Adenocarcinoma of the lung pathophysiology: Difference between revisions

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==Pathogenesis==
==Pathogenesis==
* Adenocarcinoma is the most common type of lung cancer found in non-smokers and is usually seen peripherally in the lungs, as opposed to centrally located tumors such as [[small cell lung cancer]] and [[squamous cell]] lung cancer.<ref name="Travis95">{{cite journal |author=Travis WD, Travis LB, Devesa SS |title=Lung cancer |journal=Cancer |volume=75 |issue=1 Suppl |pages=191–202 |date=January 1995|pmid=8000996 |doi= 10.1002/1097-0142(19950101)75:1+<191::AID-CNCR2820751307>3.0.CO;2-Y|url=}}</ref><ref name="Kumar-adenocarcinoma">{{cite book |chapter=Chapter 13, box on morphology of adenocarcinoma |author=Mitchell, Richard Sheppard; Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson |title=Robbins Basic Pathology|publisher=Saunders |location=Philadelphia |isbn=1-4160-2973-7 |edition=8th}}</ref>
* Adenocarcinoma is the most common type of lung cancer found in non-smokers and is usually seen as a peripheral lesion in the [[Lung|lungs]], as compared to centrally located tumors such as [[small cell lung cancer]] and [[squamous cell]] lung cancer.<ref name="Travis95">{{cite journal |author=Travis WD, Travis LB, Devesa SS |title=Lung cancer |journal=Cancer |volume=75 |issue=1 Suppl |pages=191–202 |date=January 1995|pmid=8000996 |doi= 10.1002/1097-0142(19950101)75:1+<191::AID-CNCR2820751307>3.0.CO;2-Y|url=}}</ref><ref name="Kumar-adenocarcinoma">{{cite book |chapter=Chapter 13, box on morphology of adenocarcinoma |author=Mitchell, Richard Sheppard; Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson |title=Robbins Basic Pathology|publisher=Saunders |location=Philadelphia |isbn=1-4160-2973-7 |edition=8th}}</ref>


*Individual susceptibility, active smoking, radon exposure, exposure to high pollution levels, asbestos exposure, occupational or environmental exposure to particular agents or carcinogens contribute to the development of adenocarcinoma of the lung. Hydrocarbons cause damage to the DNA and form DNA adducts. Benzo-A-pyrine has effects on inducing p53 mutations and affects molecular signaling pathways such as AKT.  
*Individual susceptibility, active [[smoking]], [[radon]] exposure, exposure to high pollution levels, [[asbestos]] exposure, occupational or environmental exposure to particular agents or [[Carcinogen|carcinogens]] contribute to the development of adenocarcinoma of the lung. [[Hydrocarbon|Hydrocarbons]] cause damage to the [[DNA]] and form DNA adducts. Benzo-A-pyrine has effects on inducing [[P53 (protein)|p53]] mutations and affects [[Signaling pathway|molecular signaling pathways]] such as [[AKT]].  
*The “multiple hit theory” for adenocarcinoma of the lung states that genetic reproduction is hindered due to the cumulative effect of several toxic insults. Underlying lung disease such as COPD, idiopathic pulmonary fibrosis and tuberculosis may exacerbate also trigger the process.
*The “multiple hit theory” for adenocarcinoma of the lung states that genetic [[reproduction]] is hindered due to the cumulative effect of several toxic insults. Underlying [[lung]] disease such as [[Chronic obstructive pulmonary disease|COPD]], [[idiopathic pulmonary fibrosis]] and [[tuberculosis]] may exacerbate also trigger the process.
*Mutations involving several oncogenes may lead to the development of adenocarcinoma of the lung. These are as follows:
*Mutations involving several [[Oncogene|oncogenes]] may lead to the development of adenocarcinoma of the lung. These are as follows:
**H-ras
**Mutations of [[ras]] (found in thirty percent of cases) affect [[signal transduction]] by affecting [[GTPase]] activity:
**K-ras, also determines patient prognosis
***[[Ras|H-ras]]
**N-ras
***[[Ras|K-ras]], also determines patient prognosis  
**Mutations of ras affect signal transduction by affecting GTPase activity. They are found in 30 percent of cases.
***[[Ras|N-ras]]
**c-myc  
**[[Myc|c-myc]]
**c-raf  
**c-raf  
**Tumor suppressor genes retinoblastoma (Rb) and p53
**[[Tumor suppressor gene|Tumor suppressor genes]] [[Retinoblastoma|retinoblastoma (Rb)]] and [[P53 (protein)|p53]]
**Mutations of APOBEC protein
**Mutations of [[APOBEC1|APOBEC protein]]
==Genetics==
==Genetics==
* Genes involved in the pathogenesis of adenocarcinoma of the lung include:<ref>{{cite book | last = Stewart | first = Bernard | title = World cancer report 2014 | publisher = International Agency for Research on Cancer,Distributed by WHO Press, World Health Organization | location = Lyon, France Geneva, Switzerland | year = 2014 | isbn = 9283204298 }}</ref><ref name="pmid17625570">{{cite journal| author=Soda M, Choi YL, Enomoto M, Takada S, Yamashita Y, Ishikawa S et al.| title=Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. | journal=Nature | year= 2007 | volume= 448 | issue= 7153 | pages= 561-6 | pmid=17625570 | doi=10.1038/nature05945 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17625570  }} </ref><ref name="pmid22919003">{{cite journal| author=Davies KD, Le AT, Theodoro MF, Skokan MC, Aisner DL, Berge EM et al.| title=Identifying and targeting ROS1 gene fusions in non-small cell lung cancer. | journal=Clin Cancer Res | year= 2012 | volume= 18 | issue= 17 | pages= 4570-9 | pmid=22919003 | doi=10.1158/1078-0432.CCR-12-0550 | pmc=PMC3703205 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22919003  }} </ref>
* Genes involved in the pathogenesis of adenocarcinoma of the lung include:<ref>{{cite book | last = Stewart | first = Bernard | title = World cancer report 2014 | publisher = International Agency for Research on Cancer,Distributed by WHO Press, World Health Organization | location = Lyon, France Geneva, Switzerland | year = 2014 | isbn = 9283204298 }}</ref><ref name="pmid17625570">{{cite journal| author=Soda M, Choi YL, Enomoto M, Takada S, Yamashita Y, Ishikawa S et al.| title=Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. | journal=Nature | year= 2007 | volume= 448 | issue= 7153 | pages= 561-6 | pmid=17625570 | doi=10.1038/nature05945 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17625570  }} </ref><ref name="pmid22919003">{{cite journal| author=Davies KD, Le AT, Theodoro MF, Skokan MC, Aisner DL, Berge EM et al.| title=Identifying and targeting ROS1 gene fusions in non-small cell lung cancer. | journal=Clin Cancer Res | year= 2012 | volume= 18 | issue= 17 | pages= 4570-9 | pmid=22919003 | doi=10.1158/1078-0432.CCR-12-0550 | pmc=PMC3703205 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22919003  }} </ref>  
:* [[epidermal growth factor receptor|EGFR]] (7p11)
** [[epidermal growth factor receptor|EGFR]] (7p11)  
:* [[KRAS]] (12p12)
** [[KRAS]] (12p12)  
:* [[BRAF]] (7q34)
** [[BRAF]] (7q34)  
:* PIK3CA (3q26)
** PIK3CA (3q26)  
:* ERBB2 (17q12)
** ERBB2 (17q12)  
:* Translocation EML4/[[anaplastic lymphoma kinase|ALK]]
** Translocation EML4/[[anaplastic lymphoma kinase|ALK]]  
:* Tyrosine kinase fusions
** Tyrosine kinase fusions  
::* ALK (2p23), ROS1 (6q22), and RET (10q11)
** ALK (2p23), ROS1 (6q22), and RET (10q11)
 
==Gross Pathology==
==Gross Pathology==
* Peripheral lesions
* Peripheral lesions

Revision as of 16:41, 2 March 2018

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

Overview

On gross pathology, peripheral multifocal lesions is the characteristic finding of adenocarcinoma of the lung.[1] On microscopic histopathological analysis, nuclear atypia, eccentrically placed nuclei, abundant cytoplasm, and conspicuous nucleoli are characteristic findings of adenocarcinoma of the lung. Genes involved in the pathogenesis of adenocarcinoma of the lung include EGFR, HER2, KRAS, ALK, and BRAF.[2]

Pathogenesis

  • Adenocarcinoma is the most common type of lung cancer found in non-smokers and is usually seen as a peripheral lesion in the lungs, as compared to centrally located tumors such as small cell lung cancer and squamous cell lung cancer.[3][4]

Genetics

  • Genes involved in the pathogenesis of adenocarcinoma of the lung include:[5][6][7]
    • EGFR (7p11)
    • KRAS (12p12)
    • BRAF (7q34)
    • PIK3CA (3q26)
    • ERBB2 (17q12)
    • Translocation EML4/ALK
    • Tyrosine kinase fusions
    • ALK (2p23), ROS1 (6q22), and RET (10q11)

Gross Pathology

  • Peripheral lesions
  • May be multifocal

Gallery

Microscopic Pathology

  • Nuclear atypia
  • Eccentrically placed nuclei
  • Abundant cytoplasm
  • Conspicuous nucleoli
  • Nuclear pseudoinclusions
  • Lack of intercellular bridges

Subtypes[9]

  • Lepidic predominant
  • Tumor grows long the alveolar wall
  • Acinar predominant
  • Berry-shaped glands, smaller than lung acini
  • Papillary predominant
  • Fibrovascular cores
  • Micropapillary predominant
  • Nipple shaped projections without fibrovascular cores
  • Solid predominant
  • Sheet of cells

Gallery

References

  1. Adenocarcinoma of the lung. Librepathology 2015. http://librepathology.org/wiki/index.php/File:Adenocarcinoma_%283950819000%29.jpg
  2. Stewart, Bernard (2014). World cancer report 2014. Lyon, France Geneva, Switzerland: International Agency for Research on Cancer,Distributed by WHO Press, World Health Organization. ISBN 9283204298.
  3. Travis WD, Travis LB, Devesa SS (January 1995). "Lung cancer". Cancer. 75 (1 Suppl): 191–202. doi:10.1002/1097-0142(19950101)75:1+<191::AID-CNCR2820751307>3.0.CO;2-Y. PMID 8000996.
  4. Mitchell, Richard Sheppard; Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson. "Chapter 13, box on morphology of adenocarcinoma". Robbins Basic Pathology (8th ed.). Philadelphia: Saunders. ISBN 1-4160-2973-7.
  5. Stewart, Bernard (2014). World cancer report 2014. Lyon, France Geneva, Switzerland: International Agency for Research on Cancer,Distributed by WHO Press, World Health Organization. ISBN 9283204298.
  6. Soda M, Choi YL, Enomoto M, Takada S, Yamashita Y, Ishikawa S; et al. (2007). "Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer". Nature. 448 (7153): 561–6. doi:10.1038/nature05945. PMID 17625570.
  7. Davies KD, Le AT, Theodoro MF, Skokan MC, Aisner DL, Berge EM; et al. (2012). "Identifying and targeting ROS1 gene fusions in non-small cell lung cancer". Clin Cancer Res. 18 (17): 4570–9. doi:10.1158/1078-0432.CCR-12-0550. PMC 3703205. PMID 22919003.
  8. Adenocarcinoma of the lung. Librepathology 2015. http://librepathology.org/wiki/index.php/File:Adenocarcinoma_%283950819000%29.jpg
  9. Adenocarcinoma of the lung. Librepathology 2015. http://librepathology.org/wiki/index.php/Adenocarcinoma_of_the_lung#Microscopic Accessed on December 20, 2015
  10. Acinar adenocarcinoma. Librepathology 2015. http://librepathology.org/wiki/index.php/File:Mucinous_adenocarcinoma_of_the_lung_--_high_mag.jpg
  11. Mucinous adenocarcinoma. Librepathology 2015. http://librepathology.org/wiki/index.php/File:Acinar_pattern_adenocarcinoma_of_lung_--_intermed_mag.jpg


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