Skip to main content
SpringerLink
Log in

Cholangiocarcinoma

  • Chapter
Surgical Pathology of Liver Tumors

Abstract

Cholangiocarcinomas are not homogeneous tumors, but show a variety of growth patterns both grossly and microscopically. These various patterns are important to recognize for diagnosis and prognosis and are illustrated and discussed in this chapter. Subtypes of cholangiocarcinoma are also important to recognize and are illustrated and reviewed.

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

Access this chapter

Log in via an institution
eBook
USD 16.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
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

  1. Edge SB, American Joint Committee on Cancer, American Cancer Society. AJCC cancer staging handbook: from the AJCC cancer staging manual. 7th ed. New York: Springer; 2010. p. 718, xix.

    Google Scholar 

  2. Rizvi S, Gores GJ. Pathogenesis, diagnosis, and management of cholangiocarcinoma. Gastroenterology. 2013;145:1215–29.

    CAS  PubMed  Google Scholar 

  3. Khan SA, Toledano MB, Taylor-Robinson SD. Epidemiology, risk factors, and pathogenesis of cholangiocarcinoma. HPB (Oxford). 2008;10:77–82.

    CAS  Google Scholar 

  4. Shaib Y, El-Serag HB. The epidemiology of cholangiocarcinoma. Semin Liver Dis. 2004;24:115–25.

    PubMed  Google Scholar 

  5. Chaiteerakij R, Yang JD, Harmsen WS, Slettedahl SW, Mettler TA, Fredericksen ZS, et al. Risk factors for intrahepatic cholangiocarcinoma: association between metformin use and reduced cancer risk. Hepatology. 2013;57:648–55.

    PubMed Central  CAS  PubMed  Google Scholar 

  6. Sempoux C, Jibara G, Ward SC, Fan C, Qin L, Roayaie S, et al. Intrahepatic cholangiocarcinoma: new insights in pathology. Semin Liver Dis. 2011;31:49–60.

    PubMed  Google Scholar 

  7. Craig JR, Peters RL, Edmondson HA. Tumors of the liver and intrahepatic bile ducts. Atlas of tumor pathology. Washington, DC: Armed Forces Institute of Pathology; 1989. p. 280. Supt. of Docs., U.S. G.P.O. For sale by the Armed Forces Institute of Pathology.

    Google Scholar 

  8. Yamamoto M, Takasaki K, Nakano M, Takasaki K, Nakano M, Saito A. Minute nodular intrahepatic cholangiocarcinoma. Cancer. 1998;82:2145–9.

    CAS  PubMed  Google Scholar 

  9. Kobayashi M, Ikeda K, Saitoh S, Suzuki F, Tsubota A, Suzuki Y, et al. Incidence of primary cholangiocellular carcinoma of the liver in Japanese patients with hepatitis C virus-related cirrhosis. Cancer. 2000;88:2471–7.

    CAS  PubMed  Google Scholar 

  10. El-Serag HB, Engels EA, Landgren O, Chiao E, Henderson L, Amaratunge HC, et al. Risk of hepatobiliary and pancreatic cancers after hepatitis c virus infection: a population-based study of U.S. veterans. Hepatology. 2009;49:116–23.

    PubMed Central  PubMed  Google Scholar 

  11. Akisawa N, Maeda T, Tsuda K, Nishimori I, Morita M, Iwasaki S, et al. Primary biliary cirrhosis associated with cholangiocarcinoma. Dig Dis Sci. 1998;43:2138–42.

    CAS  PubMed  Google Scholar 

  12. Bergquist A, Glaumann H, Persson B, Broomé U. Risk factors and clinical presentation of hepatobiliary carcinoma in patients with primary sclerosing cholangitis: a case-control study. Hepatology. 1998;27:311–6.

    CAS  PubMed  Google Scholar 

  13. Altaee MY, Johnson PJ, Farrant JM, Williams R. Etiologic and clinical characteristics of peripheral and hilar cholangiocarcinoma. Cancer. 1991;68:2051–5.

    CAS  PubMed  Google Scholar 

  14. Shin HR, Oh JK, Masuyer E, Curado MP, Bouvard V, Fang YY, et al. Epidemiology of cholangiocarcinoma: an update focusing on risk factors. Cancer Sci. 2010;101:579–85.

    CAS  PubMed  Google Scholar 

  15. Bouvard V, Baan R, Straif K, Grosse Y, Secretan B, El Ghissassi F, et al. A review of human carcinogens–part b: biological agents. Lancet Oncol. 2009;10:321–2.

    PubMed  Google Scholar 

  16. Tsui WM, Chan YK, Wong CT, Lo YF, Yeung YW, Lee YW. Hepatolithiasis and the syndrome of recurrent pyogenic cholangitis: clinical, radiologic, and pathologic features. Semin Liver Dis. 2011;31:33–48.

    PubMed  Google Scholar 

  17. Blechacz B, Komuta M, Roskams T, Gores GJ. Clinical diagnosis and staging of cholangiocarcinoma. Nat Rev Gastroenterol Hepatol. 2011;8:512–22.

    PubMed Central  PubMed  Google Scholar 

  18. Rimola J, Forner A, Reig M, Vilana R, de Lope CR, Ayuso C, et al. Cholangiocarcinoma in cirrhosis: absence of contrast washout in delayed phases by magnetic resonance imaging avoids misdiagnosis of hepatocellular carcinoma. Hepatology. 2009;50:791–8.

    PubMed  Google Scholar 

  19. Vilgrain V. Staging cholangiocarcinoma by imaging studies. HPB (Oxford). 2008;10:106–9.

    CAS  Google Scholar 

  20. Malaguarnera G, Paladina I, Giordano M, Malaguarnera M, Bertino G, Berretta M. Serum markers of intrahepatic cholangiocarcinoma. Dis Markers. 2013;34:219–28.

    PubMed Central  CAS  PubMed  Google Scholar 

  21. Kawarada Y, Mizumoto R. Cholangiocellular carcinoma of the liver. Am J Surg. 1984;147:354–9.

    CAS  PubMed  Google Scholar 

  22. Kawarada Y, Mizumoto R. Diagnosis and treatment of cholangiocellular carcinoma of the liver. Hepatogastroenterology. 1990;37:176–81.

    CAS  PubMed  Google Scholar 

  23. Chalasani N, Baluyut A, Ismail A, Zaman A, Sood G, Ghalib R, et al. Cholangiocarcinoma in patients with primary sclerosing cholangitis: a multicenter case-control study. Hepatology. 2000;31:7–11.

    CAS  PubMed  Google Scholar 

  24. Patel AH, Harnois DM, Klee GG, LaRusso NF, Gores GJ. The utility of CA 19-9 in the diagnoses of cholangiocarcinoma in patients without primary sclerosing cholangitis. Am J Gastroenterol. 2000;95:204–7.

    CAS  PubMed  Google Scholar 

  25. Levy C, Lymp J, Angulo P, Gores GJ, Larusso N, Lindor KD. The value of serum CA 19-9 in predicting cholangiocarcinomas in patients with primary sclerosing cholangitis. Dig Dis Sci. 2005;50:1734–40.

    CAS  PubMed  Google Scholar 

  26. Briggs CD, Neal CP, Mann CD, Steward WP, Manson MM, Berry DP. Prognostic molecular markers in cholangiocarcinoma: a systematic review. Eur J Cancer. 2009;45:33–47.

    CAS  PubMed  Google Scholar 

  27. Shen WF, Zhong W, Xu F, Kan T, Geng L, Xie F, et al. Clinicopathological and prognostic analysis of 429 patients with intrahepatic cholangiocarcinoma. World J Gastroenterol. 2009;15:5976–82.

    PubMed Central  CAS  PubMed  Google Scholar 

  28. Tao LY, Cai L, He XD, Liu W, Qu Q. Comparison of serum tumor markers for intrahepatic cholangiocarcinoma and hepatocellular carcinoma. Am Surg. 2010;76:1210–3.

    PubMed  Google Scholar 

  29. Uenishi T, Kubo S, Hirohashi K, Tanaka H, Shuto T, Yamamoto T, et al. Cytokeratin-19 fragments in serum (cyfra 21-1) as a marker in primary liver cancer. Br J Cancer. 2003;88:1894–9.

    PubMed Central  CAS  PubMed  Google Scholar 

  30. Uenishi T, Yamazaki O, Tanaka H, Takemura S, Yamamoto T, Tanaka S, et al. Serum cytokeratin 19 fragment (cyfra21-1) as a prognostic factor in intrahepatic cholangiocarcinoma. Ann Surg Oncol. 2008;15:583–9.

    PubMed  Google Scholar 

  31. Miwa S, Miyagawa S, Kobayashi A, Akahane Y, Nakata T, Mihara M, et al. Predictive factors for intrahepatic cholangiocarcinoma recurrence in the liver following surgery. J Gastroenterol. 2006;41:893–900.

    CAS  PubMed  Google Scholar 

  32. Sia D, Tovar V, Moeini A, Llovet JM. Intrahepatic cholangiocarcinoma: pathogenesis and rationale for molecular therapies. Oncogene. 2013;32:4861–70.

    PubMed Central  CAS  PubMed  Google Scholar 

  33. Voss JS, Holtegaard LM, Kerr SE, Fritcher EG, Roberts LR, Gores GJ, et al. Molecular profiling of cholangiocarcinoma shows potential for targeted therapy treatment decisions. Hum Pathol. 2013;44:1216–22.

    CAS  PubMed  Google Scholar 

  34. Zabron A, Edwards RJ, Khan SA. The challenge of cholangiocarcinoma: dissecting the molecular mechanisms of an insidious cancer. Dis Model Mech. 2013;6:281–92.

    PubMed Central  CAS  PubMed  Google Scholar 

  35. Borad MJ, Champion MD, Egan JB, Liang WS, Fonseca R, Bryce AH, et al. Integrated genomic characterization reveals novel, therapeutically relevant drug targets in FGFR and EGFR pathways in sporadic intrahepatic cholangiocarcinoma. PLoS Genet. 2014;10:e1004135.

    PubMed Central  PubMed  Google Scholar 

  36. Igami T, Ebata T, Yokoyama Y, Sugawara G, Takahashi Y, Nagino M. Staging of peripheral-type intrahepatic cholangiocarcinoma: appraisal of the new TNM classification and its modifications. World J Surg. 2011;35:2501–9.

    PubMed  Google Scholar 

  37. Kajiyama K, Maeda T, Takenaka K, Sugimachi K, Tsuneyoshi M. The significance of stromal desmoplasia in intrahepatic cholangiocarcinoma: a special reference of “scirrhous-type” and “nonscirrhous-type” growth. Am J Surg Pathol. 1999;23:892–902.

    CAS  PubMed  Google Scholar 

  38. Nakajima T, Tajima Y, Sugano I, Nagao K, Kondo Y, Wada K. Intrahepatic cholangiocarcinoma with sarcomatous change. Clinicopathologic and immunohistochemical evaluation of seven cases. Cancer. 1993;72:1872–7.

    CAS  PubMed  Google Scholar 

  39. Suh KS, Roh HR, Koh YT, Lee KU, Park YH, Kim SW. Clinicopathologic features of the intraductal growth type of peripheral cholangiocarcinoma. Hepatology. 2000;31:12–7.

    CAS  PubMed  Google Scholar 

  40. Aishima S, Kuroda Y, Nishihara Y, Iguchi T, Taguchi K, Taketomi A, et al. Proposal of progression model for intrahepatic cholangiocarcinoma: clinicopathologic differences between hilar type and peripheral type. Am J Surg Pathol. 2007;31:1059–67.

    PubMed  Google Scholar 

  41. Sasaki A, Aramaki M, Kawano K, Morii Y, Nakashima K, Yoshida T, et al. Intrahepatic peripheral cholangiocarcinoma: mode of spread and choice of surgical treatment. Br J Surg. 1998;85:1206–9.

    CAS  PubMed  Google Scholar 

  42. Chung YE, Kim MJ, Park YN, Choi JY, Pyo JY, Kim YC, et al. Varying appearances of cholangiocarcinoma: radiologic-pathologic correlation. Radiographics. 2009;29:683–700.

    PubMed  Google Scholar 

  43. Razumilava N, Gores GJ. Classification, diagnosis, and management of cholangiocarcinoma. Clin Gastroenterol Hepatol. 2013;11:13–21.e1, quiz e3–4.

    PubMed Central  PubMed  Google Scholar 

  44. Shimada K, Sano T, Sakamoto Y, Esaki M, Kosuge T, Ojima H. Surgical outcomes of the mass-forming plus periductal infiltrating types of intrahepatic cholangiocarcinoma: a comparative study with the typical mass-forming type of intrahepatic cholangiocarcinoma. World J Surg. 2007;31:2016–22.

    PubMed  Google Scholar 

  45. Bosman FT, World Health Organization. WHO classification of tumours of the digestive system. World Health Organization classification of tumours. 4th ed. Lyon: International Agency for Research on Cancer; 2010. p. 417.

    Google Scholar 

  46. Goodman ZD. Neoplasms of the liver. Mod Pathol. 2007;20 Suppl 1:S49–60.

    PubMed  Google Scholar 

  47. Yu TH, Yuan RH, Chen YL, Yang WC, Hsu HC, Jeng YM. Viral hepatitis is associated with intrahepatic cholangiocarcinoma with cholangiolar differentiation and n-cadherin expression. Mod Pathol. 2011;24:810–9.

    CAS  PubMed  Google Scholar 

  48. Terada T, Makimoto K, Terayama N, Suzuki Y, Nakanuma Y. Alpha-smooth muscle actin-positive stromal cells in cholangiocarcinomas, hepatocellular carcinomas and metastatic liver carcinomas. J Hepatol. 1996;24:706–12.

    CAS  PubMed  Google Scholar 

  49. Shimonishi T, Miyazaki K, Nakanuma Y. Cytokeratin profile relates to histological subtypes and intrahepatic location of intrahepatic cholangiocarcinoma and primary sites of metastatic adenocarcinoma of liver. Histopathology. 2000;37:55–63.

    CAS  PubMed  Google Scholar 

  50. Shiota K, Taguchi J, Nakashima O, Nakashima M, Kojiro M. Clinicopathologic study on cholangiolocellular carcinoma. Oncol Rep. 2001;8:263–8.

    CAS  PubMed  Google Scholar 

  51. Komuta M, Spee B, Vander Borght S, De Vos R, Verslype C, Aerts R, et al. Clinicopathological study on cholangiolocellular carcinoma suggesting hepatic progenitor cell origin. Hepatology. 2008;47:1544–56.

    CAS  PubMed  Google Scholar 

  52. Kanamoto M, Yoshizumi T, Ikegami T, Imura S, Morine Y, Ikemoto T, et al. Cholangiolocellular carcinoma containing hepatocellular carcinoma and cholangiocellular carcinoma, extremely rare tumor of the liver: a case report. J Med Invest. 2008;55:161–5.

    PubMed  Google Scholar 

  53. Theise ND, Saxena R, Portmann BC, Thung SN, Yee H, Chiriboga L, et al. The canals of hering and hepatic stem cells in humans. Hepatology. 1999;30:1425–33.

    CAS  PubMed  Google Scholar 

  54. Nakanuma Y, Sasaki M, Ikeda H, Sato Y, Zen Y, Kosaka K, et al. Pathology of peripheral intrahepatic cholangiocarcinoma with reference to tumorigenesis. Hepatol Res. 2008;38:325–34.

    PubMed  Google Scholar 

  55. Nakanuma Y, Sato Y, Harada K, Sasaki M, Xu J, Ikeda H. Pathological classification of intrahepatic cholangiocarcinoma based on a new concept. World J Hepatol. 2010;2:419–27.

    PubMed Central  PubMed  Google Scholar 

  56. Nakanuma Y, Sato Y, Ikeda H, Harada K, Kobayashi M, Sano K, et al. Intrahepatic cholangiocarcinoma with predominant “ductal plate malformation” pattern: a new subtype. Am J Surg Pathol. 2012;36:1629–35.

    PubMed  Google Scholar 

  57. Jeng YM, Chen CL, Hsu HC. Lymphoepithelioma-like cholangiocarcinoma: an Epstein-Barr virus-associated tumor. Am J Surg Pathol. 2001;25:516–20.

    CAS  PubMed  Google Scholar 

  58. Chen TC, Ng KF, Kuo T. Intrahepatic cholangiocarcinoma with lymphoepithelioma-like component. Mod Pathol. 2001;14:527–32.

    CAS  PubMed  Google Scholar 

  59. Lim BJ, Kim KS, Lim JS, Kim MJ, Park C, Park YN. Rhabdoid cholangiocarcinoma: a variant of cholangiocarcinoma with aggressive behavior. Yonsei Med J. 2004;45:543–6.

    PubMed  Google Scholar 

  60. Sugano I, Senda T, Hayashi S, Okaya T, Yamazaki K, Ishida Y. A rhabdoid-mimicking intrahepatic cholangiocarcinoma. Pathol Int. 2013;63:422–4.

    PubMed  Google Scholar 

  61. Nakajima T, Kondo Y, Miyazaki M, Okui K. A histopathologic study of 102 cases of intrahepatic cholangiocarcinoma: histologic classification and modes of spreading. Hum Pathol. 1988;19:1228–34.

    CAS  PubMed  Google Scholar 

  62. Chow LT, Ahuja AT, Kwong KH, Fung KS, Lai CK, Lau JW. Mucinous cholangiocarcinoma: an unusual complication of hepatolithiasis and recurrent pyogenic cholangitis. Histopathology. 1997;30:491–4.

    CAS  PubMed  Google Scholar 

  63. Tsou YK, Wu RC, Hung CF, Lee CS. Intrahepatic sarcomatoid cholangiocarcinoma: clinical analysis of seven cases during a 15-year period. Chang Gung Med J. 2008;31:599–605.

    PubMed  Google Scholar 

  64. Shinojima Y, Toma Y, Terui T. Sweet syndrome associated with intrahepatic cholangiocarcinoma producing granulocyte colony-stimulating factor. Br J Dermatol. 2006;155:1103–4.

    CAS  PubMed  Google Scholar 

  65. Takenaka M, Akiba J, Kawaguchi T, Niizeki T, Arinaga-Hino T, Sata M, et al. Intrahepatic cholangiocarcinoma with sarcomatous change producing granulocyte-colony stimulating factor. Pathol Int. 2013;63:233–5.

    CAS  PubMed  Google Scholar 

  66. Sasaki M, Tsuneyama K, Ishikawa A, Nakanuma Y. Intrahepatic cholangiocarcinoma in cirrhosis presents granulocyte and granulocyte-macrophage colony-stimulating factor. Hum Pathol. 2003;34:1337–44.

    CAS  PubMed  Google Scholar 

  67. Haas S, Gutgemann I, Wolff M, Fischer HP. Intrahepatic clear cell cholangiocarcinoma: immunohistochemical aspects in a very rare type of cholangiocarcinoma. Am J Surg Pathol. 2007;31:902–6.

    PubMed  Google Scholar 

  68. Castellano-Megias VM, Ibarrola-de Andres C, Colina-Ruizdelgado F. Pathological aspects of so called “hilar cholangiocarcinoma”. World J Gastrointest Oncol. 2013;5:159–70.

    PubMed Central  PubMed  Google Scholar 

  69. Terada T, Kida T, Nakanuma Y, Kurumaya H, Doishita K, Takayanagi N. Intrahepatic cholangiocarcinomas associated with nonbiliary cirrhosis. A clinicopathologic study. J Clin Gastroenterol. 1994;18:335–42.

    CAS  PubMed  Google Scholar 

  70. Ikegami T, Kayashima H, Sadanaga N, Morizono S, Nakashima A, Matsuura H, et al. Composite small cell and mucinous carcinoma originating from the intrahepatic bile duct: report of a case. Surg Today. 2013;43:194–8.

    PubMed  Google Scholar 

  71. Isa T, Kusano T, Muto Y, Furukawa M, Kiyuna M, Toda T. Clinicopathologic features of resected primary adenosquamous carcinomas of the liver. J Clin Gastroenterol. 1997;25:623–7.

    CAS  PubMed  Google Scholar 

  72. Maeda T, Takenaka K, Taguchi K, Kajiyama K, Shirabe K, Shimada M, et al. Adenosquamous carcinoma of the liver: clinicopathologic characteristics and cytokeratin profile. Cancer. 1997;80:364–71.

    CAS  PubMed  Google Scholar 

  73. Takahashi H, Hayakawa H, Tanaka M, Okamura K, Kosaka A, Mizumoto R, et al. Primary adenosquamous carcinoma of liver resected by right trisegmentectomy: report of a case and review of the literature. J Gastroenterol. 1997;32:843–7.

    CAS  PubMed  Google Scholar 

  74. Sasaki M, Nakanuma Y, Nagai Y, Nonomura A. Intrahepatic cholangiocarcinoma with sarcomatous transformation: an autopsy case. J Clin Gastroenterol. 1991;13:220–5.

    CAS  PubMed  Google Scholar 

  75. Bloustein PA, Silverberg SG. Squamous cell carcinoma originating in an hepatic cyst. Case report with a review of the hepatic cyst-carcinoma association. Cancer. 1976;38:2002–5.

    CAS  PubMed  Google Scholar 

  76. Gresham GA, Rue III LW. Squamous cell carcinoma of the liver. Hum Pathol. 1985;16:413–6.

    CAS  PubMed  Google Scholar 

  77. Lynch MJ, McLeod MK, Weatherbee L, Gilsdorf JR, Guice KS, Eckhauser FE. Squamous cell cancer of the liver arising from a solitary benign nonparasitic hepatic cyst. Am J Gastroenterol. 1988;83:426–31.

    CAS  PubMed  Google Scholar 

  78. Pliskin A, Cualing H, Stenger RJ. Primary squamous cell carcinoma originating in congenital cysts of the liver. Report of a case and review of the literature. Arch Pathol Lab Med. 1992;116:105–7.

    CAS  PubMed  Google Scholar 

  79. Imazu H, Ochiai M, Funabiki T. Intrahepatic sarcomatous cholangiocarcinoma. J Gastroenterol. 1995;30:677–82.

    CAS  PubMed  Google Scholar 

  80. Fan XS, Chen J, Wu HY, Qiu YD, Zhang WW, Kong WT. Intrahepatic sarcomatoid cholangiocarcinoma with osteoclast-like giant cells: report of a case. Zhonghua Bing Li Xue Za Zhi. 2010;39:640–1.

    PubMed  Google Scholar 

  81. Zen Y, Fujii T, Itatsu K, Nakamura K, Minato H, Kasashima S, et al. Biliary papillary tumors share pathological features with intraductal papillary mucinous neoplasm of the pancreas. Hepatology. 2006;44:1333–43.

    CAS  PubMed  Google Scholar 

  82. Zen Y, Sasaki M, Fujii T, Chen TC, Chen MF, Yeh TS, et al. Different expression patterns of mucin core proteins and cytokeratins during intrahepatic cholangiocarcinogenesis from biliary intraepithelial neoplasia and intraductal papillary neoplasm of the bile duct–an immunohistochemical study of 110 cases of hepatolithiasi. J Hepatol. 2006;44:350–8.

    CAS  PubMed  Google Scholar 

  83. Khan SA, Davidson BR, Goldin RD, Heaton N, Karani J, Pereira SP, et al. Guidelines for the diagnosis and treatment of cholangiocarcinoma: an update. Gut. 2012;61:1657–69.

    CAS  PubMed  Google Scholar 

  84. Nuzzo G, Giuliante F, Ardito F, De Rose AM, Vellone M, Clemente G, et al. Intrahepatic cholangiocarcinoma: prognostic factors after liver resection. Updates Surg. 2010;62:11–9.

    PubMed  Google Scholar 

  85. Roayaie S, Guarrera JV, Ye MQ, Thung SN, Emre S, Fishbein TM, et al. Aggressive surgical treatment of intrahepatic cholangiocarcinoma: predictors of outcomes. J Am Coll Surg. 1998;187:365–72.

    CAS  PubMed  Google Scholar 

  86. Chan ES, Yeh MM. The use of immunohistochemistry in liver tumors. Clin Liver Dis. 2010;14:687–703.

    PubMed  Google Scholar 

  87. Rullier A, Le Bail B, Fawaz R, Blanc JF, Saric J, Bioulac-Sage P. Cytokeratin 7 and 20 expression in cholangiocarcinomas varies along the biliary tract but still differs from that in colorectal carcinoma metastasis. Am J Surg Pathol. 2000;24:870–6.

    CAS  PubMed  Google Scholar 

  88. Kozaka K, Sasaki M, Fujii T, Harada K, Zen Y, Sato Y, et al. A subgroup of intrahepatic cholangiocarcinoma with an infiltrating replacement growth pattern and a resemblance to reactive proliferating bile ductules: “bile ductular carcinoma”. Histopathology. 2007;51:390–400.

    CAS  PubMed  Google Scholar 

  89. Lee KH, Kim YB, Cho SB, Lee MC, Park CS, Lee JH. Hepatocellular carcinoma with characteristic mucin production: a case report. Cases J. 2009;2:6789.

    PubMed Central  PubMed  Google Scholar 

  90. Leong AS, Sormunen RT, Tsui WM, Liew CT. Hep par 1 and selected antibodies in the immunohistological distinction of hepatocellular carcinoma from cholangiocarcinoma, combined tumours and metastatic carcinoma. Histopathology. 1998;33:318–24.

    CAS  PubMed  Google Scholar 

  91. Radwan NA, Ahmed NS. The diagnostic value of arginase-1 immunostaining in differentiating hepatocellular carcinoma from metastatic carcinoma and cholangiocarcinoma as compared to HepPar-1. Diagn Pathol. 2012;7:149.

    PubMed Central  PubMed  Google Scholar 

  92. Coston WM, Loera S, Lau SK, Ishizawa S, Jiang Z, Wu CL, et al. Distinction of hepatocellular carcinoma from benign hepatic mimickers using glypican-3 and CD34 immunohistochemistry. Am J Surg Pathol. 2008;32:433–44.

    PubMed  Google Scholar 

  93. Libbrecht L, Severi T, Cassiman D, Vander Borght S, Pirenne J, Nevens F, et al. Glypican-3 expression distinguishes small hepatocellular carcinomas from cirrhosis, dysplastic nodules, and focal nodular hyperplasia-like nodules. Am J Surg Pathol. 2006;30:1405–11.

    PubMed  Google Scholar 

  94. Baumhoer D, Tornillo L, Stadlmann S, Roncalli M, Diamantis EK, Terracciano LM. Glypican 3 expression in human nonneoplastic, preneoplastic, and neoplastic tissues: a tissue microarray analysis of 4,387 tissue samples. Am J Clin Pathol. 2008;129:899–906.

    PubMed  Google Scholar 

  95. Mounajjed T, Zhang L, Wu TT. Glypican-3 expression in gastrointestinal and pancreatic epithelial neoplasms. Hum Pathol. 2013;44:542–50.

    CAS  PubMed  Google Scholar 

  96. Lau SK, Prakash S, Geller SA, Alsabeh R. Comparative immunohistochemical profile of hepatocellular carcinoma, cholangiocarcinoma, and metastatic adenocarcinoma. Hum Pathol. 2002;33:1175–81.

    PubMed  Google Scholar 

  97. Tsuji M, Kashihara T, Terada N, Mori H. An immunohistochemical study of hepatic atypical adenomatous hyperplasia, hepatocellular carcinoma, and cholangiocarcinoma with alpha-fetoprotein, carcinoembryonic antigen, CA 19-9, epithelial membrane antigen, and cytokeratins 18 and 19. Pathol Int. 1999;49:310–7.

    CAS  PubMed  Google Scholar 

  98. Rishi M, Kovatich A, Ehya H. Utility of polyclonal and monoclonal antibodies against carcinoembryonic antigen in hepatic fine-needle aspirates. Diagn Cytopathol. 1994;11:358–61, discussion 361–2.

    CAS  PubMed  Google Scholar 

  99. Wang L, Vuolo M, Suhrland MJ, Schlesinger K. Heppar1, moc-31, pcea, mcea and CD10 for distinguishing hepatocellular carcinoma vs. metastatic adenocarcinoma in liver fine needle aspirates. Acta Cytol. 2006;50:257–62.

    PubMed  Google Scholar 

  100. Porcell AI, De Young BR, Proca DM, Frankel WL. Immunohistochemical analysis of hepatocellular and adenocarcinoma in the liver: Moc31 compares favorably with other putative markers. Mod Pathol. 2000;13:773–8.

    CAS  PubMed  Google Scholar 

  101. Makhlouf HR, Ishak KG, Goodman ZD. Epithelioid hemangioendothelioma of the liver: a clinicopathologic study of 137 cases. Cancer. 1999;85:562–82.

    CAS  PubMed  Google Scholar 

  102. Weinreb I, Cunningham KS, Perez-Ordonez B, Hwang DM. CD10 is expressed in most epithelioid hemangioendotheliomas: a potential diagnostic pitfall. Arch Pathol Lab Med. 2009;133:1965–8.

    PubMed  Google Scholar 

  103. Tsui WM, Loo KT, Chow LT, Tse CC. Biliary adenofibroma. A heretofore unrecognized benign biliary tumor of the liver. Am J Surg Pathol. 1993;17:186–92.

    CAS  PubMed  Google Scholar 

  104. Varnholt H, Vauthey JN, Dal Cin P, Marsh Rde W, Bhathal PS, Hughes NR, et al. Biliary adenofibroma: a rare neoplasm of bile duct origin with an indolent behavior. Am J Surg Pathol. 2003;27:693–8.

    PubMed  Google Scholar 

  105. Sempoux C, Fan C, Singh P, Obeidat K, Roayaie S, Schwartz M, et al. Cholangiolocellular carcinoma: an innocent-looking malignant liver tumor mimicking ductular reaction. Semin Liver Dis. 2011;31:104–10.

    PubMed  Google Scholar 

  106. Liver Cancer Study Group of Japan. Primary liver cancer in Japan. Clinicopathologic features and results of surgical treatment. Ann Surg. 1990;211:277–87.

    Google Scholar 

  107. Aoki K, Takayasu K, Kawano T, Muramatsu Y, Moriyama N, Wakao F, et al. Combined hepatocellular carcinoma and cholangiocarcinoma: clinical features and computed tomographic findings. Hepatology. 1993;18:1090–5.

    CAS  PubMed  Google Scholar 

  108. Maeda T, Adachi E, Kajiyama K, Sugimachi K, Tsuneyoshi M. Combined hepatocellular and cholangiocarcinoma: proposed criteria according to cytokeratin expression and analysis of clinicopathologic features. Hum Pathol. 1995;26:956–64.

    CAS  PubMed  Google Scholar 

  109. Lee WS, Lee KW, Heo JS, Kim SJ, Choi SH, Kim YI, et al. Comparison of combined hepatocellular and cholangiocarcinoma with hepatocellular carcinoma and intrahepatic cholangiocarcinoma. Surg Today. 2006;36:892–7.

    PubMed  Google Scholar 

  110. Yeh MM. Pathology of combined hepatocellular-cholangiocarcinoma. J Gastroenterol Hepatol. 2010;25:1485–92.

    PubMed  Google Scholar 

  111. Cazals-Hatem D, Rebouissou S, Bioulac-Sage P, Bluteau O, Blanché H, Franco D, et al. Clinical and molecular analysis of combined hepatocellular-cholangiocarcinomas. J Hepatol. 2004;41:292–8.

    CAS  PubMed  Google Scholar 

  112. Jarnagin WR, Weber S, Tickoo SK, Koea JB, Obiekwe S, Fong Y, et al. Combined hepatocellular and cholangiocarcinoma: demographic, clinical, and prognostic factors. Cancer. 2002;94:2040–6.

    PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  114. Tanaka S, Yamamoto T, Tanaka H, Kodai S, Ogawa M, Ichikawa T, et al. Potentiality of combined hepatocellular and intrahepatic cholangiocellular carcinoma originating from a hepatic precursor cell: immunohistochemical evidence. Hepatol Res. 2005;32:52–7.

    CAS  PubMed  Google Scholar 

  115. Theise ND, Yao JL, Harada K, Hytiroglou P, Portmann B, Thung SN, et al. Hepatic “stem cell” malignancies in adults: four cases. Histopathology. 2003;43:263–71.

    CAS  PubMed  Google Scholar 

  116. Koh KC, Lee H, Choi MS, Lee JH, Paik SW, Yoo BC, et al. Clinicopathologic features and prognosis of combined hepatocellular cholangiocarcinoma. Am J Surg. 2005;189:120–5.

    PubMed  Google Scholar 

  117. Zuo HQ, Yan LN, Zeng Y, Yang JY, Luo HZ, Liu JW, et al. Clinicopathological characteristics of 15 patients with combined hepatocellular carcinoma and cholangiocarcinoma. Hepatobiliary Pancreat Dis Int. 2007;6:161–5.

    PubMed  Google Scholar 

  118. Goodman ZD, Ishak KG, Langloss JM, Sesterhenn IA, Rabin L. Combined hepatocellular-cholangiocarcinoma. A histologic and immunohistochemical study. Cancer. 1985;55:124–35.

    CAS  PubMed  Google Scholar 

  119. Anthony PP. Primary carcinoma of the liver: a study of 282 cases in Ugandan Africans. J Pathol. 1973;110:37–48.

    CAS  PubMed  Google Scholar 

  120. Goodman ZD, Terracciano LM, Wee A. In: Hubscher SG, Burt AD, Portmann BC, Ferrell LD, editors. Macsween’s pathology of the liver, vol. 1. New York: Churchill Livingstone; 2011. p. 1032.

    Google Scholar 

  121. Durnez A, Verslype C, Nevens F, Fevery J, Aerts R, Pirenne J, et al. The clinicopathological and prognostic relevance of cytokeratin 7 and 19 expression in hepatocellular carcinoma. A possible progenitor cell origin. Histopathology. 2006;49:138–51.

    CAS  PubMed  Google Scholar 

  122. Klein WM, Molmenti EP, Colombani PM, Grover DS, Schwarz KB, Boitnott J, et al. Primary liver carcinoma arising in people younger than 30 years. Am J Clin Pathol. 2005;124:512–8.

    PubMed  Google Scholar 

  123. Wu PC, Fang JW, Lau VK, Lai CL, Lo CK, Lau JY. Classification of hepatocellular carcinoma according to hepatocellular and biliary differentiation markers. Clinical and biological implications. Am J Pathol. 1996;149:1167–75.

    PubMed Central  CAS  PubMed  Google Scholar 

  124. Tickoo SK, Zee SY, Obiekwe S, Xiao H, Koea J, Robiou C, et al. Combined hepatocellular-cholangiocarcinoma: a histopathologic, immunohistochemical, and in situ hybridization study. Am J Surg Pathol. 2002;26:989–97.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Hilton 11, 200 First St SW, Rochester, MN, 55902, USA

    Taofic Mounajjed M.D.

Authors
  1. Taofic Mounajjed M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Taofic Mounajjed M.D. .

Editor information

Editors and Affiliations

  1. Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA

    Taofic Mounajjed

  2. Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA

    Vishal S. Chandan

  3. Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA

    Michael S. Torbenson

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Mounajjed, T. (2015). Cholangiocarcinoma. In: Mounajjed, T., Chandan, V., Torbenson, M. (eds) Surgical Pathology of Liver Tumors. Springer, Cham. https://doi.org/10.1007/978-3-319-16089-4_10

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-16089-4_10

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-16088-7

  • Online ISBN: 978-3-319-16089-4

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation