Cholangiocarcinoma pathophysiology
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Shivali Marketkar, M.B.B.S. [2]
Overview
Pathophysiology
- The cell of origin of cholangiocarcinoma is unknown. However, some studies has suggested that it may arise from a pluripotent hepatic stem cell.[1][2][3]
- Cholangiocarcinoma is thought to develop through a series of stages from early hyperplasia, metaplasia, dysplasia, to the development of frank carcinoma in a process similar to that observed in the development of colon cancer.[4]
- In specimens of bile ducts from patients with hepatolithiasis, biliary intraepithelial neoplasia is common finding and is considered to be a precursor lesion of cholangiocarcinoma.[5]
- Chronic inflammation, obstruction of the bile ducts, and the resulting impaired bile flow, are thought to play a role in the progression of cancer.[4][6][7]
Gross Pathology
On gross pathology, cholangiocarcinomas are sclerotic masses without hemorrhage or macroscopic necrosis. Cholangicarcinomas may be classified according to macroscopic growth pattern into three subtypes:[5]
Mass-forming: Intrahepatic exophytic nodular (peripheral) tumors are most commonly of the mass-forming subtype. They demonstrate variable amounts of central fibrosis.
Periductal infiltrating: Periductal infiltrating intrahepatic tumors are most common at the hilum, where they are known as Klatskin tumor. It can be present in combination with mass forming tumors within the liver. Growth along the walls of the duct may narrow or dilate the duct.
Intraductal: Intraductal tumors make up 8-18% of resected cholangiocarcinomas and a much smaller number of all cholangiocarcinomas (as most are inoperable). They are characterised by alterations in duct calibre, usually duct ectasia with or without a visible mass. If a mass is visible it may be mural or polypoid in shape. The duct dilatation is thought to be due to abundant mucin production.
Microscopic Pathology
- Histologically, cholangiocarcinomas may vary from undifferentiated to well-differentiated.
- They are often surrounded by a brisk fibrotic or desmoplastic tissue. In the presence of extensive fibrosis, it can be difficult to distinguish well-differentiated cholangiocarcinoma from normal reactive epithelium.
- In general, the active tumor is at the periphery, with the central portions having been replaced by fibrosis, accounting for the capsular retraction which may be seen in intrahepatic tumors.
Shown below is a micrograph of an intrahepatic cholangiocarcinoma (right of image) adjacent to benign hepatocytes (left of image). H&E stain.
Immunohistochemistry
- There is no entirely specific immunohistochemical stain that can distinguish malignant from benign biliary ductal tissue, although staining for cytokeratin, carcinoembryonic antigen, and mucin may aid in diagnosis.[8] Most tumors (>90%) are adenocarcinomas.[9]
Video
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References
- ↑ Roskams T (2006). "Liver stem cells and their implication in hepatocellular and cholangiocarcinoma". Oncogene. 25 (27): 3818–22. PMID 16799623.
- ↑ Liu C, Wang J, Ou Q (2004). "Possible stem cell origin of human cholangiocarcinoma". World J Gastroenterol. 10 (22): 3374–6. PMID 15484322.
- ↑ Sell S, Dunsford H (1989). "Evidence for the stem cell origin of hepatocellular carcinoma and cholangiocarcinoma". Am J Pathol. 134 (6): 1347–63. PMID 2474256.
- ↑ 4.0 4.1 Sirica A (2005). "Cholangiocarcinoma: molecular targeting strategies for chemoprevention and therapy". Hepatology. 41 (1): 5–15. PMID 15690474.
- ↑ 5.0 5.1 Cholangiocarcinoma. Radiopaedia. http://radiopaedia.org/articles/cholangiocarcinoma
- ↑ Holzinger F, Z'graggen K, Büchler M. "Mechanisms of biliary carcinogenesis: a pathogenetic multi-stage cascade towards cholangiocarcinoma". Ann Oncol. 10 Suppl 4: 122–6. PMID 10436802.
- ↑ Gores G (2003). "Cholangiocarcinoma: current concepts and insights". Hepatology. 37 (5): 961–9. PMID 12717374.
- ↑ de Groen P, Gores G, LaRusso N, Gunderson L, Nagorney D (1999). "Biliary tract cancers". N Engl J Med. 341 (18): 1368–78. PMID 10536130.
- ↑ Henson D, Albores-Saavedra J, Corle D (1992). "Carcinoma of the extrahepatic bile ducts. Histologic types, stage of disease, grade, and survival rates". Cancer. 70 (6): 1498–501. PMID 1516001.