CHC.

Glypican-3 is a useful diagnostic marker for a component of hepatocellular carcinoma in human liver cancer

Primary liver cancers are classified into three types based on their morphology and cytogenetic characteristics hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC) and combined hepatocellular and cholangiocarcinoma (CHC). It is often difficult to distinguish these liver tumors. Glypican-3 (GPC3) is serological and histochemical marker of hepatocellular carcinoma. In order to separate these three types of liver cancers, we analyzed the GPC3 expression in 85 liver resection specimens, including 46 HCCs, 28 ICCs and 11 CHCs. GPC3 immunohistochemical staining was used to distinguish HCC from ICC by comparing with the conventional biomarker, alpha-fetoprotein (AFP). The immunostaining of GPC3 was identified in 78.3% (36/46) of HCCs, 60% (9/15) of well differentiated, 88.9% (16/18) of moderately differentiated and 84.6% (11/13) of poorly differentiated HCCs. It was negative in the ICCs. We confirmed that GPC3 expression is specific to HCC component (8/11, 72.7%) but few samples also showed weakly in ICC component (2/11, 18.2%) of CHC sections among 11 cases compared with HCC biomarkers including AFP and hepatocyto paraffin 1 (HepPar1), and ICC biomarkers cytokeratin (CK) 7 and CK19. Three cases in which the macroscopic features resembled ICC did not express GPC3 even in the pathological HCC component. Most (10/11, 91%) of the pathological cholangiocarcinoma components in CHC showed positive staining for CK7 and CK19. The results of this study suggest that GPC3 is a biomarker that is sensitive and specific to HCC component of CHC, and CK7 and CK19 are markers for pathological cholangiocarcinoma component of CHC.

A clinical study of 11 cases of combined hepatocellular–cholangiocarcinomaAssessment of enhancement patterns on dynamics computed tomography before resection

: The aim of this study was to identify computed tomography features that contribute to clinical diagnosis of hepatocellular-cholangiocarcinoma. : We retrospectively reviewed the clinicopathologic features of 11 patients who underwent hepatectomy for hepatocellular-cholangiocarcinoma between January 1994 and December 2003 at Hiroshima City Hospital and investigated correlation of histopathologic features of surgical specimens with preoperative enhanced computed tomography findings. : Three computed tomography enhancement patterns were observed: an area of hyperenhancement in the early phase and hypoenhancement due to washout of contrast medium in the late phase, resembling hepatocellular carcinoma (Type I, n=4); peripheral enhancement in the early and late phases (Type II, n=2); an area of hyperenhancement in the early phase and an area of slight delayed enhancement in the late phase (Type III, n=4). Histopathologically, all tumors were of mixed morphology (Allen's Type C) comprising hepatocellular carcinoma and cholangiocarcinoma components with transitional features. Computed tomography findings conformed well to pathologic findings. The hepatocellular carcinoma component was predominant in Type I masses. Type II masses showed central necrosis. In Type III masses, the hepatocellular carcinoma-predominant component corresponded to the area of early-phase enhancement and the cholangiocarcinoma-predominant component to the area of late-phase enhancement. : In Type III tumors, hepatocellular and cholangiocellular components can be identified on the basis of dynamic computed tomography enhancement pattern.

Hepatic 'stem cell' malignancies in adults: four cases.

Combined hepatocellular/cholangiocarcinomas have been explained by some investigators as bidirectional differentiation of neoplastic progenitor cell populations. The presence of hepatic progenitor cells has now been confirmed in humans, though whether they can give rise to malignant tumours has not been confirmed. We report four cases of small tumours identified in livers with features of chronic hepatitis which may suggest a role for malignant transformation of hepatic stem cells in hepatic malignancies. Tumour samples were studied from four patients by histochemistry and immunohistochemistry. Two patients had chronic hepatitis B, one had chronic hepatitis C and chronic alcoholic liver injury, and one had non-B non-C chronic hepatitis. Stages of disease ranged from portal fibrosis to cirrhosis. All tumours contained undifferentiated cells with morphological and immunohistochemical features that would be expected of hepatic progenitor cells. These cells merged with both hepatocellular carcinoma and cholangiocarcinoma components as well as with mature appearing hepatocytes within the tumours. We suggest that these tumours are of hepatic progenitor cell origin, supporting the concepts that human hepatocarcinogenesis can be based on transformation of progenitor cells and that such a process may underlie development of some mixed hepatocellular/cholangiocarcinomas and dysplastic nodules.

Microsatellite Instability in Intraductal Papillary Neoplasms of the Biliary Tract

Intraductal papillary neoplasms of the biliary tree are unusual lesions characterized by solitary or diffuse growth along the intra- and/or extrahepatic biliary tract. Biliary papillary neoplasms bear some clinicopathologic similarity to intraductal papillary mucinous neoplasms of the pancreas. Like intraductal papillary mucinous neoplasms of the pancreas, biliary papillary neoplasms can be purely intraductal lesions or can give rise to invasive adenocarcinomas. We recently studied the genetic alterations present in a series of biliary papillary neoplasms and noted the presence of allelic shifts in some biliary tumors during allelic loss assays on chromosomes 5q and 18q. This suggested that microsatellite instability might play a role in the molecular pathogenesis of biliary papillary neoplasms. Genomic DNA was extracted from 17 intraductal papillary neoplasms, 6 associated invasive cholangiocarcinomas, and corresponding normal tissues, and microsatellite instability testing was performed using the 5 microsatellite loci recommended by the 1997 National Cancer Institute–sponsored consensus conference (D2S123, D5S346, D17S250, Bat-25, and Bat-26). High-level microsatellite instability was considered to be present when at least two of five microsatellite loci showed allelic shifts, and low-level microsatellite instability, when only one locus was shifted, as per the National Cancer Institute criteria. We also determined the methylation status of the DNA mismatch repair gene hMLH1 by bisulfite treatment of genomic DNA, followed by methylation-specific PCR. High-level microsatellite instability was present in 2 of 17 (11.8%) biliary papillary neoplasms, including 1 case of purely intraductal tumor and 1 case with both intraductal and invasive cholangiocarcinoma components. In both cases there was extensive microsatellite instability, with allelic shifts in five of five and four of five microsatellite markers, respectively. Low-level microsatellite instability was present in 6 of 17 (35.3%) biliary papillary neoplasms, including 2 cases of purely intraductal tumor and 4 cases with both intraductal and invasive cholangiocarcinoma components. Interestingly, the pattern of allelic shifts was frequently not identical between the intraductal and invasive cholangiocarcinoma components; although the same microsatellite markers were shifted, alleles of differing lengths were generated in the intraductal and invasive components of the neoplasms with high-level microsatellite instability and of two neoplasms with low-level microsatellite instability. None of the biliary papillary neoplasms (0 of 10 cases with adequate DNA for evaluation) showed methylation of hMLH1. These results indicate that microsatellite instability is a relatively frequent event in papillary neoplasms of the biliary tree but is not associated with hMLH1 promoter hypermethylation. The finding that alleles of differing lengths were frequently generated between the intraductal and invasive components of those tumors with microsatellite instability suggests that there is significant genetic heterogeneity within these neoplasms.

The mode of tumour progression in combined hepatocellular carcinoma and cholangiocarcinoma: an immunohistochemical analysis of E-cadherin, alpha-catenin and beta-catenin.

To investigate the mode of progression of combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CC). An immunohistochemical study for E-cadherin (ECD) and alpha- and beta-catenins was performed on 29 cases of cHCC-CC. Reduced expression of ECD was significantly correlated with the tumour grade of the hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) components, intrahepatic metastasis (IM) of HCC, IM of CC, and vascular invasion of CC (p < 0.05, respectively). There was a significant relationship between the reduced expression of beta-catenin and the tumour grade of HCC components (p < 0.05). Cases showing concurrent intrahepatic metastasis composed of HCC, CC, or both, numbered 6, 5, and 2, respectively. The expression patterns of ECD and beta-catenin of IM were similar to those of primary lesion in most cases. On the other hand, expression of ECD and beta-catenin of IM of HCC component were preserved, even though those of the primary sites were reduced in two cases and one case, respectively. ECD and beta-catenin were significantly correlated with tumour differentiation and tumour progression. Preserved or recovered ECD and beta-catenin expression may be of beneficial effect for re-establishing the tissue architecture at the metastatic site.

Combined hepatocellular carcinoma and cholangiocarcinoma: Clinical features and computed tomographic findings

Clinicoradiological features were studied in 20 patients with 22 mass lesions of combined hepatocellular carcinoma and cholangiocarcinomas and findings of computed tomography in 12 of these patients with 14 hepatocellular carcinoma-cholangiocarcinomas. Five of these patients also had single overt hepatocellular carcinomas. The incidence of hepatocellular carcinoma-cholangiocarcinoma was 3.3% among the patients with primary liver cancer treated in our hospital. HBsAg was present in 25%, and increased levels of serum alpha-fetoprotein (> 200 ng/ml) and carcinoembryonic antigen (> 5 ng/ml) were found in 25% and in 47%, respectively. Associated cirrhosis was present in 60%. Analysis of 14 hepatocellular carcinoma-cholangiocarcinomas in 12 patients in whom the enhancement pattern on dynamic computed tomography and pathological findings could be studied and compared suggested three tumor types. Nine lesions (type A) were demonstrated only as areas with high-density peripheries in the early phase of enhancement that evolved into a pattern of peripheral low density and central high density in the late phase. Four masses (type B) were shown as hyperdense tumors (early phase) that changed to low density in the late phase. One mass (type C) was seen as a low-density lesion that did not change. Histopathologically, type A comprised hepatocellular carcinoma-predominant components in the peripheral area, cholangiocarcinoma-predominant components with abundant fibrous stroma in the central area and a tissue transitional between the two in the midzone. By contrast, two of four type B masses comprised hepatocellular carcinoma with scattered cholangiocarcinoma components throughout the tumor.(ABSTRACT TRUNCATED AT 250 WORDS)

Combined hepatocellular carcinoma and cholangiocarcinoma: Clinical features and computed tomographic findings

Clinicoradiological features were studied in 20 patients with 22 mass lesions of combined hepatocellular carcinoma and cholangiocarcinomas and findings of computed tomography in 12 of these patients with 14 hepatocellular carcinoma–cholangiocarcinomas. Five of these patients also had single overt hepatocellular carcinomas. The incidence of hepatocellular carcinoma–cholangiocarcinoma was 3.3% among the patients with primary liver cancer treated in our hospital. HBsAg was present in 25%, and increased levels of serum α-fetoprotein ( > 200 ng/ml) and carcinoembryonic antigen ( > 5 ng/ml) were found in 25% and in 47%, respectively. Associated cirrhosis was present in 60%. Analysis of 14 hepatocellular carcinoma–cholangiocarcinomas in 12 patients in whom the enhancement pattern on dynamic computed tomography and pathological findings could be studied and compared suggested three tumor types. Nine lesions (type A) were demonstrated only as areas with high-density peripheries in the early phase of enhancement that evolved into a pattern of peripheral low density and central high density in the late phase. Four masses (type B) were shown as hyperdense tumors (early phase) that changed to low density in the late phase. One mass (type C) was seen as a low-density lesion that did not change. Histopathologically, type A comprised hepatocellular carcinoma–predominant components in the peripheral area, cholangiocarcinoma-predominant components with abundant fibrous stroma in the central area and a tissue transitional between the two in the midzone. By contrast, two of four type B masses comprised hepatocellular carcinoma with scattered cholangiocarcinoma components throughout the tumor. The remaining two masses had main nodules of hepatocellular carcinoma and adherent small cholangiocarcinomas. One type C mass had a main cholangiocarcinoma nodule and an adjacent small hepatocellular carcinoma. Differentiation of hepatocellular carcinoma–cholangiocarcinoma from hepatocellular carcinoma or cholangiocarcinoma with computed tomography alone was difficult. When computed tomography results and α-fetoprotein or carcinoembryonic antigen levels show some discrepancy, the possibility of hepatocellular carcinoma–cholangiocarcinoma should be considered. (HEPATOLOGY 1993;18:1090-1095).