Skip to main content

Combined Hepatocellular-Cholangiocarcinoma

ICD-O code 8180/3

  • Reference work entry
  • First Online:
Tumors and Tumor-Like Lesions of the Hepatobiliary Tract
  • 158 Accesses

Abstract

Combined hepatocellular-cholangiocarcinoma (CHCC-C) is defined as a tumor that contains unequivocal, intimately mixed elements of both hepatocellular carcinoma and cholangiocarcinoma, resulting in a biphenotypic histologic picture. CHCC-C should not be confounded with collision tumors or rare hepatic mixed tumors. This is a rare liver malignancy of older individuals, probably accounting for less than 5 % of hepatic malignancies. The neoplasm develops in both non-cirrhotic and cirrhotic livers. Etiologic factors include hepatitis virus infections and alcoholic liver disease.

CHCC-C usually presents as a solitary tumor mass. Similar to hepatocellular carcinoma, the tumor tends to invade the portal vein system and bile ducts. Based on distinct histologic patterns, several types of CHCC-C are distinguished in the WHO classification, including a classical type and a type with stem cell features, the latter further subdivided into at least four subtypes. Rare variants of CHCC-C contain sarcomatoid components, or the HCC component is that of fibrolamellar hepatocellular carcinoma. CHCC-Cs are usually highly aggressive lesions with a high rate of metastatic spread.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 1,599.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 2,499.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Aishima S, Kuroda Y, Asayama Y, Taguchi K, Nishihara Y, Taketomi A, Tsuneyoshi M (2006) Prognostic impact of cholangiocellular and sarcomatous components in combined hepatocellular and cholangiocarcinoma. Hum Pathol 37:283–291

    Article  PubMed  Google Scholar 

  • Akiba J, Nakashima O, Hattori S, Tanikawa S, Takenaka M, Nakayama M, Kondo R, Nomura Y, Koura K et al (2013) Clinicopathologic analysis of combined hepatocellular-cholangiocarcinoma according to the latest WHO classification. Am J Surg Pathol 37:496–505

    Article  PubMed  Google Scholar 

  • Allen RA, Lisa JR (1949) Combined liver cell and bile duct carcinoma. Am J Pathol 25:647–655

    CAS  PubMed  PubMed Central  Google Scholar 

  • Amano H, Itamoto T, Emoto K, Hino H, Asahara T, Shimamoto F (2005) Granulocyte colony-stimulating factor-producing combined hepatocellular/ cholangiocellular carcinoma with sarcomatous change. J Gastroenterol 40:1158–1159

    Article  PubMed  Google Scholar 

  • Aoki K, Takayasu K, Kawano T, Muramatsu Y, Moriyama N, Wakao F, Yamamoto J et al (1993) Combined hepatocellular carcinoma and cholangiocarcinoma: clinical features and computed tomographic findings. Hepatology 18:1090–1095

    Article  CAS  PubMed  Google Scholar 

  • Ariizumi S, Kotera Y, Karagiri S, Nakano M, Yamamoto M (2012) Combined hepatocellular-cholangiocarcinoma had poor outcomes after hepatectomy regardless of Allen and Lisa class or the predominance of intrahepatic cholangiocarcinoma cells within the tumor. Ann Surg Oncol 19:1628–1636

    Article  PubMed  Google Scholar 

  • Asayama Y, Taguchi KK, Aishima SS, Nishi H, Matsuda K, Tsuneyoshi M (2002) The mode of tumour progression in combined hepatocellular carcinoma and cholangiocarcinoma: an immunohistochemical analysis of E-cadherin, alpha-catenin and beta-catenin. Liver 22:43–50

    Article  CAS  PubMed  Google Scholar 

  • Bedossa P (2007) Case 6: combined hepatocellular and cholangiocarcinoma (in French). Ann Pathol 27:112–114

    Article  PubMed  Google Scholar 

  • Bhagat V, Javle M, Agrawal A, Gibbs JF, Kuvshinoff B, Nava E, Iyer R (2006) Combined hepatocholangiocarcinoma: case-series and review of literature. Int J Gastrointest Cancer 37:27–34

    Article  PubMed  Google Scholar 

  • Bonne C (1937) Cancer and human races. Am J Cancer 30:435–454

    Article  Google Scholar 

  • Boonsakan P, Thangnapakorn O, Tapaneeyakorn J, Kositchaiwat S, Bunyaratvei S (2007) case report combined hepatocellular and cholangiocarcinoma with sarcomatous transformation. J Med Assoc Thai 90:574–580

    PubMed  Google Scholar 

  • Cabot J (1940) Case no. 26441. Primary cancer of the liver, combined type: adenocarcinoma and hepatoma. New Engl J Med 223:731–734

    Article  Google Scholar 

  • Cai X, Zhai J, Kalan DE, Zhang Y, Zhou L, Chen X, Qian G, Zhao Q, Li Y, Gao L et al (2012) background progenitor activation is associated with recurrence after hepatectomy of combined hepatocellular-cholangiocarcinoma. Hepatology 56:1804–1816

    Article  PubMed  PubMed Central  Google Scholar 

  • Cazals-Hatem D, Rebouissou S, Bioulac-Sage P, Bluteau O, Branché H, Franco D et al (2004) Clinical and molecular analysis of combined hepatocellular-cholangiocarcinomas. J Hepatol 41:292–298

    Article  CAS  PubMed  Google Scholar 

  • Chantajitr S, Wilasrusmee C, Lertsitichai P, Phromsopha N (2006) Combined hepatocellular and cholangiocarcinoma: clinical features and prognostic study in a Thai population. J Hepatobiliary Pancreat Surg 13:537–542

    Article  PubMed  Google Scholar 

  • Chi M, Mikhitarian K, Shi C, Goff LW (2012) Management of combined hepatocellular-cholangiocarcinoma: a case report and literature review. Gastrointest Cancer Res 5:199–202

    PubMed  PubMed Central  Google Scholar 

  • Choi BI, Han JK, Kim YI, Kim HC, Park JH, Kim CW, Han MC (1994) Combined hepatocellular and cholangiocarcinoma of the liver: sonography, CT, angiography, and iodized-oil CT with pathologic correlation. Abdom Imaging 19:43–46

    Article  CAS  PubMed  Google Scholar 

  • Chu KJ, Lu CD, Dong H, Fu XH, Zhang HW, Yao XP (2014) Hepatitis B virus-related combined hepatocellular-cholangiocarcinoma: clinicopathological and prognostic analysis of 390 cases. Eur J Gastroenterol Hepatol 26:192–199

    Article  CAS  PubMed  Google Scholar 

  • De Campos RO, Semelka RC, Azevedo RM, Ramalho M, Heredia V, Armao DM, Woosley JT (2012) Combined hepatocellular carcinoma-cholangiocarcinoma: report of MR appearance in eleven patients. J Magn Reson Imaging 36:1139–1147

    Article  PubMed  Google Scholar 

  • Deniz K, Torun E, Celikbilek M, Sözüer E (2011) Combined hepatocellular and cholangiocarcinoma associated with hepatolithiasis: report of a case. Surg Today 41:591–595

    Article  PubMed  Google Scholar 

  • Dusenbery D (1997) Combined hepatocellular-cholangiocarcinoma. Cytologic findings in four cases. Acta Cytol 41:903–909

    Article  CAS  PubMed  Google Scholar 

  • Ewing J (1940) Neoplastic diseases, 4th edn. W.B. Saunders Co., Philadelphia, p 740

    Google Scholar 

  • Fisher HP, Doppel W, Osborn M, Altmannsberger M (1988) Evidence for a hepatocellular lineage in a combined hepatocellular-cholangiocarcinoma of transitional type. Virchows Arch B Cell Pathol Incl Mol Pathol 56:71–76

    Article  CAS  PubMed  Google Scholar 

  • Fowler KJ, Sheybani A, Parker RA, Doherty S, Brunt M, Chapman WC, Menias CO (2013) Combined hepatocellular and cholangiocarcinoma (biphenotypic) tumors: imaging features and diagnostic accuracy of contrast-enhanced CT and MRI. AJR Am J Roentgenol 201:332–339

    Article  PubMed  Google Scholar 

  • Fujii H, Zhu XG, Matsumoto T, Inagaki M, Tokusashi Y, Miyokawa N, Fukusato T et al (2000) Genetic classification of combined hepatocellular-cholangiocarcinoma. Hum Pathol 31:1011–1017

    Article  CAS  PubMed  Google Scholar 

  • Fukukura Y, Taguchi J, Nakashima O, Wada Y, Kojiro M (1997) Combined hepatocellular and cholangiocarcinoma: correlation between CT findings and clinicopathologic features. J Comput Assist Tomogr 21:52–58

    Article  CAS  PubMed  Google Scholar 

  • Garancini M, Goffredo P, Pagni F, Romano F, Roman S, Sosa JA, Giardini V (2014) Combined hepatocellular-cholangiocarcinoma: a population-level analysis of an uncommon primary liver tumor. Liver Transpl 20:952–959

    Article  PubMed  Google Scholar 

  • Gibbons D, de las Morenas A (1997) Fine needle aspiration diagnosis of combined hepatocellular carcinoma and cholangiocarcinoma. A case report. Acta Cytol 41(suppl):1269–1272

    Article  CAS  PubMed  Google Scholar 

  • Goldzieher MA (1928) Über multiple Carcinome, ein Beitrag zur Frage der Histogenese des Lebercarcinoms. Virchows Arch Pathol Anat 267:326–338

    Article  Google Scholar 

  • Goodman ZD, Ishak KG, Langloss JM, Sesterhenn IA, Rabin L (1985) Combined hepatocellular-cholangiocarcinoma. A histologic and immunohistochemical study. Cancer 55:124–135

    Article  CAS  PubMed  Google Scholar 

  • Gustafsen E.G. (1937/38). An analysis of sixty-two cases of primary carcinoma of the liver based on 24’400 necropsies at Bellevue Hospital. Ann Int Med. 11:889–900

    Google Scholar 

  • Hanazaki K, Fujimori Y, Kajikawa S, Nakata S, Shimozawa N, Adachi W, Amano J (1998) Mixed hepatocellular carcinoma and cholangiocarcinoma treated by extended left hepatic lobectomy with resection of the right hepatic vein and preservation of the inferior right hepatic vein after hepatic arterial infusion chemotherapy. Hepatogastroenterology 45:812–815

    CAS  PubMed  Google Scholar 

  • Harada K, Terada T, Nakanuma Y, Furukawa Y, Kurumaya H (1993) A case of small combined hepatocellular and cholangiocellular carcinoma arising in a nodule of atypical adenomatous hyperplasia of the liver. Am J Gastroenterol 88:1968–1969

    CAS  PubMed  Google Scholar 

  • Haratake J, Hashimoto H (1995) An immunohistochemical analysis of 13 cases with combined hepatocellular and cholangiocellular carcinoma. Liver 15:9–15

    Article  CAS  PubMed  Google Scholar 

  • Hashimoto T, Nakamura H, Hori S, Tomoda K, Mitani T, Murakami T, Kozuka T, Monden M et al (1994) MR imaging of mixed hepatocellular and cholangiocellular carcinoma. Abdom Imaging 19:430–432

    Article  CAS  PubMed  Google Scholar 

  • Hauben E, Struyf N, Michielsen P, van Marck E (1996) Cytokeratin profiles and mucin secretion in combined hepatocellular-cholangiocarcinoma. A case report. Pathol Res Pract 192:488–491

    Article  CAS  PubMed  Google Scholar 

  • Hirohashi K, Uenishi T, Kubo S, Yamamoto T, Tanaka H, Shuto T, Kinoshita H (2002) The separate-lesion type combined hepatocellular carcinoma and cholangiocarcinoma. Hepatogastroenterology 49:806–809

    PubMed  Google Scholar 

  • Horie Y, Yamada M, Nakai K, Kawasaki H, Hirayama C, Matsui K, Kambe N, Shimao S (1989) Combined hepatocellular-cholangiocarcinoma associated with dermatomyositis. J Gastroenterol Hepatol 4:101–104

    Article  CAS  PubMed  Google Scholar 

  • Hunt JP, Varnholt H (2008) Mixed hepatocellular-cholangiocarcinoma may derive from “hepatogones”. Hepatobiliary Pancreat Dis Int 7:105

    PubMed  Google Scholar 

  • Hwang J, Kim YK, Park MJ, Lee MH, Kim SH, Lee WJ, Rhim HC (2012) Differentiating combined hepatocellular and cholangiocarcinoma from mass-forming intrahepatic cholangiocarcinoma using gadoxetic acid-enhanced MRI. J Magn Reson Imaging 36:881–889

    Article  PubMed  Google Scholar 

  • Ikeda H, Harada K, Sato Y, Sasaki M, Yoneda N, Kitamura S, Sudo Y, Ooi A, Nakanuma Y (2013) Clinicopathologic significance of combined hepatocellular-cholangiocarcinoma with stem cell subtype components with reference to the expression of putative stem cell markers. Am J Clin Pathol 140:329–340

    Article  PubMed  Google Scholar 

  • Imai Y, Oda H, Arai M, Shimizu S, Nakatsuru Y, Inoue T, Ishikawa T (1996) Mutational analysis of the p53 and K-ras genes and allelotype study of the Rb-1 gene for investigating the pathogenesis of combined hepatocellular-cholangiocellular carcinomas. Jpn J Cancer Res 87:1056–1062

    Article  CAS  PubMed  Google Scholar 

  • Jarnagin WR, Weber S, Tickoo SK, Koea JB, Objekwe S, Fong Y, DelMatteo RP, Blumgart LH, Klimstra D (2002) Combined hepatocellular and cholangiocarcinoma: demographic, clinical, and prognostic factors. Cancer 94:2040–2046

    Article  PubMed  Google Scholar 

  • Jeong BJ, Hyun DH, Lee KW, Ryu ST, Lee JW, Lee JI, Jeong S, Lee DH, Kim PS, Kim HH, Kim YS, Kim JM (2004) A case of sarcomatoid combined hepatocellular-cholangiocarcinoma (in Korean). Korean J Gastroenterol 43:56–60

    PubMed  Google Scholar 

  • Kakar S, Muir T, Murphy LM, Lloyd RV, Burgart LJ (2003) Immunoreactivity of Hep Par 1 in hepatic and extrahepatic tumors and its correlation with albumin in situ hybridization in hepatocellular carcinoma. Am J Clin Pathol 119:361–366

    Article  PubMed  Google Scholar 

  • Kanamoto M, Yoshizumi T, Ikegami T, Imura S, Morine Y, Ikemoto T, Sano N, Shimada M (2008) Cholangiolocellular carcinoma containing hepatocellular carcinoma and cholangiocellular carcinoma, extremely rare tumor of the liver: a case report. J Med Invest 55:161–165

    Article  PubMed  Google Scholar 

  • Kassahun WT, Hauss J (2008) Management of combined hepatocellular and cholangiocarcinoma. Int J Clin Pract 62:1271–1278

    Article  CAS  PubMed  Google Scholar 

  • Kilpatrick SE, Geisinger KR, Loggie BW, Hopkins MB (1993) Cytomorphology of combined hepatocellular-cholangiocarcinoma in fine needle aspirates of the liver. A report of two cases. Acta Cytol 37:943–947

    CAS  PubMed  Google Scholar 

  • Kim H, Park C, Han KH, Choi J, Kim YB, Kim JK, Park YN (2004a) Primary liver carcinoma of intermediate (hepatocyte-cholangiocyte) phenotype. J Hepatol 40:298–304

    Article  CAS  PubMed  Google Scholar 

  • Kim JH, Lee YG, Lee J, Jung CK, Kim HT, Kang H, Kho KH, Hong SP, Hwang SG et al (2004b) A case of combined hepatocellular-cholangiocarcinoma with sarcomatous transformation and second primary colon cancer (in Korean). Kor J Hepatol 10:142–147

    Google Scholar 

  • Kim KH, Lee SG, Park EH, Hwang S, Ahn CS, Moon DB, Ha TY, Song GW, Jung DH et al (2009) Surgical treatments and prognoses of patients with combined hepatocellular carcinoma and cholangiocarcinoma. Ann Surg Oncol 16:623–629

    Article  PubMed  Google Scholar 

  • Kim GM, Jeung HC, Kim D, Kim JH, Yoon SH, Jung ES, Shin SJ (2010a) A case of combined hepatocellular-cholangiocarcinoma with favorable response to systemic chemotherapy. Cancer Res Treat 42:235–238

    Article  PubMed  PubMed Central  Google Scholar 

  • Kim JH, Yoon HK, Ko GY, Gwon DI, Jang CS, Song HY, Shin JH, Sung KB (2010b) Nonresectable combined hepatocellular carcinoma and cholangiocarcinoma: analysis of the response and prognostic factors after transcatheter arterial chemoembolization. Radiology 255:270–277

    Article  PubMed  Google Scholar 

  • Kim GJ, Kim H, Park YN (2013) Increased expression of Yes-associated protein 1 in hepatocellular carcinoma with stemness and combined hepatocellular-cholangiocarcinoma. PLoS One 8:e75449

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kim SH, Park YN, Lim JH, Choi GH, Choi JS, Kim KS (2014) Characteristics of combined hepatocellular-cholangiocarcinoma and comparison with intrahepatic cholangiocarcinoma. Eur J Surg Oncol 40:976–981

    Article  CAS  PubMed  Google Scholar 

  • Kimoto T, Ugaki M (1982) Hepatocellular carcinoma combined with hepatic mesenchymal cell tumor and sarcoma. Acta Pathol Jpn 32:1131–1141

    CAS  PubMed  Google Scholar 

  • Koh KC, Lee H, Choi MS, Lee JH, Paik SW, Yoo BC, Rhee JC, Cho JW, Park CK, Kim HJ (2005) Clinicopathologic features and prognosis of combined hepatocellular cholangiocarcinoma. Am J Surg 189:120–125

    Article  PubMed  Google Scholar 

  • Kojiro M, Kawano Y, Kawasaki H, Nakashima T, Ikezaki H (1982) Thorotrast-induced hepatic angiosarcoma, and combined hepatocellular and cholangiocarcinoma in a single patient. Cancer 49:2161–2164

    Article  CAS  PubMed  Google Scholar 

  • Kondo Y, Nakajima T (1987) Pseudoglandular hepatocellular carcinoma. A morphogenetic study. Cancer 60:1032–1037

    Article  CAS  PubMed  Google Scholar 

  • Koster H, Kasman LP (1932) Primary duplex liver carcinoma. Am J Surg 17:237–241

    Article  Google Scholar 

  • Kwon Y, Lee SK, Kim JS, Ro JY, Yu E (2002) Synchronous hepatocellular carcinoma and cholangiocarcinoma arising in two different dysplastic nodules. Mod Pathol 15:1096–1101

    Article  PubMed  Google Scholar 

  • L’Esperance E (1915) Atypical hemorrhagic malignant hepatoma. J Med Res 32:225–249

    PubMed  PubMed Central  Google Scholar 

  • Larson CP (1937) Multiple liver-cell carcinoma (primary type). Report of a case. Northwest Med 36:388–391

    Google Scholar 

  • Lee CC, Wu CY, Chen JT, Chen GH (2002) Comparing combined hepatocellular-cholangiocarcinoma and cholangiocarcinoma: a clinicopathologic study. Hepatogastroenterology 49:1487–1490

    PubMed  Google Scholar 

  • Lee WS, Lee KW, Heo JS, Kim SJ, Choi SH, Kim YI, Joh JW (2006) Comparison of combined hepatocellular and cholangiocarcinoma with hepatocellular carcinoma and intrahepatic cholangiocarcinoma. Surg Today 36:892–897

    Article  PubMed  Google Scholar 

  • Lee JH, Chung GE, Yu SJ, Hwang SY, Kim JS, Kim HY, Yoon JH, Lee HS, Yi NJ et al (2011) Long-term prognosis of combined hepatocellular and cholangiocarcinoma after curative resection comparison with hepatocellular carcinoma and cholangiocarcinoma. J Clin Gastroenterol 45:69–75

    PubMed  Google Scholar 

  • Lee CH, Hsieh SY, Chang CJ, Lin YJ (2013) Comparison of clinical characteristics of combined hepatocellular-cholangiocarcinoma and other primary liver cancers. J Gastroenterol Hepatol 28:122–127

    Article  PubMed  Google Scholar 

  • Leong AS, Sormunen RT, Tasui WM, Liew CT (1998) Hep Par 1 and selected antibodies in the immunohistological distinction of hepatocellular carcinoma from cholangiocarcinoma, combined tumours and metastatic carcinoma. Histopathology 33:318–324

    Article  CAS  PubMed  Google Scholar 

  • Li X, Jiang W, Feng T, Wang Z (2012) Concurrent occurrence of primary hepatocellular and cholangiocellular carcinoma in the different part of the liver: a case report. Int J Clin Exp Med 5:355–357

    PubMed  PubMed Central  Google Scholar 

  • Libbrecht L (2006) Hepatic progenitor cells in human liver tumor development. World J Gastroenterol 12:6261–6265

    Article  PubMed  PubMed Central  Google Scholar 

  • Lin G, Toh CH, Wu RC, Ko SF, Ng SH, Chou WC, Tseng JH (2008) Combined hepatocellular and cholangiocarcinoma: prognostic factors investigated by computed tomography/magnetic resonance imaging. Int J Clin Pract 62:1199–1205

    Article  CAS  PubMed  Google Scholar 

  • Maarouf A, Adham M, Scoazec JY, Partensky C (2008) Mixed hepato/cholangiocarcinoma with paraneoplastic hypercalcemia. J Hepatobiliary Pancreat Surg 15:224–227

    Article  PubMed  Google Scholar 

  • Maeda T, Adachi E, Kajiyama K, Sugimachi K, Tsuneyoshi M (1995) Combined hepatocellular and cholangiocarcinoma: proposed criteria according to cytokeratin expression and analysis of clinicopathologic features. Hum Pathol 26:956–964

    Article  CAS  PubMed  Google Scholar 

  • Maeda A, Ebata T, Matsunaga K, Kanemoto H, Bando E, Yamaguchi S, Furukawa H, Uesaka K (2005) Primary liver cancer with bidirectional differentiation into hepatocytes and biliary epithelium. J Hepatobiliary Pancreat Surg 12:484–487

    Article  PubMed  Google Scholar 

  • Matsumoto M, Wakiyama S, Shiba H, Gocho T, Misawa T, Ishida Y, Itsubo M, Suzuki M, Yanaga K (2014) Combined hepatocellular-cholangiocarcinoma producing parathyroid hormone-related protein: report of a case. Surg Today 44:1577–1583

    Article  PubMed  Google Scholar 

  • Moon VH (1929) Primary carcinoma of liver with metastasis to bone. Arch Path 8:938–943

    Google Scholar 

  • Morita D, Kagata Y, Ogata S, Tsuda H, Hatsuse K, Mochizuki H, Matsubara O (2006) Combined hepatocellular carcinoma and cholangiocarcinoma with components of mucinous carcinoma arising in a cirrhotic liver. Pathol Int 56:222–226

    Article  PubMed  Google Scholar 

  • Murakami T, Yano H, Maruiwa M, Sugihara S, Kojiro M (1987) Establishment and characterization of a human combined hepatocholangiocarcinoma cell line and its heterologous transplantation in nude mice. Hepatology 7:551–556

    Article  CAS  PubMed  Google Scholar 

  • Murata M, Miyoshi Y, Iwao K, Wada H, Shibata K, Tateishi H, Shimano T, Ohasawa M et al (2001) Combined hepatocellular/cholangiocellular carcinoma with sarcomatoid features: genetic analysis for histogenesis. Hepatol Res 21:220–227

    Article  PubMed  Google Scholar 

  • Nakajima T, Kubosawa H, Kondo Y, Konno A, Iwama S (1988) Combined hepatocellular-cholangiocarcinoma with variable sarcomatous transformation. Am J Clin Pathol 90:309–312

    Article  CAS  PubMed  Google Scholar 

  • Nakamura S, Suzuki S, Sakaguchi T, Serizawa A, Konno H, Baba S, Baba S, Muro H (1996) Surgical treatment of patients with mixed hepatocellular carcinoma and cholangiocarcinoma. Cancer 78:1671–1676

    Article  CAS  PubMed  Google Scholar 

  • Nakasho K, Yamanaka N, Okamoto E (1996) A case of combined or mixed hepatocellular and cholangiocarcinoma with sarcomatous components – immunohistochemical characteristics and histogenesis (in Japanese). Nihon Shokakibyo Gakkai Zasshi 93:206–211

    CAS  PubMed  Google Scholar 

  • Neumann MA (1944) Primary carcinoma of the liver with metastases to bone. Am J Pathol 20:895–909

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ng IO, Shek TW, Nicholls J, Ma LT (1998) Combined hepatocellular-cholangiocarcinoma: a clinicopathological study. J Gastroenterol Hepatol 13:34–40

    Article  CAS  PubMed  Google Scholar 

  • Nishie A, Yoshimitsu K, Asayama Y, Irie H, Aibe H, Tajima T, Shinozaki K, Nakayama T et al (2005) Detection of combined hepatocellular and cholangiocarcinomas on enhanced CT: comparison with histologic findings. AJR Am J Roentgenol 184:1157–1162

    Article  PubMed  Google Scholar 

  • O’Connor K, Walsh JC, Schaeffer DF (2014) Combined hepatocellular-cholangiocarcinoma (cHCC-CC): a distinct entity. Ann Hepatol 13:317–322

    PubMed  Google Scholar 

  • Okada Y, Jinno K, Moriwaki S, Morichika S, Torigoe S, Arima T, Nagashima H, Koprowski H (1987) Expression of ABH and Lewis blood group antigens in combined hepatocellular –cholangiocarcinoma. Possible evidence for the hepatocellular origin of combined hepatocellular-cholangiocarcinoma. Cancer 60:345–352

    Article  CAS  PubMed  Google Scholar 

  • Omagari K, Makiyama K, Ikuno N (1995) Combined hepatocellular and cholangiocarcinoma (in Japanese). Ryoikibetsu Shokogun Shirizu 7:473–475

    PubMed  Google Scholar 

  • Panjala C, Senecal DL, Bridges MD, Kim GP, Nakleh RE, Nguyen JH, Harnois DM (2010) The diagnostic conundrum and liver transplantation outcome for combined hepatocellular-cholangiocarcinoma. Am J Transplant 10:1263–1267

    Article  CAS  PubMed  Google Scholar 

  • Papotti M, Sambataro D, Marchesa P, Negro F (1997) A combined hepatocellular/cholangiocellular carcinoma with sarcomatoid features. Liver 17:47–52

    Article  CAS  PubMed  Google Scholar 

  • Park H, Choi KH, Choi SB, Choi JW, Kim do Y, Ahn SH, Kim KS, Choi JS, Han KH, Chon CY, Park JY (2011a) Clinicopathological characteristics in combined hepatocellular-cholangiocarcinoma: a single center study in Korea. Yonsei Med J 52:753–760

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Park HS, Bae JS, Jang KY, Lee JH, Yu HC, Jung JH, Cho BH, Chung MJ, Moon WS (2011b) Clinicopathologic study on combined hepatocellular carcinoma and cholangiocarcinoma: with emphasis on the intermediate cell morphology. J Korean Med Sci 26:1023–1030

    Article  PubMed  PubMed Central  Google Scholar 

  • Pérez-Roldan F, Carretero L, Aguirre A, Banares R, Casado M, Cos E, Clemente G (1995) Hepato-cholangiocarcinoma with diffuse metastases and hypercalcemia (in Spanish). Rev Esp Enferm Dig 87:743–747

    PubMed  Google Scholar 

  • Phongkikarun S, Srisuwan T, Sornmayura P, Jatchavala J (2007) Combined hepatocellular and cholangiocarcinoma: CT findings with emphasis on multiphasic helical CT. J Med Assoc Thai 90:113–120

    Google Scholar 

  • Portolani N, Baiocchi GL, Coniglio A, Piardi T, Grazioli L, Benetti A, Ferrari Bravo A, Giulini SM (2008) Intrahepatic cholangiocarcinoma and combined hepatocellular-cholangiocarcinoma: a Western experience. Ann Surg Oncol 15:1880–1890

    Article  PubMed  Google Scholar 

  • Prescott WH (1895) Seven cases of primary carcinoma of the liver. Med Surg Rep Boston City Hosp 6:245–267

    Google Scholar 

  • Pua U, Low SC, Tan YM, Lim KH (2009) Combined hepatocellular and cholangiocarcinoma with sarcomatoid transformation: radiologic-pathologic correlation of a case. Hepatol Int 3:587–592

    Article  PubMed  PubMed Central  Google Scholar 

  • Rasario GM (1934) Adeno-carcinoma epatocellulare primitive del fegato. Riv di Clin Med 35:767–786

    Google Scholar 

  • Rasario GM (1937) Ulteriore contributo allo studio clinico ed anatomo-patologico della cancro-cirrosi del fegato. Clin Med Ital 68:807–817

    Google Scholar 

  • Robrechts C, De Vos R, Van den Heuvel M, Van Cutsem F, Van Damme B, Desmet V, Roskams T (1998) Primary liver tumour of intermediate (hepatocyte-bile duct cell) phenotype: a progenitor cell tumour? Liver 18:288–293

    Article  CAS  PubMed  Google Scholar 

  • Rosa M, Mohammadi A (2014) Cytologic features of fibrolamellar carcinoma with mucin production: a rare variant of combined hepatocellular-cholangiocarcinoma. Diagn Cytopathol 42:431–435

    Article  PubMed  Google Scholar 

  • Saboo SS, Krajewski KM, Jagannathan JP, O’Regan KN, Odze R, Ramaiya N, Wolpin BM (2011) Rapid progression of combined hepatocellular carcinoma and cholangiocarcinoma. Cancer Imaging 11:37–41

    Article  PubMed  PubMed Central  Google Scholar 

  • Saito M, Hige S, Takeda H, Tomaru U, Shibata M, Asaka M (2001) Combined hepatocellular carcinoma and cholangiocarcinoma growing into the common bile duct. J Gastroenterol 36:842–847

    Article  CAS  PubMed  Google Scholar 

  • Sanada Y, Shiozaki S, Aoki H, Takakura N, Yoshida K, Yamaguchi Y (2005) A clinical study of 11 cases of combined hepatocellular-cholangiocarcinoma. Assessment of enhancement patterns on dynamics computed tomography before resection. Hepatol Res 32:185–195

    Article  PubMed  Google Scholar 

  • Sapisochin G, Fidelman N, Roberts JP, Yao FY (2011) Mixed hepatocellular cholangiocarcinoma and intrahepatic cholangiocarcinoma in patients undergoing transplantation for hepatocellular carcinoma. Liver Transpl 17:934–942

    Article  PubMed  Google Scholar 

  • Sasaki M, Nakanuma Y, Ho SB, Kim YS (1998) Cholangiocarcinomas arising in cirrhosis and combined hepatocellular-cholangiocellular carcinomas share apomucin profiles. Am J Clin Pathol 109:302–308

    Article  CAS  PubMed  Google Scholar 

  • Sasaki A, Kawano K, Aramaki M, Ohno T, Tahara K, Takeuchi Y, Yoshida T, Kitano S (2001) Clinicopathologic study of mixed hepatocellular and cholangiocellular carcinoma: modes of spreading and choice of surgical treatment by reference to macroscopic type. J Surg Oncol 76:37–46

    Article  CAS  PubMed  Google Scholar 

  • Sasaki M, Sato H, Kakuda Y, Sato Y, Choi JH, Nakanuma Y (2014) Clinicopathological significance of ‘subtypes with stem-cell feature’ in combined hepatocellular-cholangiocarcinoma. Liver Int. doi:10.1111/liv.12563

    PubMed Central  Google Scholar 

  • Shetty AS, Fowler KJ, Brunt EM, Agarwal S, Narra VR, Menias CO (2014) Combined hepatocellular-cholangiocarcinoma: what the radiologist needs to know about biphenotypic liver carcinoma. Abdom Imaging 39:310–322

    Article  PubMed  Google Scholar 

  • Shin CI, Lee JM, Kim SH, Choi JY, Lee JY, Han JK, Jo SY, Choi BI (2007) Recurrence patterns of combined hepatocellular-cholangiocarcinoma on enhanced computed tomography. J Comput Assist Tomogr 31:109–115

    Article  PubMed  Google Scholar 

  • Shiomi S, Sasaki N, Kawashima D, Jomura H, Fukuda T, Kuroki T, Koyama K, Kawabe J et al (1999) Combined hepatocellular carcinoma and cholangiocarcinoma with high F-18 fluorodeoxyglucose positron emission tomographic uptake. Clin Nucl Med 24:370–371

    Article  CAS  PubMed  Google Scholar 

  • Shiraishi M, Takushi Y, Simoji H, Oshiro T, Shinzato S, Tanigawa N, Kusano T, Muto Y (1998) Combined hepatocellular and cholangiocellular carcinoma in a non-cirrhotic liver. J Gastroenterol 33:593–596

    Article  CAS  PubMed  Google Scholar 

  • Shirakawa H, Kuronuma T, Nishimura Y, Hasebe T, Nakano M, Gotohda N, Takahashi S et al (2009) Glypican-3 is a useful diagnostic marker for a component of hepatocellular carcinoma in human liver cancer. Int J Oncol 34:649–656

    CAS  PubMed  Google Scholar 

  • Singh S, Chakraborty S, Bonthus N, Radio S, Hussain SM, Sasson A (2013) Combined hepatocellular cholangiocarcinoma: a case report and review of literature. Dig Dis Sci 58:2114–2123

    Article  PubMed  Google Scholar 

  • Sonobe H, Hayashi K, Takahashi K, Ohtsuki Y, Matsumoto K, Ohnishi S, Jinno K (1987) Combined hepatocellular and cholangiocarcinoma arising in a cirrhotic liver. Report of an autopsy case. Acta Pathol Jpn 37:1945–1952

    CAS  PubMed  Google Scholar 

  • Sugihara S, Nakahara T, Maruiwa M, Kojiro M, Iwai I, Tanaka M, Hirai K, Majima Y et al (1987) An autopsy case with a combination of hepatocellular carcinoma and cholangiocellular carcinoma (in Japanese). Gan No Rinsho 33:205–210

    CAS  PubMed  Google Scholar 

  • Taguchi J, Nakashima O, Tanaka M, Hisaka T, Takazawa T, Kojiro M (1996) A clinicopathological study on combined hepatocellular and cholangiocarcinoma. J Gastroenterol Hepatol 11:758–764

    Article  CAS  PubMed  Google Scholar 

  • Tanaka T, Imamura A, Hayashi S, Tsuruta K, Igari T, Koike M, Tanaka S (1998) Minute mixed hepatoma with two components: hepatocellular and cholangiocarcinoma which developed on liver cirrhosis with HCV. Hepatogastroenterology 45:220–223

    CAS  PubMed  Google Scholar 

  • Tanaka S, Hirohashi K, Uenishi T, Yamamoto T, Hamba H, Kubo S, Tanaka H, Shuto T et al (2004) A mixed hepatocellular carcinoma and cholangiocarcinoma: dual expression of biliary-type cytokeratin and hepatocyte specific marker. Hepatogastroenterology 51:839–841

    PubMed  Google Scholar 

  • Tanaka K, Honna T, Kitano Y, Kuroda T, Tanaka K, Morikawa N, Matsuda H, Kawashima N et al (2005a) Combined fibrolamellar carcinoma and cholangiocarcinoma exhibiting biphenotypic antigen expression: a case report. J Clin Pathol 58:884–887

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tanaka S, Yamamoto T, Tanaka H, Kodai S, Ogawa M, Ichikawa T, Hai S, Sakabe K et al (2005b) Potentiality of combined hepatocellular and intrahepatic cholangiocellular carcinoma originating from a hepatic precursor cell: immunohistochemical evidence. Hepatol Res 32:52–57

    Article  CAS  PubMed  Google Scholar 

  • Tang D, Nagano H, Nakamura M, Wada H, Marubashi S, Miyamoto A, Takeda Y, Umeshita K et al (2006) 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. Gastrointest Surg 10:987–998

    Article  Google Scholar 

  • Terada T (2013) Combined hepatocellular-cholangiocarcinoma with stem cell features, ductal plate malformation subtype: a case report and proposal of a new subtype. Int J Clin Exp Pathol 6:737–748

    PubMed  PubMed Central  Google Scholar 

  • Theise ND, Yao JL, Harada K, Hytiroglou P, Portmann B, Thung SN, Tsui W, Ohta H, Nakanuma Y (2003) Hepatic ‘stem cell’ malignancies in adults: four cases. Histopathology 43:263–271

    Article  CAS  PubMed  Google Scholar 

  • Theise ND, Nakashima O, Park YN, Nakanuma Y (2010) Combined hepatocellular-cholangiocarcinoma. WHO classification of tumours of the digestive system, 4th edn. IARC, Lyon, pp 225–227

    Google Scholar 

  • Tickoo SK, Zee SY, Obiekwe S, Xiao H, Koea J, Robiou C, Blumgart LH, Jarnagin W et al (2002) Combined hepatocellular-cholangiocarcinoma. A histopathologic, immunohistochemical, and in situ hybridization study. Am J Surg Pathol 26:989–997

    Article  PubMed  Google Scholar 

  • Toh CH, Cheung YC, Ng SH, Lin CY, Chan SC, Ng KK (2004) Combined hepatocellular-cholangiocarcinoma: a case report. Int J Clin Pract 58:1170–1173

    Article  CAS  PubMed  Google Scholar 

  • Tomimatsu M, Ishiguro N, Taniai M, Okuda H, Saito A, Obata H, Yamamoto M, Takasaki K et al (1993) Hepatitis C virus antibody in patients with primary liver cancer (hepatocellular carcinoma, cholangiocarcinoma, and combined hepatocellular-cholangiocarcinoma) in Japan. Cancer 72:683–688

    Article  CAS  PubMed  Google Scholar 

  • Tramontano V, Fittipaldi C (1930) Sui cosidetti tumori a cellule giganti. Tumori 16:501–518

    Google Scholar 

  • Tsuneyama K, Kaizaki Y, Doden K, Kidani E, Harada K, Sasaki M, Nakanuma Y (2003) Combined hepatocellular and cholangiocarcinoma with marked squamous cell carcinoma components arising in non-cirrhotic liver. Pathol Int 53:90–97

    Article  PubMed  Google Scholar 

  • Uenishi T, Hirohashi K, Shuto T, Yamamoto T, Kubo S, Tanaka H, Ikebe T, Kinoshita H (2000) Surgery for mixed hepatocellular and cholangiocellular carcinoma. Hepatogastroenterology 47:832–834

    CAS  PubMed  Google Scholar 

  • Uenishi T, Hirohashi K, Shuto T, Tsukamoto T, Yamamoto T, Ogawa M, Kubo S, Tanaka H et al (2002) Primary liver cancer with dual expression of hepatocyte and bile duct epithelial markers. Hepatogastroenterology 49:1092–1094

    PubMed  Google Scholar 

  • Utsunomiya T, Saitsu H, Saku M, Takeshita M, Yoshida K, Kajiyama K, Sugimachi K (2000) A resected case of combined hepatocellular carcinoma and cholangiocarcinoma associated with cystic formation. Hepatogastroenterology 47:851–854

    CAS  PubMed  Google Scholar 

  • Van Eyken P, Sciot R, Brrock P, Casteels-Van Daele M, Ramaekers FCS, Desmet VJ (1990) Abundant expression of cytokeratin 7 in fibrolamellar carcinoma of the liver. Histopathology 17:101–107

    Article  PubMed  Google Scholar 

  • Varnholt H, Asayama Y, Aishima S, Taguchi K, Sugimachi K, Tsuneyoshi M (2002) C-met and hepatocyte growth factor expression in combined hepatocellular and cholangiocarcinoma. Oncol Rep 9:35–41

    CAS  PubMed  Google Scholar 

  • Wachtel MS, Zhang Y, Xu T, Chiriva-Internati M, Frezza EE (2008) Combined hepatocellular cholangiocarcinomas; analysis of a large database. Clin Med Pathol 1:43–47

    PubMed  PubMed Central  Google Scholar 

  • Wada K, Kondo F, Kubosawa H, Kondo Y (1986) Combined hepatocellular and mucinous carcinoma. Acta Pathol Jpn 36:285–291

    CAS  PubMed  Google Scholar 

  • Wakasa T, Wakasa K, Shutou T, Hai S, Kubo S, Hirohashi K, Umshita K, Monden M (2007) A histopathological study on combined hepatocellular and cholangiocarcinoma: cholangiocarcinoma component is originated from hepatocellular carcinoma. Hepatogastroenterology 54:508–513

    PubMed  Google Scholar 

  • Wang J, Wang F, Kessinger A (2010) Outcome of combined hepatocellular and cholangiocarcinoma of the liver. J Oncol 2010 pii:917356. doi:10.1155/2010/917356

    Google Scholar 

  • Ward SC, Huang J, Tickoo SK, Thung SN, Ladanyi M, Klimstra DS (2010) Fibrolamellar carcinoma of the liver exhibits immunohistochemical evidence of both hepatocyte and bile duct differentiation. Mod Pathol 23:1180–1190

    Article  CAS  PubMed  Google Scholar 

  • Warvi WN (1944) Primary neoplasms of the liver. Arch Pathol 37:367–382

    Google Scholar 

  • Wee A, Nilsson B (1999) Combined hepatocellular-cholangiocarcinoma. Diagnostic challenge in hepatic fine needle aspiration biopsy. Acta Cytol 43:131–138

    Article  CAS  PubMed  Google Scholar 

  • Wells HG (1903) Primary carcinoma of the liver. Am J Med Sci 126:403–417

    Article  Google Scholar 

  • Willekens I, Hoorens A, Geers C, Op de beeck B, Vandenbroucke F, de mey J (2009) Combined hepatocellular and cholangiocellular carcinoma presenting with radiological characteristics of focal nodular hyperplasia. World J Gastroenterol 15:3940–3943

    Article  PubMed  PubMed Central  Google Scholar 

  • Wu PC, Fang JW, Lau VK, Lai CL, Lo CK, Lau JY (1996) Classification of hepatocellular carcinoma according to hepatocellular and biliary differentiation markers. Clinical and biological implications. Am J Pathol 149:1167–1175

    CAS  PubMed  PubMed Central  Google Scholar 

  • Yano H, Iemura A, Haramaki M, Momosaki S, Ogasawara S, Higaki K, Kojiro M (1996) A human combined hepatocellular and cholangiocarcinoma cell line (KMCH-2) that shows the features of hepatocellular carcinoma or cholangiocarcinoma under different growth conditions. J Hepatol 24:413–422

    Article  CAS  PubMed  Google Scholar 

  • Yano Y, Yamamoto J, Kosuge T, Sakamoto Y, Yamasaki S, Shimada K, Ojima H et al (2003) Combined hepatocellular and cholangiocarcinoma: a clinicopathologic study of 26 resected cases. Jpn J Clin Oncol 33:283–287

    Article  PubMed  Google Scholar 

  • Yarze JC, Herlihy KJ, Scalia SV (2005) Cholangiohepatoma presenting with recurrent cholangitis. Dig Dis Sci 50:552–553

    Article  PubMed  Google Scholar 

  • Yeh MM (2010) Pathology of combined hepatocellular-cholangiocarcinoma. J Gastroenterol Hepatol 25:1485–1492

    Article  PubMed  Google Scholar 

  • Yoshida T, Okazaki N, Yoshino M, Moriyama N, Hirohashi S (1985) A case of diffuse type of combined hepatocellular and cholangiocellular carcinoma initially presenting as a localized small nodule. Jpn J Cancer Res 76:1186–1192

    CAS  PubMed  Google Scholar 

  • Zhan Q, Shen BY, Deng XX, Zhu ZC, Chen H, Peng CH, Li HW (2012) Clinical and pathological analysis of 27 patients with combined hepatocellular-cholangiocarcinoma in an Asian center. J Hepatobiliary Pancreat Sci 19:361–369

    Article  PubMed  Google Scholar 

  • Zhang F, Chen XP, Zhang W, Dong HH, Xiang S, Zhang WG, Zhang BX (2008) Combined hepatocellular cholangiocarcinoma originating from hepatic progenitor cells: immunohistochemical and double-fluorescence immunostaining evidence. Histopathology 52:224–232

    Article  CAS  PubMed  Google Scholar 

  • Zhou YM, Yang JM, Wang B, Xu F, Tong Y, Li DQ (2007) Combined hepatocellular carcinoma and cholangiocarcinoma: a case report and review of the literature. Hepatobiliary Pancreat Dis Int 6:656–659

    PubMed  Google Scholar 

  • Zhou YM, Zhang XF, Wu LP, Sui CJ, Yang JM (2014) Risk factors for combined hepatocellular-cholangiocarcinoma: a hospital-based case-control study. World J Gastroenterol 20:12615–12620

    Article  PubMed  PubMed Central  Google Scholar 

  • Zuo HQ, Yan LN, Zeng Y, Yang JY, Luo HZ, Liu JW, Zhou LX (2007) Clinicopathological characteristics of 15 patients with combined hepatocellular carcinoma and cholangiocarcinoma. Hepatobiliary Pancreat Dis Int 6:161–165

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Arthur Zimmermann .

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer International Publishing Switzerland

About this entry

Cite this entry

Zimmermann, A. (2017). Combined Hepatocellular-Cholangiocarcinoma. In: Tumors and Tumor-Like Lesions of the Hepatobiliary Tract. Springer, Cham. https://doi.org/10.1007/978-3-319-26956-6_26

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-26956-6_26

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-26954-2

  • Online ISBN: 978-3-319-26956-6

  • eBook Packages: MedicineReference Module Medicine

Publish with us

Policies and ethics