Esophageal cancer pathophysiology: Difference between revisions

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__NOTOC__
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{{Esophageal cancer}}
{{Esophageal cancer}}
{{CMG}}{{AE}}{{HM}}
{{CMG}} {{AE}}{{HM}}


==Overview==
==Overview==
The pathophysiology of esophageal cancer depends on the histological subtype.
The pathophysiology of [[esophageal cancer]] depends on the [[Histology|histological]] subtype, whether [[squamous cell carcinoma]] or [[adenocarcinoma]].


==Pathophysiology==
==Pathophysiology==


The esophagus is lined by nonkeratinized stratified squamous epithelium. This lining is maintained as long as there are no stressors leading to a metaplastic change. These stressors may include genetic factors, chronic alcoholism, smoking, ingesting spicy foods and hot liquids frequently, and chronic gastroesophageal reflux. Over time a dysplastic change occurs followed by a metaplastic change which may be of the squamous cell or adenocarcinoma type.<ref name="pmid29037468">{{cite journal |vauthors=Quante M, Graham TA, Jansen M |title=Insights into the Pathophysiology of Esophageal Adenocarcinoma |journal=Gastroenterology |volume= |issue= |pages= |year=2017 |pmid=29037468 |doi=10.1053/j.gastro.2017.09.046 |url=}}</ref>  
*The [[esophagus]] is lined by nonkeratinized stratified [[Squamous epithelium|squamous]] [[epithelium]].  
*This lining is maintained as long as there are no risk factors that can lead to a [[Metaplasia|metaplastic]] change.
 
===Esophageal Squamous Cell Carcinoma===
*The risk factors for esophageal [[squamous cell carcinoma]] include [[smoking]] and [[alcohol]].<ref name="pmid24834141">{{cite journal |vauthors=Napier KJ, Scheerer M, Misra S |title=Esophageal cancer: A Review of epidemiology, pathogenesis, staging workup and treatment modalities |journal=World J Gastrointest Oncol |volume=6 |issue=5 |pages=112–20 |year=2014 |pmid=24834141 |pmc=4021327 |doi=10.4251/wjgo.v6.i5.112 |url=}}</ref><ref name="pmid22320939">{{cite journal |vauthors=Mao WM, Zheng WH, Ling ZQ |title=Epidemiologic risk factors for esophageal cancer development |journal=Asian Pac. J. Cancer Prev. |volume=12 |issue=10 |pages=2461–6 |year=2011 |pmid=22320939 |doi= |url=}}</ref>
*When [[alcohol]] and [[tobacco]] are combined they have a synergistic effect and the risk for esophageal squamous cell carcinoma is higher.
*[[Alcohol]] is able to dissolve fat soluble compounds, like that of the esophageal epithelium.
*Tobacco carcinogens such as [[Aromatic amine|aromatic amines]], [[Nitrosamine|nitrosamines]] and [[Polycyclic aromatic hydrocarbon|polycyclic hydrocarbons]] are, therefore, able to penetrate the esophageal [[epithelium]] deeper when in the presence of [[alcohol]].
*[[Alcohol]] is also able to decrease the metabolic activities of epithelial cells by damaging DNA.
*When the cellular DNA is damaged, the cell cannot undergo [[detoxification]] and protect itself from [[Oxidative stress|oxidative damage]].
*[[Oxidative stress|Oxidation]] leads to inflammation of the [[squamous epithelium]].
*Continuous irritation of the epithelium leads to [[dysplasia]] and [[in situ]] [[malignant]] transformation.
 
===Esophageal Adenocarcinoma===
 
*The risk factors for esophageal [[adenocarcinoma]] include [[gastroesophageal reflux disease]] and [[obesity]].<ref name="pmid8578231">{{cite journal |vauthors=Tilanus HW |title=Changing patterns in the treatment of carcinoma of the esophagus |journal=Scand. J. Gastroenterol. Suppl. |volume=212 |issue= |pages=38–42 |year=1995 |pmid=8578231 |doi= |url=}}</ref><ref name="pmid10233832">{{cite journal |vauthors=Jankowski JA, Wright NA, Meltzer SJ, Triadafilopoulos G, Geboes K, Casson AG, Kerr D, Young LS |title=Molecular evolution of the metaplasia-dysplasia-adenocarcinoma sequence in the esophagus |journal=Am. J. Pathol. |volume=154 |issue=4 |pages=965–73 |year=1999 |pmid=10233832 |pmc=1866556 |doi=10.1016/S0002-9440(10)65346-1 |url=}}</ref><ref name="pmid16299787">{{cite journal |vauthors=Koppert LB, Wijnhoven BP, van Dekken H, Tilanus HW, Dinjens WN |title=The molecular biology of esophageal adenocarcinoma |journal=J Surg Oncol |volume=92 |issue=3 |pages=169–90 |year=2005 |pmid=16299787 |doi=10.1002/jso.20359 |url=}}</ref><ref name="pmid8998117">{{cite journal |vauthors=Ireland AP, Clark GW, DeMeester TR |title=Barrett's esophagus. The significance of p53 in clinical practice |journal=Ann. Surg. |volume=225 |issue=1 |pages=17–30 |year=1997 |pmid=8998117 |pmc=1190601 |doi= |url=}}</ref><ref name="pmid23500888">{{cite journal |vauthors=Nieman KM, Romero IL, Van Houten B, Lengyel E |title=Adipose tissue and adipocytes support tumorigenesis and metastasis |journal=Biochim. Biophys. Acta |volume=1831 |issue=10 |pages=1533–41 |year=2013 |pmid=23500888 |pmc=3742583 |doi=10.1016/j.bbalip.2013.02.010 |url=}}</ref>
*The chronic [[Gastroesophageal reflux disease|reflux of gastric acid]] and [[bile]] at the [[Cardia|gastroesophageal junction]] leads to the irritation of [[squamous epithelium]] lining the esophagus.
*Chronic irritation leads to [[metaplasia]] of esophagus.
*The lining of the esophagus changes from non-keratinized stratified [[Squamous epithelium|squamous]] [[epithelium]] to [[Columnar epithelia|columnar epithelium]].
*This condition is called [[Barrett's esophagus]] .
*The progression of [[Barrett's esophagus]] to [[adenocarcinoma]] is associated with changes in genetic and protein structure, as well as [[gene expression]].
*These mutations include:
**Chromosomal losses (4q, 5q, 9p, and 18q)<ref name="pmid14657432">{{cite journal |vauthors=Enzinger PC, Mayer RJ |title=Esophageal cancer |journal=N. Engl. J. Med. |volume=349 |issue=23 |pages=2241–52 |year=2003 |pmid=14657432 |doi=10.1056/NEJMra035010 |url=}}</ref>
**Chromosomal gains (8q, 17q, and 20q)
**Gene amplifications (7, 8, and 17q)
**[[P53 (protein)|PT53]] genes and [[P16 (gene)|P16]] genes
**Variants in ADH and/or ALDH2 genes<ref name="pmid21642993">{{cite journal |vauthors=Wu C, Hu Z, He Z, Jia W, Wang F, Zhou Y, Liu Z, Zhan Q, Liu Y, Yu D, Zhai K, Chang J, Qiao Y, Jin G, Liu Z, Shen Y, Guo C, Fu J, Miao X, Tan W, Shen H, Ke Y, Zeng Y, Wu T, Lin D |title=Genome-wide association study identifies three new susceptibility loci for esophageal squamous-cell carcinoma in Chinese populations |journal=Nat. Genet. |volume=43 |issue=7 |pages=679–84 |year=2011 |pmid=21642993 |doi=10.1038/ng.849 |url=}}</ref>
**'''Possibly''' Cyclin D1 (CCND1) G870A polymorphism
*In addition, [[obesity]] is implicated in the development of esophageal [[adenocarcinoma]].<ref name="pmid235008882">{{cite journal |vauthors=Nieman KM, Romero IL, Van Houten B, Lengyel E |title=Adipose tissue and adipocytes support tumorigenesis and metastasis |journal=Biochim. Biophys. Acta |volume=1831 |issue=10 |pages=1533–41 |year=2013 |pmid=23500888 |pmc=3742583 |doi=10.1016/j.bbalip.2013.02.010 |url=}}</ref>
*Patients with [[central obesity]] tend to have [[Hypertrophy (medical)|hypertrophied]] [[Adipocyte|adipocytes]] and inflammatory cells within their fat deposits.
*This creates a microenvironment within the [[adipocyte]] that promotes tumor development through the release of [[Adipokine|adipokines]] and [[Cytokine|cytokines]].
*[[Adipocyte|Adipocytes]] potentiate tumor expansion by supplying energy to support the tumor's growth.


==Pathology==
==Pathology==
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===Gross pathology===
===Gross pathology===


Squamous cell carcinoma or adenocarcinoma of the esophagus may appear as a flat, irregular plaque or a polypoid lesion or an ulcerating, fungating mass.<ref>{{cite book | last = Sugarbaker | first = David | title = Adult chest surgery | publisher = McGraw-Hill Education | location = New York | year = 2015 | isbn = 0071781897 }}</ref>
[[Squamous cell carcinoma]] or [[adenocarcinoma]] of the [[esophagus]] may appear as:<ref>{{cite book | last = Sugarbaker | first = David | title = Adult chest surgery | publisher = McGraw-Hill Education | location = New York | year = 2015 | isbn = 0071781897 }}</ref>


* Flat and irregular [[plaque]]
* Polypoid lesion
* [[Ulcer|Ulcerating]], fungating mass.
** Location:
*** [[Squamous cell carcinoma]] is usually found in the mid-third of the [[esophagus]].
*** [[Adenocarcinoma]] is usually found in the lower third of the [[esophagus]] near the gastric opening.
===Microscopic pathology===
===Microscopic pathology===


====Nuclear atypia of malignancy:====
====Nuclear [[atypia]] of malignancy:====
*Found in both types:
*Found in both types:<ref>{{Cite web | title =Squamous cell carcinoma of the esophagus| url =http://librepathology.org/wiki/index.php/Squamous_cell_carcinoma_of_the_esophagus }}</ref>
**Size variation
**[[Poikilocytosis|Poikilocytosis]]
**Shape variation
**[[Anisocytosis|Anisocytosis]]
**Staining variation
**[[Staining|Staining variation]]
**Mitotic activity
**[[Mitosis|Mitotic activity]]


====Squamous cell carcinoma====
====Squamous cell carcinoma:====


Atypical squamous cells with invasion through the basement membrane:
*Atypical squamous cells invade the [[basement membrane]]
*Cytology:
**Cytology of squamous cells:
**Nucleus - typically central
***Eccentric [[Cell nucleus|nucleus]]
**Mitotic activity
***High mitotic activity
**Cytoplasm - "dense-appearing", typically eosinophilic (may be intensely eosinophilic)
***[[Eosinophilic]] cytoplasm
**Squamous whorls or ''keratin pearls'' may be present<ref>{{Cite web | title =Squamous cell carcinoma of the esophagus
***Squamous whorls or ''keratin pearls''
| url =http://librepathology.org/wiki/index.php/Squamous_cell_carcinoma_of_the_esophagus }}</ref>


[[Image:ssc.jpg|thumb|center|1000px|Esophageal squamous cell carcinoma by Nephron - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=31284085]]
[[Image:ssc.jpg|thumb|center|1000px|Esophageal squamous cell carcinoma by Nephron - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=31284085]]


====Adenocarcinoma<ref>{{Cite web | title =Esophageal adenocarcinoma| url =http://librepathology.org/wiki/index.php/Esophageal_adenocarcinoma#Microscopic }}</ref>====
====Adenocarcinoma====
*Invading cell clusters or glands
*Cribriforming (more than rare) or desmoplasia or "deep" invasion (into submucosa)


*Atypical adenomatous cells show:<ref>{{Cite web | title =Esophageal adenocarcinoma| url =http://librepathology.org/wiki/index.php/Esophageal_adenocarcinoma#Microscopic }}</ref>
**Invading cell clusters or [[Gland|glands]]
**[[Cribriform|Cribriforming]]
**[[Desmoplasia]]
**Invasion into [[submucosa]]


[[Image:Ac.jpg|thumb|center|1000px|Esophageal adenocarcinoma by Nephron - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=12475495]]
[[Image:Ac.jpg|thumb|center|1000px|Esophageal adenocarcinoma by Nephron - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=12475495]]
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Latest revision as of 17:53, 11 January 2018

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Hadeel Maksoud M.D.[2]

Overview

The pathophysiology of esophageal cancer depends on the histological subtype, whether squamous cell carcinoma or adenocarcinoma.

Pathophysiology

Esophageal Squamous Cell Carcinoma

Esophageal Adenocarcinoma

Pathology

Gross pathology

Squamous cell carcinoma or adenocarcinoma of the esophagus may appear as:[11]

Microscopic pathology

Nuclear atypia of malignancy:

Squamous cell carcinoma:

Esophageal squamous cell carcinoma by Nephron - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=31284085

Adenocarcinoma

Esophageal adenocarcinoma by Nephron - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=12475495

References

  1. ↑ Napier KJ, Scheerer M, Misra S (2014). "Esophageal cancer: A Review of epidemiology, pathogenesis, staging workup and treatment modalities". World J Gastrointest Oncol. 6 (5): 112–20. doi:10.4251/wjgo.v6.i5.112. PMC 4021327. PMID 24834141.
  2. ↑ Mao WM, Zheng WH, Ling ZQ (2011). "Epidemiologic risk factors for esophageal cancer development". Asian Pac. J. Cancer Prev. 12 (10): 2461–6. PMID 22320939.
  3. ↑ Tilanus HW (1995). "Changing patterns in the treatment of carcinoma of the esophagus". Scand. J. Gastroenterol. Suppl. 212: 38–42. PMID 8578231.
  4. ↑ Jankowski JA, Wright NA, Meltzer SJ, Triadafilopoulos G, Geboes K, Casson AG, Kerr D, Young LS (1999). "Molecular evolution of the metaplasia-dysplasia-adenocarcinoma sequence in the esophagus". Am. J. Pathol. 154 (4): 965–73. doi:10.1016/S0002-9440(10)65346-1. PMC 1866556. PMID 10233832.
  5. ↑ Koppert LB, Wijnhoven BP, van Dekken H, Tilanus HW, Dinjens WN (2005). "The molecular biology of esophageal adenocarcinoma". J Surg Oncol. 92 (3): 169–90. doi:10.1002/jso.20359. PMID 16299787.
  6. ↑ Ireland AP, Clark GW, DeMeester TR (1997). "Barrett's esophagus. The significance of p53 in clinical practice". Ann. Surg. 225 (1): 17–30. PMC 1190601. PMID 8998117.
  7. ↑ Nieman KM, Romero IL, Van Houten B, Lengyel E (2013). "Adipose tissue and adipocytes support tumorigenesis and metastasis". Biochim. Biophys. Acta. 1831 (10): 1533–41. doi:10.1016/j.bbalip.2013.02.010. PMC 3742583. PMID 23500888.
  8. ↑ Enzinger PC, Mayer RJ (2003). "Esophageal cancer". N. Engl. J. Med. 349 (23): 2241–52. doi:10.1056/NEJMra035010. PMID 14657432.
  9. ↑ Wu C, Hu Z, He Z, Jia W, Wang F, Zhou Y, Liu Z, Zhan Q, Liu Y, Yu D, Zhai K, Chang J, Qiao Y, Jin G, Liu Z, Shen Y, Guo C, Fu J, Miao X, Tan W, Shen H, Ke Y, Zeng Y, Wu T, Lin D (2011). "Genome-wide association study identifies three new susceptibility loci for esophageal squamous-cell carcinoma in Chinese populations". Nat. Genet. 43 (7): 679–84. doi:10.1038/ng.849. PMID 21642993.
  10. ↑ Nieman KM, Romero IL, Van Houten B, Lengyel E (2013). "Adipose tissue and adipocytes support tumorigenesis and metastasis". Biochim. Biophys. Acta. 1831 (10): 1533–41. doi:10.1016/j.bbalip.2013.02.010. PMC 3742583. PMID 23500888.
  11. ↑ Sugarbaker, David (2015). Adult chest surgery. New York: McGraw-Hill Education. ISBN 0071781897.
  12. ↑ "Squamous cell carcinoma of the esophagus".
  13. ↑ "Esophageal adenocarcinoma".


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