Adenocarcinoma of the lung pathophysiology: Difference between revisions
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==Pathogenesis== | ==Pathogenesis== | ||
* Adenocarcinoma | * 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> | ||
*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. | |||
*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. | |||
*Mutations involving several oncogenes may lead to the development of adenocarcinoma of the lung. These are as follows: | |||
**H-ras | |||
**K-ras, also determines patient prognosis | |||
**N-ras | |||
**Mutations of ras affect signal transduction by affecting GTPase activity. They are found in 30 percent of cases. | |||
**c-myc | |||
**c-raf | |||
**Tumor suppressor genes retinoblastoma (Rb) and p53 | |||
**Mutations of 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> | ||
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* Lack of intercellular bridges | * Lack of intercellular bridges | ||
'''Subtypes'''<ref name=libre>Adenocarcinoma of the lung. Librepathology 2015. http://librepathology.org/wiki/index.php/Adenocarcinoma_of_the_lung#Microscopic Accessed on December 20, 2015</ref> | '''Subtypes'''<ref name="libre">Adenocarcinoma of the lung. Librepathology 2015. http://librepathology.org/wiki/index.php/Adenocarcinoma_of_the_lung#Microscopic Accessed on December 20, 2015</ref> | ||
* Lepidic predominant | * Lepidic predominant | ||
:* Tumor grows long the alveolar wall | :* Tumor grows long the alveolar wall |
Revision as of 16:21, 2 March 2018
Adenocarcinoma of the Lung Microchapters |
Differentiating Adenocarcinoma of the Lung from other Diseases |
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Diagnosis |
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Case Studies |
Adenocarcinoma of the lung pathophysiology On the Web |
American Roentgen Ray Society Images of Adenocarcinoma of the lung pathophysiology |
Risk calculators and risk factors for Adenocarcinoma of the lung pathophysiology |
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 peripherally in the lungs, as opposed to centrally located tumors such as small cell lung cancer and squamous cell lung cancer.[3][4]
- 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.
- 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.
- Mutations involving several oncogenes may lead to the development of adenocarcinoma of the lung. These are as follows:
- H-ras
- K-ras, also determines patient prognosis
- N-ras
- Mutations of ras affect signal transduction by affecting GTPase activity. They are found in 30 percent of cases.
- c-myc
- c-raf
- Tumor suppressor genes retinoblastoma (Rb) and p53
- Mutations of APOBEC protein
Genetics
- 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
-
his subpleural lesion consists mostly of pigmented scar tissue with gray-tan tumor seen predominantly at the periphery.The visceral pleura overlying the tumor is retracted due to traction by underlying scar tissue. This is a good example of what has been called "scar carcinoma". In almost all cases of this type the scar is not a pre-existing lesion but rather represents a desmoplastic reponse to the tumor cells. The basal visceral pleura is involved by tumor[8]
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
-
Micrograph of mucinous adenocarcinoma of the lung. H&E stain. [10]
-
Micrograph showing an adenocarcinoma of the lung (acinar pattern). H&E stain. [11]
References
- ↑ Adenocarcinoma of the lung. Librepathology 2015. http://librepathology.org/wiki/index.php/File:Adenocarcinoma_%283950819000%29.jpg
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ Adenocarcinoma of the lung. Librepathology 2015. http://librepathology.org/wiki/index.php/File:Adenocarcinoma_%283950819000%29.jpg
- ↑ Adenocarcinoma of the lung. Librepathology 2015. http://librepathology.org/wiki/index.php/Adenocarcinoma_of_the_lung#Microscopic Accessed on December 20, 2015
- ↑ Acinar adenocarcinoma. Librepathology 2015. http://librepathology.org/wiki/index.php/File:Mucinous_adenocarcinoma_of_the_lung_--_high_mag.jpg
- ↑ Mucinous adenocarcinoma. Librepathology 2015. http://librepathology.org/wiki/index.php/File:Acinar_pattern_adenocarcinoma_of_lung_--_intermed_mag.jpg