Summary
A few cases of cholangiocarcinoma (CC) related to hepatolithiasis have been reported to date, but the aetiological relationship remains unclear. In an attempt to clarify the relationship between two phenomena, we examined morphologically 12 cases of hepatolithiasis associated with CC and 26 cases of hepatolithiasis without CC, with the aid of immunohistochemical staining for carcinoembryonic antigen (CEA). In the livers where both hepatolithiasis and CC were found, the carcinoma spread along the lumenal surface of the stone-containing bile ducts and invaded the ductal walls. Features of “chronic proliferative cholangitis” which was a basic feature of hepatolithiasis, were found within the bile duct walls where carcinoma was invading. In some cases of chronic proliferative cholangitis with hepatolithiasis in the absence of CC, atypical epithelial hyperplasia was noted. Atypical epithelial hyperplasia was also found in bile ducts adjacent to and remote from CC. Atypical epithelial hyperplasia was positive for CEA. The data lead us to speculate that chronic proliferative cholangitis in the presence of hepatolithiasis can undergo progressive changes to atypical epithelial hyperplasia which may in turn progress to CC.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Albores-Saavedra J, Alcäntra-Vazquez A, Cruz-Ortiz H, Herrera-Goepfert R (1980) The precursor lesions of invasive gallbladder carcinoma. Cancer 45:919–927
Burtin P, Chavanel G, Hirsh-Marie H (1973) Characterization of a second normal glycoprotein that cross-reacts with CEA. J Immunol 111:1926–1928
Connor TH, Cantoli Forte G, Sitra P (1979) Bile as a source of mutagenic metabolities produced in vivo and detected by Salmonella thyphimurium. Environ Mutagenesis 1:269–276
Edmondson HA (1967) Tumors of the gallbladder and extrahepatic bile ducts. AFIP, Sect VII, Fas 26, Washington
Esterly J, Spicer S (1968) Mucin histochemistry of human gallbladder: changes in adenocarcinoma, cystic fibrosis and cholelithiasis. J Natl Cancer Inst 40:1–8
Falchuk KR, Lesser PB, Galdabini JJ, Isselbacher KJ (1976) Cholangiocarcinoma as related to chronic intrahepatic cholangitis and hepatolithiasis. Am J Gastroenterol 66:57–61
Gallagher PJ, Millis RR, Mitchinson MJ (1972) Congenital dilatation of the intrahepatic bile ducts with cholangiocarcinoma. J Clin Pathol 25:804–808
Gerber MA, Thung SN (1978) Carcinoembryonic antigen in normal and diseased liver tissue. Am J Pathol 92:671–680
Gerber MA, Thung SN, Shen S, Stromeyer FW, Ishak KG (1983) Phenotypic characterization of hepatic proliferation. Antigenic expression by proliferating epithelial cellsin fetal liver, massive hepatic necrosis, and nodular transformation of the liver. Am J Pathol 110:70–74
Goldin B, Gorbach S Activation of carcinogens by bacterial and microsomal enzyme system. Gastroenterology 85:200–201
Grundmann E (1983) Classification and clinical consequences of precancerous lesions in the digestive and respiratory tracts. Acta Pathol Jpn 33:195–218
Hou PC (1956) The relationship between primary carcinoma of the liver and infestation with clonorchis sinensis. J Pathol 72:239–246
Hou PC (1964) Primary carcinoma of bile ducts of the liver of the cat (felis catus) infested with clonorchis sinensis. J Pathol Bateriol 87:239–244
Hou PC (1965) Pathological changes in the intrahepatic bile ducts of cats (felis catus) infested with clonorchis sinensis. J Pathol Bacteriol 89:357–364
Jones AW, Shreeve DR (1970) Congenital dilatation of the intrahepatic bile ducts with cholangiocarcinoma. Br Med J 2:277–278
Kameda H (1974) Diseases of the biliary tree (In Japanese). Tokyo, Chugai Igaku
Kinami Y, Noto K, Miyazaki I, Matsubara F (1978) A study of hepatolithiasis related to cholangiocarcinoma (In Japanese). Acta Hepatol Jpn 19:578–583
Krupey J, Wilson T, Freedman SO, Gold P (1972) The preparation of purified carcinoembryonic antigen of the human digestive system from large quantities of tumor tissue. Immunochemistry 9:617–622
Kusama S (1978) Epidemiologic study of hepatolithiasis in Japan (In Japanese): Report from Japanese Study Group of Intrahepatic Bile Duct Lesions, granted by Japanese Health and Welfare Ministry (ed)
Kuwayti K, Baggenstoss AH, Stauffer MH, Priestley JT (1957) Carcinoma of the major intrahepatic and the extrahepatic bile ducts exclusive of the papilla of Vater. Surg Gynecol Obstet 104:357–366
Mach JP, Pusztszeri G (1972) Carcinoembryonic antigen (CEA): Demonstration of a partial identity between CEA and a normal glycoprotein. Immunochemistry 9:1031–1034
Migita S (1979) Method of experimental immunology (In Japanese). Maeda Inc., Kanazawa
Nagase M, Hikasa Y, Soloway RD, Tanimura H, Setoyama M, Kato H (1980) Gallstones in western Japan. Factors affecting the prevalence of intrahepatic gallstones. Gastroenterology 78:684–690
Phinney PR, Austin GE, Kadell BM (1981) Cholangiocarcinoma arising in Caroli's disease. Arch Pathol Lab Med 105:194–197
Reddy BS, Watanabe K (1979) Effect of cholesterol metabolites and promoting effect of lithocholic acid in colon carcinogenesis in germfree and conventional F 344 rats. Can Res 39:1521–1524
Sanes S, MacCallum JD (1942) Primary carcinoma of the liver cholangioma in hepatolithiasis. Am J Pathol 18:675–683
Sternberger LA (1979) Immunohistochemistry, 2nd ed. John Witey & Sons Inc, New York
Svenberg T (1976) Carcinoembryonic antigen-like substances of human bile. Isolation and partial characterization. Int J Cancer 17:588–596
Tanaka Y (1982) Immunohistochemical study on carcinoembryonic antigen and its related antigens in primary hepatic cancer (In Japanese) J Juzen Med Soc 91:727–743
Taylor CR (1976) An immunological study of follicular lymphoma, reticulum cell sarcoma and Hodgkin's disease. Eur J Cancer 12:61–75
Wagener C, Csaszar H, Totovic V, Breuer H (1978) A highly sensitive method for the demonstration of carcinoembryonic antigen in normal and neoplastic colon tissue. Histochemistry 58:1–11
Yamamoto K (1982) Intrahepatic periductal glands and their significance in primary intrahepatic lithiasis. Jap J Surg 12:163–170
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Nakanuma, Y., Terada, T., Tanaka, Y. et al. Are hepatolithiasis and cholangiocarcinoma aetiologically related?. Vichows Archiv A Pathol Anat 406, 45–58 (1985). https://doi.org/10.1007/BF00710556
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00710556