Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
BMC Cancer
Published in: BMC Cancer 1/2016

Open Access 01-12-2016 | Research article

Combined hepatocellular carcinoma and cholangiocarcinoma (biphenotypic) tumors: clinical characteristics, imaging features of contrast-enhanced ultrasound and computed tomography

Authors: Rui Li, Dan Yang, Chun-Lin Tang, Ping Cai, Kuan-sheng Ma, Shi-Yi Ding, Xiao-Hang Zhang, De-Yu Guo, Xiao-Chu Yan

Published in: BMC Cancer | Issue 1/2016

Login to get access

Abstract

Background

Combined hepatocellular-cholangiocarcinoma (cHCC-CC) is an uncommon primary liver malignancy and little known about the clinical and imaging characteristics of cHCC-CC. We aim to define the demographics, imaging features of cHCC-CC on contrast-enhanced ultrasound (CEUS) and contrast-enhanced computed tomography (CT) in this study.

Methods

From January 2005 to December 2014, 45 patients with pathologically proven cHCC-CC who underwent preoperative CEUS and 43 patients who had additional CT scan in our institution were included. A retrospective review of the imaging studies and clinical data in these patients was conducted.

Results

In our series, cHCC-CC accounted for 1.6 % of all primary liver malignancy. Mean age of patient with cHCC-CC was 52.8 year (range: 28–74 year) and 88.9 % (40/45) of patients were male. Thirty of forty five patients (66.7 %) had cirrhosis and 20 % (9/45) of patients had chronic hepatitis B without cirrhosis. Alpha--fetoprotein (AFP) was elevated in 62.2 % (28/45) of patients and carbohydrate antigen 19–9 (CA19-9) elevated in 22.2 % (10/45) of patients). Both AFP and CA19-9 were simultaneously elevated in 15.6 % (7/45) of patients. Enhancement pattern resembling cholangiocarcinoma (CC) was noted in 53.3 % (24/45) of patients (on CEUS and in 30.2 % (13/43) of patients at CT. Enhancement pattern resembling hepatocellular carcinoma (HCC) was observed in 42.2 % (19/45) of patients on CEUS and in 58.1 % (25/43) of patients at CT. The percentage of tumors showing CC enhancement pattern (27.9 %, 12/43) was comparable with that of tumors showing HCC enhancement pattern (44.2 %, 19/43) on both CEUS and CT (p = 0.116).
Simultaneous elevation of tumor markers (AFP and CA19-9) or tumor marker elevation (AFP or CA19-9) in discordance with enhancement pattern on CEUS was demonstrated in 51.1 % (23/45) of patients and on CT in 53.5 % (23/43) of patients, which was significantly more than simultaneous elevation of tumor markers (AFP and CA19-9) alone (p = 0.000).

Conclusions

The clinical characteristics of cHCC-CC are similar to those of HCC. The cHCC-CC tumors display enhancement patterns resembling CC or HCC in comparable proportion on both CEUS and CT. Combination of simultaneous elevation of tumor makers (AFP and CA19-9) and tumor mark elevation (AFP or CA19-9) in discordance with presumptive imaging findings on CEUS or CT may lead significantly more patients to be suspicious of the diagnosis of cHCC-CC.
Literature
1.
Lee WS, Lee KW, Heo JS, Kim SJ, Choi SH, Kim YI, Joh JW. Comparison of combined hepatocellular and cholangiocarcinoma with hepatocellular carcinoma and intrahepatic cholangiocarcinoma. Surg Today. 2006;36(10):892–7.
2.
Lee JH, Chung GE, Yu SJ, Hwang SY, Kim JS, Kim HY, Yoon JH, Lee HS, Yi NJ, Suh KS, et al. Long-term prognosis of combined hepatocellular and cholangiocarcinoma after curative resection comparison with hepatocellular carcinoma and cholangiocarcinoma. J Clin Gastroenterol. 2011;45(1):69–75.
3.
Allen RA, Lisa JR. Combined liver cell and bile duct carcinoma. Am J Pathol. 1949;25(4):647–55.
4.
Zhang F, Chen XP, Zhang W, Dong HH, Xiang S, Zhang WG, Zhang BX. Combined hepatocellular cholangiocarcinoma originating from hepatic progenitor cells: immunohistochemical and double-fluorescence immunostaining evidence. Histopathology. 2008;52(2):224–32.
5.
Itoyama M, Hata M, Yamanegi K, Yamada N, Ohyama H, Hirano H,Terada N, Nakasho K. Expression of both hepatocellular carcinoma and cholangiocarcinoma phenotypes in hepatocellular carcinoma and cholangiocarcinoma components in combined hepatocellular and cholangiocarcinoma. Med Mol Morphol. 2012;45(1):7–13.
6.
Fujii H, Zhu XG, Matsumoto T, Inagaki M, Tokusashi Y, Miyokawa N, Fukusato T, Uekusa T, Takagaki T, Kadowaki N et al. Genetic classification of combined hepatocellular-cholangiocarcinoma. Hum Pathol. 2000;31(9):1011–7.
7.
Kim H, Park C, Han KH, Choi J, Kim YB, Kim JK, Park YN:. Primary liver carcinoma of intermediate (hepatocyte-cholangiocyte) phenotype. J Hepatol. 2004;40(2):298–304.
8.
Tanaka S, Yamamoto T, Tanaka H, Kodai S, Ogawa M, Ichikawa T Hai S, Sakabe K, Uenishi T, Shuto T, et al. Potentiality of combined hepatocellular and intrahepatic cholangiocellular carcinoma originating from a hepatic precursor cell: Immunohistochemical evidence. Hepatol Res. 2005;32(1):52–7.CrossRefPubMed
9.
Shetty AS, Fowler KJ, Brunt EM, Agarwal S, Narra VR, Menias CO. Combined hepatocellular-cholangiocarcinoma: what the radiologist needs to know about biphenotypic liver carcinoma. Abdom Imaging. 2014;39(2):310–22.CrossRefPubMed
10.
Lee CH, Hsieh SY, Chang CJ, Lin YJ. Comparison of clinical characteristics of combined hepatocellular-cholangiocarcinoma and other primary liver cancers. J Gastroenterol Hepatol. 2013;28(1):122–7.CrossRefPubMed
11.
de Campos RO, Semelka RC, Azevedo RM, Ramalho M, Heredia V, Armao DM, Woosley JT. Combined hepatocellular carcinoma-cholangiocarcinoma: report of MR appearance in eleven patients. J Magn Reson Imaging. 2012;36(5):1139–47.
12.
Hwang J, Kim YK, Park MJ, Lee MH, Kim SH, Lee WJ, Rhim HC. Differentiating combined hepatocellular and cholangiocarcinoma from mass-forming intrahepatic cholangiocarcinoma using gadoxetic acid-enhanced MRI. J Magn Reson Imaging. 2012;36(4):881–9.
13.
Ebied O, Federle MP, Blachar A, Brancatelli G, Grazioli L, Cazals-Hatem D, Dondero F, Vilgrain V. Hepatocellular-cholangiocarcinoma: helical computed tomography findings in 30 patients. J Comput Assist Tomogr. 2003;27(2):117–24.
14.
Nishie A, Yoshimitsu K, Asayama Y, Irie H, Aibe H, Tajima T, Shinozaki K, Nakayama T, Kakihara D, Shimada M et al. Detection of combined hepatocellular and cholangiocarcinomas on enhanced CT: comparison with histologic findings. AJR Am J Roentgenol. 2005;184(4):1157–62.
15.
Fowler KJ, Sheybani A, Parker RR, Doherty S, M Brunt E, Chapman WC, Menias CO. Combined hepatocellular and cholangiocarcinoma (biphenotypic) tumors: imaging features and diagnostic accuracy of contrast-enhanced CT and MRI. AJR Am J Roentgenol. 2013;201(2):332–9.
16.
Kassahun WT, Hauss J. Management of combined hepatocellular and cholangiocarcinoma. Int J Clin Pract. 2008;62(8):1271–8.CrossRefPubMed
17.
Tang D, Nagano H, Nakamura M, Wada H, Marubashi S, Miyamoto A, Takeda Y, Umeshita K, Dono K, Monden M. Clinical and pathological features of Allen's type C classification of resected combined hepatocellular and cholangiocarcinoma: a comparative study with hepatocellular carcinoma and cholangiocellular carcinoma. J Gastrointest Surg. 2006;10(7):987–98.CrossRefPubMed
18.
Jarnagin WR, Weber S, Tickoo SK, Koea JB, Obiekwe S, Fong Y, DeMatteo RP, Blumgart LH, Klimstra D. Combined hepatocellular and cholangiocarcinoma: demographic, clinical, and prognostic factors. Cancer Am Cancer Soc. 2002;94(7):2040–6.
19.
Gibson JB. Histological typing of tumors of the liver, biliary tract, and pancreas. Geneva: World Health Organization; 1987.
20.
Theise N, Nakashima O, Park YN, Nakanuma Y. Combined hepatocellular-cholangiocarcinoma: WHO classification of tumours of the digestive system. Lyon, France: IARC; 2010. p. 225–7.
21.
Claudon M, Cosgrove D, Albrecht T, Bolondi L, Bosio M, Calliada F, Correas JM, Darge K, Dietrich C, D'Onofrio M et al. Guidelines and good clinical practice recommendations for contrast enhanced ultrasound (CEUS) - update 2008. Ultraschall Med. 2008;29(1):28–44.
22.
Claudon M, Dietrich CF, Choi BI, Cosgrove DO, Kudo M, Nolsoe CP, Piscaglia F, Wilson SR, Barr RG, Chammas MC et al. Guidelines and good clinical practice recommendations for contrast enhanced ultrasound (CEUS) in the liver--update 2012: a WFUMB-EFSUMB initiative in cooperation with representatives of AFSUMB, AIUM, ASUM, FLAUS and ICUS. Ultraschall Med. 2013;34(1):11–29.
23.
Boozari B, Soudah B, Rifai K, Schneidewind S, Vogel A, Hecker H, Hahn A, Schlue J, Dietrich CF, Bahr MJ et al. Grading of hypervascular hepatocellular carcinoma using late phase of contrast enhanced sonography - a prospective study. Dig Liver Dis. 2011;43(6):484–90.CrossRefPubMed
24.
Li R, Yuan MX, Ma KS, Li XW, Tang CL, Zhang XH, Guo DY, Yan XC. Detailed analysis of temporal features on contrast enhanced ultrasound may help differentiate intrahepatic cholangiocarcinoma from hepatocellular carcinoma in cirrhosis. Plos One. 2014;9(5):e98612.
25.
Kong WT, Wang WP, Huang BJ, Ding H, Mao F. Value of wash-in and wash-out time in the diagnosis between hepatocellular carcinoma and other hepatic nodules with similar vascular pattern on contrast-enhanced ultrasound. J Gastroenterol Hepatol. 2014;29(3):576–80.CrossRefPubMed
26.
Rimola J, Forner A, Reig M, Vilana R, de Lope CR, Ayuso C, Bruix J. Cholangiocarcinoma in cirrhosis: absence of contrast washout in delayed phases by magnetic resonance imaging avoids misdiagnosis of hepatocellular carcinoma. Hepatology. 2009;50(3):791–8.
27.
Iavarone M, Piscaglia F, Vavassori S, Galassi M, Sangiovanni A, Venerandi L, Forzenigo LV, Golfieri R, Bolondi L, Colombo M. Contrast enhanced CT-scan to diagnose intrahepatic cholangiocarcinoma in patients with cirrhosis. J Hepatol. 2013;58(6):1188–93.CrossRefPubMed
28.
29.
Yano Y, Yamamoto J, Kosuge T, Sakamoto Y, Yamasaki S, Shimada K, Ojima H, Sakamoto M Takayama T, Makuuchi M. Combined hepatocellular and cholangiocarcinoma: a clinicopathologic study of 26 resected cases. Jpn J Clin Oncol. 2003;33(6):283–7.CrossRefPubMed
30.
Ng IO, Shek TW, Nicholls J, Ma LT. Combined hepatocellular-cholangiocarcinoma: a clinicopathological study. J Gastroenterol Hepatol. 1998;13(1):34–40.CrossRefPubMed
31.
Taguchi J, Nakashima O, Tanaka M, Hisaka T, Takazawa T, Kojiro M. A clinicopathological study on combined hepatocellular and cholangiocarcinoma. J Gastroenterol Hepatol. 1996;11(8):758–64.CrossRefPubMed
32.
Liu CL, Fan ST, Lo CM, Ng IO, Lam CM, Poon RT, Wong J. Hepatic resection for combined hepatocellular and cholangiocarcinoma. Arch Surg. 2003;138(1):86–90.
33.
Lee CC, Wu CY, Chen JT, Chen GH. Comparing combined hepatocellular-cholangiocarcinoma and cholangiocarcinoma: a clinicopathological study. Hepatogastroenterology. 2002;49(48):1487–90.PubMed
34.
Yin X, Zhang BH, Qiu SJ, Ren ZG, Zhou J, Chen XH, Zhou Y, Fan J. Combined hepatocellular carcinoma and cholangiocarcinoma: clinical features, treatment modalities, and prognosis. Ann Surg Oncol. 2012;19(9):2869–76.
35.
Kim SA, Lee JM, Lee KB, Kim SH, Yoon SH, Han JK, Choi BI. Intrahepatic mass-forming cholangiocarcinomas: enhancement patterns at multiphasic CT, with special emphasis on arterial enhancement pattern--correlation with clinicopathologic findings. Radiology. 2011;260(1):148–57.
36.
Yu XH, Xu LB, Zeng H, Zhang R, Wang J, Liu C. Clinicopathological analysis of 14 patients with combined hepatocellular carcinoma and cholangiocarcinoma. Hepatobiliary Pancreat Dis Int. 2011;10(6):620–5.CrossRefPubMed
Metadata
Title
Combined hepatocellular carcinoma and cholangiocarcinoma (biphenotypic) tumors: clinical characteristics, imaging features of contrast-enhanced ultrasound and computed tomography
Authors
Rui Li
Dan Yang
Chun-Lin Tang
Ping Cai
Kuan-sheng Ma
Shi-Yi Ding
Xiao-Hang Zhang
De-Yu Guo
Xiao-Chu Yan
Publication date
01-12-2016
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2016
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-016-2156-x

Other articles of this Issue 1/2016

BMC Cancer 1/2016 Go to the issue

Research article

Identification of microRNA profile specific to cancer stem-like cells directly isolated from human larynx cancer specimens

Research article

Clinicopathological analysis in patients with neuroendocrine tumors that metastasized to the brain

Research article

Using gene expression from urine sediment to diagnose prostate cancer: development of a new multiplex mRNA urine test and validation of current biomarkers

Research article

The prognostic value of lactate dehydrogenase levels in colorectal cancer: a meta-analysis

Research article

CHEK2 represses breast stromal fibroblasts and their paracrine tumor-promoting effects through suppressing SDF-1 and IL-6

Technical advance

A cell transportation solution that preserves live circulating tumor cells in patient blood samples
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits