Journal of Liver Cancer

Review Articles

Combined hepatocellular-cholangiocarcinoma: a contemporary pathologic and molecular perspective: Taek Chung; J Liver Cancer. 2026;26(1):1-8. Published online March 9, 2026; DOI: https://doi.org/10.17998/jlc.2026.03.06

2,432 Views
112 Downloads
1 Citation

Combined hepatocellular cholangiocarcinoma (cHCC-CCA) is a rare primary liver carcinoma characterized by the unequivocal coexistence of hepatocytic and cholangiocytic differentiation within a single tumor. Despite its low incidence, cHCC-CCA has received considerable attention because of its marked histologic heterogeneity, diagnostic challenges, and poorer clinical outcomes than conventional hepatocellular carcinoma. Historically, the biological nature of cHCC-CCA has been controversial, with competing hypotheses, including derivation from hepatic progenitor cells, collision of independent tumors, and transdifferentiation between hepatocytic and biliary lineages. Recent advances in genomic and transcriptomic profiling have substantially improved this understanding. Accumulating evidence indicates that most cHCC-CCAs arise from a common clonal origin and subsequently undergo divergent differentiation rather than representing true collision tumors. Transcriptomic analyses further demonstrate that cHCC-CCAs span a biological continuum between hepatocellular- and cholangiocytic-like states, with intermediate tumors characterized by lineage plasticity, activation of developmental pathways, and heterogeneous tumor microenvironments. This review provides a pathology- centered overview of cHCC-CCAs, summarizing the key histopathological features and the supportive role of immunohistochemistry, followed by an integrated discussion of recent genomic, transcriptomic, and immune profiling studies. Additionally, it highlights emerging applications of artificial intelligence and digital pathology, which may assist in biological stratification. Collectively, the current evidence supports viewing cHCC-CCA not as a single static entity, but as a spectrum of primary liver carcinomas unified by lineage plasticity, underscoring the importance of integrated pathological and multi-omics approaches for future classification and research.

Citations

Citations to this article as recorded by

Curative Effect Evaluation of Targeted Therapy and Chemotherapy for Non-Resectable Combined Hepatocellular-Cholangiocarcinoma: A Systematic Review and Meta-Analysis
永豪林
Advances in Clinical Medicine.2026; 16(05): 920. CrossRef

Imaging differentiation of hepatocellular carcinoma, combined hepatocellular-cholangiocarcinoma, and intrahepatic cholangiocarcinoma: pitfalls and advances: Jaeseung Shin, Taek Chung, Sang Yun Ha, Hyungjin Rhee; J Liver Cancer. 2026;26(1):9-18. Published online March 5, 2026; DOI: https://doi.org/10.17998/jlc.2026.03.05

6,870 Views
126 Downloads

Abstract PDF: Accurate non-invasive differentiation of primary liver cancers, such as hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (iCCA), and combined hepatocellular-cholangiocarcinoma (cHCC-CCA), is crucial for optimal management but challenging due to shared risk factors and overlapping imaging phenotypes. While the Liver Imaging Reporting and Data System category M effectively captures the classic targetoid appearance of large duct type iCCA, the small duct type frequently exhibits HCC-mimicking non-rim arterial phase hyperenhancement and non-peripheral washout, potentially compromising diagnostic specificity. Furthermore, cHCC-CCA presents a formidable diagnostic dilemma, existing on a continuous imaging spectrum that reflects its histologic dominance. This continuous imaging spectrum not only blurs radiologic distinctions but also complicates tissue sampling, limiting the diagnostic accuracy of core needle biopsies and highlighting the risk of misclassification. To enhance diagnostic clarity, this review highlights their key imaging hallmarks: while HCC typically shows non-rim arterial phase hyperenhancement (APHE) and non-peripheral washout, large duct iCCA displays a classic targetoid appearance with rim APHE and progressive central enhancement. Conversely, small duct iCCA often mimics HCC, and cHCC-CCA exhibits a variable spectrum depending on its predominant histologic component. Ultimately, overcoming these diagnostic pitfalls requires a rigorous, multidisciplinary approach that synthesizes imaging findings, serologic tumor markers, and clinical contexts.

Contemporary overview of liver transplantation for intrahepatic cholangiocarcinoma and combined hepatocellular-cholangiocarcinoma: Hae Won Lee; J Liver Cancer. 2026;26(1):29-35. Published online March 5, 2026; DOI: https://doi.org/10.17998/jlc.2026.03.03

1,914 Views
62 Downloads

Abstract PDF: Historically, intrahepatic cholangiocarcinoma (iCCA) and combined hepatocellular-cholangiocarcinoma (cHCC-CCA) were regarded as absolute contraindications for liver transplantation (LT) due to dismal outcomes characterized by high recurrence rates and poor long-term survival in early experiences. Consequently, these malignancies have been systematically excluded from standard transplant criteria for decades. However, the landscape of transplant oncology is undergoing a significant paradigm shift, driven by a deeper understanding of tumor biology and refined patient selection strategies. Recent multicenter retrospective studies have identified a distinct subgroup of patients-specifically those with “very early” iCCA in the setting of cirrhosis-who achieve excellent post-transplant outcomes comparable to those of hepatocellular carcinoma. This evidence has prompted major international societies to update their guidelines, cautiously opening the door for LT in this selected population. Conversely, cHCC-CCA remains a diagnostic and therapeutic challenge. This narrative review critically analyzes the pivotal data driving the current paradigm shift and synthesizes the latest clinical practice guidelines to provide a contemporary roadmap for the management of iCCA and cHCC-CCA in the transplant setting.

Case Report

A Case of Combined Hepatocellular-cholangiocarcinoma Mimicking Pyogenic Liver Abscess: Seung Suk Baek, Eileen L. Yoon, Hyun-Jung Kim, Kyung Eun Bae, Kyeongmee Park, Won-choong Choi; J Liver Cancer. 2017;17(2):174-181. Published online September 30, 2017; DOI: https://doi.org/10.17998/jlc.17.2.174

4,168 Views
43 Downloads

Abstract PDF: Heterogeneous features of liver cancer can mimic liver abscess. Therefore it is essential to doublecheck tumor markers in the diagnosis of liver abscess. Herein, we report a case of combined hepatocellular-cholangiocarcinoma (cHC) occurred in an unrecognized chronic hepatitis B patient initially misdiagnosed as liver abscess. A 49-year old male initially presented with chill, right upper quadrant pain, and a liver mass. Mass showed peripheral enhancement in arterial phase of computed tomography, which was not typical for hepatocellular carcinoma (HCC). Strikingly elevated alpha-fetoprotein and fine needle aspirated pathology revealed HCC. Despite discordant image findings he was treated with transarterial chemoembolization. He was treated with sorafenib due to metastatic retrocaval lymphadenopathy afterwards. The mass presumed to be HCC progressed with sorafenib. It was surgically resected and he was finally confirmed as cHC. Discordant tumor markers with presumptive image findings should prompt the suspicion of rare type of primary liver cancer, the cHC.

Review Articles

Tumorigenesis of Combined hepatocellular and cholangiocarcinoma: Si Hyun Bae; Journal of the Korean Liver Cancer Study Group. 2007;7(1):8-12. Published online June 30, 2007

1,671 Views
2 Downloads

Abstract PDF: Combined hepatocellular-cholangiocarcinoma (CHC) is an extremely rare form of primary liver cancer having features of both hepatocellular and biliary epithelial differentiation. The incidence of CHC was 1.0-6.3% of all primary liver cancers. Since Allen and LIsa first described the features of this tumor in 1949, Allen’s classification has been widely used. This classification includes: type A, double cancer of HCC and CC, with HCC and CC present at different sites without contact; type B, HCC and CC are present at adjacent sites and mingle with continued growth; and type C, HCC and CC are mixed, growing within the same tumor. CHC are often confused with pseudoglandular growth pattern in HCC, but this has led to the mistaken impression that CHC are common. Histologically, only type C displays the characteristic of genuine mixture of both HCC and CC elements, and only Allen’s type C was included and regarded as true CHC in many published studies of CHC. With regard to the tumorigensis of CHC, the following possibilities have been proposed: 1st, the CC component arises from the main HCC tumor, and 2nd, the entire cancer arises from a stem cell potentially differentiating into hepatocytes and bile duct epithelium. In this review, I will describe the tumorigenesis of CHC and introduce the hepatic stem cell, such as hepatic progenitor cells.

Radiology of the Combined HCC and CC: Jin-Young Choi; Journal of the Korean Liver Cancer Study Group. 2007;7(1):16-21. Published online June 30, 2007

1,532 Views
18 Downloads

Abstract PDF: Combined hepatocellular-cholangiocarcinoma (HCC-CC) is a rare tumor showing histological evidence of both hepatocellular and biliary epithelial differentiation. Because of its rarity, there have been few reports about the imaging findings of this tumor. The CT findings of the combined HCC-CC include well-defined tumor with signs of malignancy such as hepatic hypervascularity, biliary obstruction, satellite nodules, and lymphadenopathy. Some portions may show hypoattenuation on arterial phase, whereas other portions show delayed persistent enhancement. The signal intensity of this tumor on magnetic resonance (MR) imaging is not specific. However, when the tumor resembles cholangiocarcinoma on gross pathologic exam, it shows peripheral rim-like enhancement, infiltrative margin, and portal vein invasion in patients with liver cirrhosis. On the other hand, when the tumor has gross appearance of HCC, imaging findings are not helpful for diagnosis. Cross-sectional imagings are helpful for predicting the predominant component of the combined HCC-CC and determining the treatment strategy.

Surgical treatment of combined hepatocellular and cholangiocarcinoma: Chul Soo Ahn; Journal of the Korean Liver Cancer Study Group. 2007;7(1):22-27. Published online June 30, 2007

1,298 Views
4 Downloads

Abstract PDF: Combined hepatocellular and cholangiocarcinoma (HCC-CC) is an uncommon form of primary liver cancer (PLC) with features of hepatocellular and biliary epithelial differentiation. According to publishing records HCC-CC accounts for 0.4% to 14.2% of all PLC cases. Large number of HCC-CC is associated with chronic viral hepatitis or cirrhosis, especially in asian countries. The tumor markers of HCC-CC (AFP, CA19-9) shows the intermediate level between hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC). The clinical features of HCC-CC resembled with HCC but its post operative result and metastatic pattens are similar to that of CC. Surgical results of this tumor can yield results that are intermediate between HCC and CC in characteristics. But complete resection is the only effective therapy and can result in long term survival. And there are hot debates for the additional hilar lymph node dissection. The survival rate of HCC-CC is higher than CC but lower than HCC. The recurrence after resection has been frequently reported. Most of them are intrahepatic recurrences as HCCs but extrahepatic recurrences are much more frequent like CC. The CC component of HCC-CC seem to determine the prognosis. So more effective approaches for treating recurrent disease, such as local ablation therapy and or combination systemic chemotherapy and neoadjuvant chemoradiation, should be applied for long term and better results.

Case Report

A Case of Combined Hepatocellular-Cholangiocarcinoma: Kee Sup Song, Young Saeng Kim, Uk Sun Chang, Oh Sang Kwon, Yun Soo Kim, Duck Ju Choi, Ju Hyun Kim, Ha Na Kim, Jee Hee Kang, Jung Ho Kim, Jae Hong Park, Dong Hae Jung, Keon Kuk Kim; Journal of the Korean Liver Cancer Study Group. 2007;7(1):98-102. Published online June 30, 2007

1,053 Views
2 Downloads

Abstract PDF: Combined hepatocellular-cholangiocarcinoma (HCC-CC) is a rare form of primary liver cancer, featuring both hepatocellular and biliary epithelial differentiation. A 49-year-old man who was chronic HBV carrier complained of generalized weakness for 1 month. Abdominal CT scan and MRI showed a 3 cm-sized, hypodense mass in S6 of the liver with contrast enhancement. Percutaneous ultrasound-guided core needle biopsy of the liver yielded HCC-CC, and transarterial chemoembolization was done. Abdominal CT scan taken 2 weeks after TACE showed a partial uptake of lipiodol and then he underwent right posterior segmentectomy. The surgical specimen showed complete necrosis and no viable tumor cell. He was discharged without any complication.

First
Prev
Page of 1
Next
Last

Search