Esophageal cancer pathophysiology: Difference between revisions

Jump to navigation Jump to search
VisualWikitext
No edit summary
 
(17 intermediate revisions by 2 users not shown)
Line 4: Line 4:


==Overview==
==Overview==
The pathophysiology of [[esophageal cancer]] depends on the [[Histology|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|squamous]] [[epithelium]]. This lining is maintained as long as there are no stressors leading to a [[Metaplasia|metaplastic]] change. These stressors may include [[Genetics|genetic]] factors, chronic [[alcoholism]], [[smoking]], ingesting spicy foods and hot liquids frequently, and [[Gastroesophageal reflux disease|chronic gastroesophageal reflux]]. Eventually, a [[Dysplasia|dysplastic]] change occurs followed by a [[Metaplasia|metaplastic]] change, which may be [[Squamous cell carcinoma|squamous cell]] carcinoma or [[adenocarcinoma]].<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==
Line 20: Line 51:
* [[Ulcer|Ulcerating]], fungating mass.  
* [[Ulcer|Ulcerating]], fungating mass.  
** Location:
** Location:
*** Squamous cell carcinoma is usually found in the mid-third of the esophagus
*** [[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.
*** [[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>
**[[Pleomorphism|Size variation]]
**[[Poikilocytosis|Poikilocytosis]]
**[[Pleomorphism|Shape variation]]
**[[Anisocytosis|Anisocytosis]]
**[[Staining|Staining variation]]
**[[Staining|Staining variation]]
**[[Mitosis|Mitotic activity]]
**[[Mitosis|Mitotic activity]]


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


*Atypical squamous cells invade the [[basement membrane]] <ref>{{Cite web | title =Squamous cell carcinoma of the esophagus| url =http://librepathology.org/wiki/index.php/Squamous_cell_carcinoma_of_the_esophagus }}</ref>
*Atypical squamous cells invade the [[basement membrane]]
**Cytology of squamous cells:
**Cytology of squamous cells:
***Nucleus - typically central
***Eccentric [[Cell nucleus|nucleus]]
***High mitotic activity
***High mitotic activity
***Eosinophilic cytoplasm  
***[[Eosinophilic]] cytoplasm  
***Squamous whorls or ''keratin pearls''
***Squamous whorls or ''keratin pearls''


Line 44: Line 75:
====Adenocarcinoma====
====Adenocarcinoma====


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

Latest revision as of 17:53, 11 January 2018

Esophageal cancer Microchapters

Home

Patient Information

Overview

Historical Perspective

Classification

Pathophysiology

Differentiating Esophageal cancer from other Diseases

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Diagnosis

Diagnostic Study of Choice

History and Symptoms

Physical Examination

Laboratory Findings

Electrocardiogram

X-ray

Echocardiography and Ultrasound

CT

MRI

Other Imaging Findings

Other Diagnostic Studies

Treatment

Medical Therapy

Surgery

Primary Prevention

Secondary Prevention

Cost-Effectiveness of Therapy

Future or Investigational Therapies

Case Studies

Case #1

Esophageal cancer pathophysiology On the Web

Most recent articles

cited articles

Review articles

CME Programs

Powerpoint slides

Images

American Roentgen Ray Society Images of Esophageal cancer pathophysiology

All Images
X-rays
Echo & Ultrasound
CT Images
MRI

Ongoing Trials at Clinical Trials.gov

US National Guidelines Clearinghouse

NICE Guidance

FDA on Esophageal cancer pathophysiology

CDC on Esophageal cancer pathophysiology

Esophageal cancer pathophysiology in the news

Blogs on Esophageal cancer pathophysiology

Directions to Hospitals Treating Esophageal cancer

Risk calculators and risk factors for Esophageal cancer pathophysiology

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".


Template:WikiDoc Sources

Retrieved from "https://www.wikidoc.org/index.php?title=Esophageal_cancer_pathophysiology&oldid=1429452"