Cholangiocarcinoma pathophysiology: Difference between revisions

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Revision as of 00:40, 4 February 2018

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Farima Kahe M.D. [2] Anmol Pitliya, M.B.B.S. M.D.[3]

Overview

The exact pathogenesis of [disease name] is not fully understood.

OR

It is thought that [disease name] is the result of / is mediated by / is produced by / is caused by either [hypothesis 1], [hypothesis 2], or [hypothesis 3].

OR

[Pathogen name] is usually transmitted via the [transmission route] route to the human host.

OR

Following transmission/ingestion, the [pathogen] uses the [entry site] to invade the [cell name] cell.

OR

[Disease or malignancy name] arises from [cell name]s, which are [cell type] cells that are normally involved in [function of cells].

OR

The progression to [disease name] usually involves the [molecular pathway].

OR

The pathophysiology of [disease/malignancy] depends on the histological subtype.

Pathophysiology

Pathogenesis

The epithelial cell lining the bile ducts are called cholangiocytes. The malignant transformsation of cholangiocytes leads to cholangiocarcinoma.^[1]
Malignant transformation of cholangiocytes into cholangiocarcinoma include following stages:^[2]
1. Hyperplasia
2. Metaplasia
3. Dysplasia
4. Frank carcinoma
Progression of malignancy is believed to be due to:^[2]^[3]^[4]
- Inflammation
- Obstruction of bile ducts
- Biliary intraepithelia neoplasia
Biliary intraepithelial neoplasia is believed to be the initial lesion of cholangiocarcinoma, particularly in patients with hepatolithiasis in bile ducts.

Genetics

Algorithm showing molecular mechanism of cholangiocarcinoma^[5]^[6]^[7]

Cholangiocytes

Proinflammatory cytokines (TNF-α and IL-6)

Several cytokines )

Stimulates the expression of inducible nitric oxide synthase (iNOS) and enhancing NO production

Reactive oxygen species

EGFR (epidermal growth factor receptor) family, specifically the tyrosine kinase ErbB-2 (HER2/neu

Inhibit DNA repair mechanism

Stimulation of cyclooxygenase 2 (COX-2)

Nitrosylation of caspase

Increased invasiveness, proliferation, and mobility of cholangiocytes

Prostaglandin E2 production(Rate limitimg step)

Activate cell cycle of cholangiocytes

Inhibit apoptosis of cholangiocytes

Promotes mutagenesis

Gross Pathology

Gross pathologic features characteristic to intrahepatic cholangiocarcinoma are divided in three subtypes and include:^[8]^[9]^[10]

Mass-forming
- Nodular lesion or mass in the hepatic parenchyma
- Gray to gray-white, firm and solid carcinoma
Periductal infiltrating
- Spreading of the carcinoma along the portal tracts with stricture of the affected bile ducts
- Dilatation of the peripheral bile ducts
Intraductal growth types
- Polypoid or papillary tumor within the variably dilated bile duct lumen
- Malignant progression of an intraductal papillary neoplasm of the bile duct

Intrahepatic cholangiocarcinoma Source: By Banchob Sripa, via Wikimedia Commons^[11]

Cholangiocarcinoma Source: By Sripa B, Kaewkes S, Sithithaworn P, Mairiang E, Laha T, et al, via Wikimedia Commons^[12]

Microscopic Pathology

On microscopic pathology, characteristic findings of cholangiocarcinoma include:

Cuboidal or columnar mucin producing cells
Dense fibrous(desmoplastic) stroma.

Cholangiocarcinoma histopathology Source: By Nephron (Own work), via Wikimedia Commons^[13]

References

↑ Fava, G.; Lorenzini, I. (2012). "Molecular Pathogenesis of Cholangiocarcinoma". International Journal of Hepatology. 2012: 1–7. doi:10.1155/2012/630543. ISSN 2090-3448.
↑ ^2.0 ^2.1 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.
↑ Wadsworth CA, Dixon PH, Wong JH, Chapman MH, McKay SC, Sharif A, Spalding DR, Pereira SP, Thomas HC, Taylor-Robinson SD, Whittaker J, Williamson C, Khan SA (2011). "Genetic factors in the pathogenesis of cholangiocarcinoma". Dig Dis. 29 (1): 93–7. doi:10.1159/000324688. PMC 3696362. PMID 21691113.
↑ Maroni L, Pierantonelli I, Banales JM, Benedetti A, Marzioni M (2013). "The significance of genetics for cholangiocarcinoma development". Ann Transl Med. 1 (3): 28. doi:10.3978/j.issn.2305-5839.2012.10.04. PMC 4200671. PMID 25332972.
↑ Kongpetch S, Jusakul A, Ong CK, Lim WK, Rozen SG, Tan P, Teh BT (2015). "Pathogenesis of cholangiocarcinoma: From genetics to signalling pathways". Best Pract Res Clin Gastroenterol. 29 (2): 233–44. doi:10.1016/j.bpg.2015.02.002. PMID 25966424.
↑ Nakanuma Y, Sato Y, Harada K, Sasaki M, Xu J, Ikeda H (2010). "Pathological classification of intrahepatic cholangiocarcinoma based on a new concept". World J Hepatol. 2 (12): 419–27. doi:10.4254/wjh.v2.i12.419. PMC 3010511. PMID 21191517.
↑ Blechacz B, Komuta M, Roskams T, Gores GJ (2011). "Clinical diagnosis and staging of cholangiocarcinoma". Nat Rev Gastroenterol Hepatol. 8 (9): 512–22. doi:10.1038/nrgastro.2011.131. PMC 3331791. PMID 21808282.
↑ Vijgen S, Terris B, Rubbia-Brandt L (2017). "Pathology of intrahepatic cholangiocarcinoma". Hepatobiliary Surg Nutr. 6 (1): 22–34. doi:10.21037/hbsn.2016.11.04. PMC 5332210. PMID 28261592.
↑ "File:Cholangiocarcinoma.png - Wikimedia Commons". External link in |title= (help)
↑ "File:CCA Cholangiocarcinoma.jpg - Wikimedia Commons".
↑ "File:Cholangiocarcinoma - high mag.jpg - Wikimedia Commons".

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[FavaLorenzini2012-1] Fava, G.; Lorenzini, I. (2012). "Molecular Pathogenesis of Cholangiocarcinoma". International Journal of Hepatology. 2012: 1–7. doi:10.1155/2012/630543. ISSN 2090-3448.

[targeting-2] 2.0 ^2.1 Sirica A (2005). "Cholangiocarcinoma: molecular targeting strategies for chemoprevention and therapy". Hepatology. 41 (1): 5–15. PMID 15690474.

[3] 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.

[4] Gores G (2003). "Cholangiocarcinoma: current concepts and insights". Hepatology. 37 (5): 961–9. PMID 12717374.

[pmid21691113-5] Wadsworth CA, Dixon PH, Wong JH, Chapman MH, McKay SC, Sharif A, Spalding DR, Pereira SP, Thomas HC, Taylor-Robinson SD, Whittaker J, Williamson C, Khan SA (2011). "Genetic factors in the pathogenesis of cholangiocarcinoma". Dig Dis. 29 (1): 93–7. doi:10.1159/000324688. PMC 3696362. PMID 21691113.

[pmid25332972-6] Maroni L, Pierantonelli I, Banales JM, Benedetti A, Marzioni M (2013). "The significance of genetics for cholangiocarcinoma development". Ann Transl Med. 1 (3): 28. doi:10.3978/j.issn.2305-5839.2012.10.04. PMC 4200671. PMID 25332972.

[pmid25966424-7] Kongpetch S, Jusakul A, Ong CK, Lim WK, Rozen SG, Tan P, Teh BT (2015). "Pathogenesis of cholangiocarcinoma: From genetics to signalling pathways". Best Pract Res Clin Gastroenterol. 29 (2): 233–44. doi:10.1016/j.bpg.2015.02.002. PMID 25966424.

[pmid21191517-8] Nakanuma Y, Sato Y, Harada K, Sasaki M, Xu J, Ikeda H (2010). "Pathological classification of intrahepatic cholangiocarcinoma based on a new concept". World J Hepatol. 2 (12): 419–27. doi:10.4254/wjh.v2.i12.419. PMC 3010511. PMID 21191517.

[pmid21808282-9] Blechacz B, Komuta M, Roskams T, Gores GJ (2011). "Clinical diagnosis and staging of cholangiocarcinoma". Nat Rev Gastroenterol Hepatol. 8 (9): 512–22. doi:10.1038/nrgastro.2011.131. PMC 3331791. PMID 21808282.

[pmid28261592-10] Vijgen S, Terris B, Rubbia-Brandt L (2017). "Pathology of intrahepatic cholangiocarcinoma". Hepatobiliary Surg Nutr. 6 (1): 22–34. doi:10.21037/hbsn.2016.11.04. PMC 5332210. PMID 28261592.

[urlFile:Cholangiocarcinoma.png_-_Wikimedia_Commons-11] "File:Cholangiocarcinoma.png - Wikimedia Commons". External link in |title= (help)

[urlFile:CCA_Cholangiocarcinoma.jpg_-_Wikimedia_Commons-12] "File:CCA Cholangiocarcinoma.jpg - Wikimedia Commons".

[urlFile:Cholangiocarcinoma_-_high_mag.jpg_-_Wikimedia_Commons-13] "File:Cholangiocarcinoma - high mag.jpg - Wikimedia Commons".

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+[[File:Cholangiocarcinoma.png|thumb|400px|left|Intrahepatic cholangiocarcinoma [https://commons.wikimedia.org/wiki/File:Cholangiocarcinoma.png Source: By Banchob Sripa, via Wikimedia Commons]<ref name="urlFile:Cholangiocarcinoma.png - Wikimedia Commons">{{cite web |url=https://commons.wikimedia.org/wiki/File:Cholangiocarcinoma.png |title=File:Cholangiocarcinoma.png - Wikimedia Commons |format= |work= |accessdate=}}</ref>]]
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