Editing Cholangiocarcinoma (section)

==Pathophysiology==
[[File:Digestive system showing bile duct.svg|thumb|Digestive system diagram showing bile duct location.]]

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 hepatic duct]] may be referred to [[:wikt:eponym|eponym]]ously as a [[Klatskin tumor]].<ref>{{cite journal | vauthors = Klatskin G | title = Adenocarcinoma of the Hepatic Duct at Its Bifurcation Within The Porta Hepatis. An Unusual Tumor With Distinctive Clinical And Pathological Features | journal = American Journal of Medicine | volume = 38 | issue = 2 | pages = 241–56 | date = February 1965 | pmid = 14256720 | doi = 10.1016/0002-9343(65)90178-6 }}</ref>

Although cholangiocarcinoma is known to have the histological and molecular features of an [[adenocarcinoma]] of epithelial cells lining the biliary tract, the actual cell of origin is unknown. Recent evidence has suggested that the initial transformed cell that generates the primary tumor may arise from a [[pluripotent]] hepatic [[adult stem cell|stem cell]].<ref>{{cite journal | vauthors = Roskams T | title = Liver stem cells and their implication in hepatocellular and cholangiocarcinoma | journal = Oncogene | volume = 25 | issue = 27 | pages = 3818–22 | date = June 2006 | pmid = 16799623 | doi = 10.1038/sj.onc.1209558 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Liu C, Wang J, Ou QJ | title = Possible stem cell origin of human cholangiocarcinoma | journal = World Journal of Gastroenterology | volume = 10 | issue = 22 | pages = 3374–6 | date = November 2004 | pmid = 15484322 | pmc = 4572317 | doi = 10.3748/wjg.v10.i22.3374 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Sell S, Dunsford HA | title = Evidence for the stem cell origin of hepatocellular carcinoma and cholangiocarcinoma | journal = American Journal of Pathology | volume = 134 | issue = 6 | pages = 1347–63 | date = June 1989 | pmid = 2474256 | pmc = 1879951 }}</ref> 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]].<ref name="targeting">{{cite journal | vauthors = Sirica AE | title = Cholangiocarcinoma: molecular targeting strategies for chemoprevention and therapy | journal = Hepatology | volume = 41 | issue = 1 | pages = 5–15 | date = January 2005 | pmid = 15690474 | doi = 10.1002/hep.20537 | s2cid = 10903371 | doi-access = free }}</ref> [[inflammation|Chronic inflammation]] and obstruction of the bile ducts, and the resulting impaired bile flow, are thought to play a role in this progression.<ref name="targeting" /><ref>{{cite journal | vauthors = Holzinger F, Z'graggen K, Büchler MW | title = Mechanisms of biliary carcinogenesis: a pathogenetic multi-stage cascade towards cholangiocarcinoma | journal = Annals of Oncology | volume = 10 | issue = Suppl 4 | pages = 122–6 | year = 1999 | pmid = 10436802 | doi = 10.1023/A:1008321710719 }}</ref><ref>{{cite journal | vauthors = Gores GJ | title = Cholangiocarcinoma: current concepts and insights | journal = Hepatology | volume = 37 | issue = 5 | pages = 961–9 | date = May 2003 | pmid = 12717374 | doi = 10.1053/jhep.2003.50200 | s2cid = 5441766 }}</ref>

[[Histology|Histologically]], cholangiocarcinomas may vary from [[cellular differentiation|undifferentiated to well-differentiated]]. They are often surrounded by a brisk [[fibrosis|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 [[immunohistochemistry|immunohistochemical]] stain that can distinguish [[malignant]] from [[benign]] biliary ductal tissue, although staining for [[cytokeratin]]s, [[carcinoembryonic antigen]], and [[mucin]]s may aid in diagnosis.<ref name="nejm">{{cite journal | vauthors = de Groen PC, Gores GJ, LaRusso NF, Gunderson LL, Nagorney DM | title = Biliary tract cancers | journal = New England Journal of Medicine | volume = 341 | issue = 18 | pages = 1368–78 | date = October 1999 | pmid = 10536130 | doi = 10.1056/NEJM199910283411807 }}</ref> Most tumors (>90%) are [[adenocarcinoma]]s.<ref name="autogenerated1" />