Cholangiocarcinoma pathophysiology
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
Pathophysiology
Cholangiocarcinoma can affect any area of the bile ducts, either within or outside the liver. Tumors occurring in the bile ducts within the liver are referred to as intrahepatic; those occurring in the ducts outside the liver are extrahepatic, and tumors occurring at the site where the bile ducts exit the liver may be referred to as perihilar. A cholangiocarcinoma occurring at the junction where the left and right hepatic ducts meet to form the common bile duct may be referred to eponymously as a Klatskin tumor.[1] These tumors block off the bile ducts.
The cell of origin of cholangiocarcinoma is unknown, although recent evidence has suggested that it may arise from a pluripotent hepatic stem cell.[2][3][4] Cholangiocarcinoma is thought to develop through a series of stages — from early hyperplasia and metaplasia, through dysplasia, to the development of frank carcinoma — in a process similar to that seen in the development of colon cancer.[5] Chronic inflammation and obstruction of the bile ducts, and the resulting impaired bile flow, are thought to play a role in this progression.[5][6][7]
Histologically, cholangiocarcinomas may vary from undifferentiated to well-differentiated. They are often surrounded by a brisk fibrotic or desmoplastic tissue response; in the presence of extensive fibrosis, it can be difficult to distinguish well-differentiated cholangiocarcinoma from normal reactive epithelium. There is no entirely specific immunohistochemical stain that can distinguish malignant from benign biliary ductal tissue, although staining for cytokeratins, carcinoembryonic antigen, and mucins may aid in diagnosis.[8] Most tumors (>90%) are adenocarcinomas.[9]
Microscopic Pathology
Histologically, cholangiocarcinomas are classically well to moderately differentiated. Immunohistochemistry is useful in the diagnosis and can be used to differentiate a cholangiocarcinoma primary tumour from metastasis of most other gastrointestinal tumours.[10] Cytological scrappings are often non-diagnostic.
References
- ↑ KLATSKIN G. "ADENOCARCINOMA OF THE HEPATIC DUCT AT ITS BIFURCATION WITHIN THE PORTA HEPATIS. AN UNUSUAL TUMOR WITH DISTINCTIVE CLINICAL AND PATHOLOGICAL FEATURES". Am J Med. 38: 241–56. PMID 14256720.
- ↑ 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.
- ↑ 5.0 5.1 Sirica A (2005). "Cholangiocarcinoma: molecular targeting strategies for chemoprevention and therapy". Hepatology. 41 (1): 5–15. PMID 15690474.
- ↑ 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.
- ↑ Länger F, von Wasielewski R, Kreipe HH (2006). "[The importance of immunohistochemistry for the diagnosis of cholangiocarcinomas]". Pathologe (in German). 27 (4): 244–50. PMID 16758167.