Cholangiocarcinoma pathophysiology: Difference between revisions
No edit summary |
No edit summary |
||
| Line 5: | Line 5: | ||
==Pathophysiology== | ==Pathophysiology== | ||
*The cell of origin of cholangiocarcinoma is unknown. However, some studies has suggested that it may arise from a [[pluripotent]] hepatic [[adult stem cell|stem cell]].<ref>{{cite journal |author=Roskams T |title=Liver stem cells and their implication in hepatocellular and cholangiocarcinoma |journal=Oncogene |volume=25 |issue=27 |pages=3818–22 |year=2006 |id=PMID 16799623}}</ref><ref>{{cite journal |author=Liu C, Wang J, Ou Q |title=Possible stem cell origin of human cholangiocarcinoma |journal=World J Gastroenterol |volume=10 |issue=22 |pages=3374–6 |year=2004 |id=PMID 15484322}}</ref><ref>{{cite journal |author=Sell S, Dunsford H |title=Evidence for the stem cell origin of hepatocellular carcinoma and cholangiocarcinoma |journal=Am J Pathol |volume=134 |issue=6 |pages=1347–63 |year=1989 |id=PMID 2474256}}</ref> | *The cell of origin of cholangiocarcinoma is unknown. However, some studies has suggested that it may arise from a [[pluripotent]] hepatic [[adult stem cell|stem cell]].<ref>{{cite journal |author=Roskams T |title=Liver stem cells and their implication in hepatocellular and cholangiocarcinoma |journal=Oncogene |volume=25 |issue=27 |pages=3818–22 |year=2006 |id=PMID 16799623}}</ref><ref>{{cite journal |author=Liu C, Wang J, Ou Q |title=Possible stem cell origin of human cholangiocarcinoma |journal=World J Gastroenterol |volume=10 |issue=22 |pages=3374–6 |year=2004 |id=PMID 15484322}}</ref><ref>{{cite journal |author=Sell S, Dunsford H |title=Evidence for the stem cell origin of hepatocellular carcinoma and cholangiocarcinoma |journal=Am J Pathol |volume=134 |issue=6 |pages=1347–63 |year=1989 |id=PMID 2474256}}</ref> | ||
*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 | *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]].<ref name="targeting">{{cite journal |author=Sirica A |title=Cholangiocarcinoma: molecular targeting strategies for chemoprevention and therapy |journal=Hepatology |volume=41 |issue=1 |pages=5–15 |year=2005 |id=PMID 15690474}}</ref> | ||
*[[inflammation|Chronic inflammation]], obstruction of the bile ducts, and the resulting impaired bile flow, are thought to play a role in the progression of cancer.<ref name="targeting"/><ref>{{cite journal |author=Holzinger F, Z'graggen K, Büchler M |title=Mechanisms of biliary carcinogenesis: a pathogenetic multi-stage cascade towards cholangiocarcinoma |journal=Ann Oncol |volume=10 Suppl 4 |issue= |pages=122-6 |year= |id=PMID 10436802}}</ref><ref>{{cite journal |author=Gores G |title=Cholangiocarcinoma: current concepts and insights |journal=Hepatology |volume=37 |issue=5 |pages=961-9 |year=2003 |id=PMID 12717374}}</ref> | *[[inflammation|Chronic inflammation]], obstruction of the bile ducts, and the resulting impaired bile flow, are thought to play a role in the progression of cancer.<ref name="targeting"/><ref>{{cite journal |author=Holzinger F, Z'graggen K, Büchler M |title=Mechanisms of biliary carcinogenesis: a pathogenetic multi-stage cascade towards cholangiocarcinoma |journal=Ann Oncol |volume=10 Suppl 4 |issue= |pages=122-6 |year= |id=PMID 10436802}}</ref><ref>{{cite journal |author=Gores G |title=Cholangiocarcinoma: current concepts and insights |journal=Hepatology |volume=37 |issue=5 |pages=961-9 |year=2003 |id=PMID 12717374}}</ref> | ||
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]].<ref>{{cite journal |author=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=Am J Med |volume=38 |issue= |pages=241-56 |year= |pmid=14256720}}</ref> These tumors block off the bile ducts. | 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]].<ref>{{cite journal |author=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=Am J Med |volume=38 |issue= |pages=241-56 |year= |pmid=14256720}}</ref> These tumors block off the bile ducts. | ||
==Gross Pathology== | |||
On gross pathology, cholangiocarcinomas are sclerotic masses without hemorrhage or macroscopic necrosis. Cholangicarcinomas may be classified according to macroscopic growth pattern into 3 subtypes:<ref name=radio>Cholangiocarcinoma. Radiopaedia. http://radiopaedia.org/articles/cholangiocarcinoma</ref> | |||
'''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. | |||
| Line 16: | Line 26: | ||
===Microscopic Pathology=== | ===Microscopic Pathology=== | ||
Histologically, cholangiocarcinomas are divided into well, moderately and poorly-differentiated adenocarcinomas. 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.<ref name=radio>Cholangiocarcinoma. Radiopaedia. http://radiopaedia.org/articles/cholangiocarcinoma</ref> It is typically a microscopic lesion with a flat or micropapillary dysplastic epithelium. It is synonymous with carcinoma in situ. | |||
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 tumours. | 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 tumours. | ||
Histologically, cholangiocarcinomas are classically well to moderately differentiated. [[Immunohistochemistry]] is useful in the diagnosis and can be used to differentiate a cholangiocarcinoma primary tumor from metastasis of most other gastrointestinal tumours.<ref>{{cite journal |author=Länger F, von Wasielewski R, Kreipe HH |title=[The importance of immunohistochemistry for the diagnosis of cholangiocarcinomas] |language=German |journal=Pathologe |volume=27 |issue=4 |pages=244-50 |year=2006 |pmid=16758167}}</ref> Cytological scrappings are often non-diagnostic. Shown below is a micrograph of an intrahepatic cholangiocarcinoma (right of image) adjacent to benign hepatocytes (left of image). H&E stain. | Histologically, cholangiocarcinomas are classically well to moderately differentiated. [[Immunohistochemistry]] is useful in the diagnosis and can be used to differentiate a cholangiocarcinoma primary tumor from metastasis of most other gastrointestinal tumours.<ref>{{cite journal |author=Länger F, von Wasielewski R, Kreipe HH |title=[The importance of immunohistochemistry for the diagnosis of cholangiocarcinomas] |language=German |journal=Pathologe |volume=27 |issue=4 |pages=244-50 |year=2006 |pmid=16758167}}</ref> Cytological scrappings are often non-diagnostic. Shown below is a micrograph of an intrahepatic cholangiocarcinoma (right of image) adjacent to benign hepatocytes (left of image). H&E stain. | ||
| Line 22: | Line 32: | ||
[[Image:800px-Cholangiocarcinoma_-_very_high_mag.jpg|200px]] | [[Image:800px-Cholangiocarcinoma_-_very_high_mag.jpg|200px]] | ||
In terms of the distribution of large duct (hilar and extrahepatic) tumors: | In terms of the distribution of large duct (hilar and extrahepatic) tumors: | ||
Revision as of 15:01, 29 October 2015
|
Cholangiocarcinoma Microchapters |
|
Diagnosis |
|---|
|
Treatment |
|
Case Studies |
|
Cholangiocarcinoma pathophysiology On the Web |
|
American Roentgen Ray Society Images of Cholangiocarcinoma pathophysiology |
|
Risk calculators and risk factors for Cholangiocarcinoma pathophysiology |
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]
- 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][5][6]
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.[7] These tumors block off the bile ducts.
Gross Pathology
On gross pathology, cholangiocarcinomas are sclerotic masses without hemorrhage or macroscopic necrosis. Cholangicarcinomas may be classified according to macroscopic growth pattern into 3 subtypes:[8] 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.
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.[9] Most tumors (>90%) are adenocarcinomas.[10]
Cancerous tumors of the bile ducts are usually slow-growing and do not spread (metastasize) quickly. However, many of these tumors are already advanced by the time they are found.
Microscopic Pathology
Histologically, cholangiocarcinomas are divided into well, moderately and poorly-differentiated adenocarcinomas. 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.[8] It is typically a microscopic lesion with a flat or micropapillary dysplastic epithelium. It is synonymous with carcinoma in situ. 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 tumours. Histologically, cholangiocarcinomas are classically well to moderately differentiated. Immunohistochemistry is useful in the diagnosis and can be used to differentiate a cholangiocarcinoma primary tumor from metastasis of most other gastrointestinal tumours.[11] Cytological scrappings are often non-diagnostic. Shown below is a micrograph of an intrahepatic cholangiocarcinoma (right of image) adjacent to benign hepatocytes (left of image). H&E stain.
In terms of the distribution of large duct (hilar and extrahepatic) tumors:
- Intrahepatic large ducts: 15%
- Hilum/proximal third of CBD: 50%
- Middle third CBD: 17%
- Distal third CBD: 18%
These tumors are most commonly infiltrating, although both exophytic (mass-forming) and polypoid (intraductal) types are identified. They have similar appearances to their intrahepatic counterparts
Video
{{#ev:youtube|ov5ULXfuJs0}}
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.
- ↑ 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.
- ↑ 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.
- ↑ 8.0 8.1 Cholangiocarcinoma. Radiopaedia. http://radiopaedia.org/articles/cholangiocarcinoma
- ↑ 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.