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==Overview== | ==Overview== | ||
Non-small cell lung cancer arises from the [[epithelial]] | Non-small cell lung cancer arises from the [[epithelial cells]] of the [[Bronchiole|bronchioles]] and [[Pulmonary alveolus|alveoli]][[Terminal bronchiole|,]] which are normally involved in the protection of the [[Airway|airways]]. Non-small cell lung cancer is an invasive and rapidly growing [[cancer]] which may [[Metastasis|metastasize]] to different organs of the body. [[Genes]] involved in the [[pathogenesis]] of non-small cell lung cancer include [[EGFR]], [[KRAS]], [[HER2]], [[BRAF]], and ALK. Findings on gross pathology depends on the [[Histopathology|histological subtypes]] of non-small cell lung cancer. On microscopic histopathological analysis non-small cell lung cancer usually demonstrates large cells with abundant cytoplasm and no stippled [[chromatin]]. | ||
==Pathogenesis== | ==Pathogenesis== | ||
The pathogenesis of non-small cell lung cancer depends on the type of histological subtype of lung cancer.<ref name="pmid16107574">{{cite journal |vauthors=Miller YE |title=Pathogenesis of lung cancer: 100 year report |journal=Am. J. Respir. Cell Mol. Biol. |volume=33 |issue=3 |pages=216–23 |year=2005 |pmid=16107574 |pmc=2715312 |doi=10.1165/rcmb.2005-0158OE |url=}}</ref> | The pathogenesis of non-small cell lung cancer depends on the type of histological subtype of lung cancer.<ref name="pmid16107574">{{cite journal |vauthors=Miller YE |title=Pathogenesis of lung cancer: 100 year report |journal=Am. J. Respir. Cell Mol. Biol. |volume=33 |issue=3 |pages=216–23 |year=2005 |pmid=16107574 |pmc=2715312 |doi=10.1165/rcmb.2005-0158OE |url=}}</ref> | ||
*Non-small cell lung cancer arises from the [[epithelial]] cells of the [[Bronchiole|bronchioles]] and [[Pulmonary alveolus|alveoli]][[Terminal bronchiole|,]] which are normally involved in the protection of the airways. | *Non-small cell lung cancer arises from the [[epithelial]] cells of the [[Bronchiole|bronchioles]] and [[Pulmonary alveolus|alveoli]][[Terminal bronchiole|,]] which are normally involved in the protection of the airways. | ||
*The genetic pathogenesis of non-small cell lung cancer is due to the amplification of [[Oncogene|oncogenes]] and inactivation of [[Tumor suppressor gene|tumor suppressor genes.]] | *The genetic [[pathogenesis]] of non-small cell lung cancer is due to the amplification of [[Oncogene|oncogenes]] and inactivation of [[Tumor suppressor gene|tumor suppressor genes.]] | ||
*Non-small cell lung cancer is an invasive and rapidly growing [[cancer]] which may [[Metastasis|metastasize]] to different organs of the body. | *Non-small cell lung cancer is an invasive and rapidly growing [[cancer]] which may [[Metastasis|metastasize]] to different organs of the body. | ||
Pathogenesis according to histopathological subtypes: | [[Pathogenesis]] according to histopathological subtypes: | ||
*'''Adenocarcinoma of the lung:''' | *'''Adenocarcinoma of the lung:'''<ref name="pmid25806193">{{cite journal |vauthors=Thunnissen E |title=Pulmonary adenocarcinoma histology |journal=Transl Lung Cancer Res |volume=1 |issue=4 |pages=276–9 |date=December 2012 |pmid=25806193 |pmc=4367552 |doi=10.3978/j.issn.2218-6751.2012.10.11 |url=}}</ref> | ||
**[[Adenocarcinoma of the lung|Adenocarcinoma]] arises from the bronchial mucosal glands of the lung ([[Bronchus|main, lobar, or segmental bronchi]], or [[Parenchyma|lung parenchyma]]), which are normally involved in eliminating microbes and avoiding microbial growth in the epithelial cells of the lung. | **[[Adenocarcinoma of the lung|Adenocarcinoma]] arises from the bronchial mucosal glands of the lung ([[Bronchus|main, lobar, or segmental bronchi]], or [[Parenchyma|lung parenchyma]]), which are normally involved in eliminating microbes and avoiding microbial growth in the [[epithelial cells]] of the lung. | ||
**[[Adenocarcinoma of the lung|Lung adenocarcinoma]] usually occurs in a peripheral location within the lung. | **[[Adenocarcinoma of the lung|Lung adenocarcinoma]] usually occurs in a peripheral location within the lung. | ||
**In the majority of the patients, [[cancer]] arises from precursor lesions, such as pre-existing scars or [[inflammation]] (chronic infections). | **In the majority of the patients, [[cancer]] arises from precursor lesions, such as pre-existing scars or [[inflammation]] (chronic infections). | ||
**[[Adenocarcinoma of the lung|Lung adenocarcinoma]] can also result from multiple [[Mutation|genetic mutations]]. | **[[Adenocarcinoma of the lung|Lung adenocarcinoma]] can also result from multiple [[Mutation|genetic mutations]]. | ||
**For more information about | **For more information about [[Adenocarcinoma of the lung pathophysiology|adenocarcinoma of the lung pathogenesis]], [[Adenocarcinoma of the lung pathophysiology|click here.]] | ||
*'''Large cell carcinoma of the lung:''' | *'''Large cell carcinoma of the lung:''' | ||
**[[Large cell carcinoma of the lung]] arises from large polygonal and [[Anaplasia|anaplastic]] cells. | **[[Large cell carcinoma of the lung]] arises from large polygonal and [[Anaplasia|anaplastic]] cells. | ||
**It is difficult to differentiate [[Large cell carcinoma of the lung|large cell carcinoma]] from other types of [[non small cell lung cancer]]. | **It is difficult to differentiate [[Large cell carcinoma of the lung|large cell carcinoma]] from other types of [[non small cell lung cancer]]. | ||
**[[Large cell carcinoma of the lung]] usually occurs in a peripheral location within the lung. | **[[Large cell carcinoma of the lung]] usually occurs in a peripheral location within the lung. | ||
**For more information about | **For more information about [[Large cell carcinoma of the lung pathophysiology|large cell carcinoma of the lung pathogenesis]], [[Large cell carcinoma of the lung pathophysiology|click here]]. | ||
*'''Squamous cell carcinoma of the lung:'''<ref name="pmid28815199">{{cite journal |vauthors=Suarez E, Knollmann-Ritschel BEC |title=Squamous Cell Carcinoma of the Lung |journal=Acad Pathol |volume=4 |issue= |pages=2374289517705950 |date=2017 |pmid=28815199 |pmc=5528918 |doi=10.1177/2374289517705950 |url=}}</ref> | |||
**[[Squamous cell carcinoma]] of the lung arises from [[bronchial]] epithelial cell damage, commonly caused by smoking. | |||
**[[Squamous cell carcinoma]] usually occurs in a central location within the lung. | |||
**For more information about [[Squamous cell carcinoma of the lung pathophysiology|squamous cell carcinoma of the lung pathogenesis]], [[Squamous cell carcinoma of the lung pathophysiology|click here.]] | |||
==Genetics== | ==Genetics== | ||
Development of non-small cell lung cancer is the result of multiple [[genetic mutation]]s. Genetic mutations also play an important role in the treatment selection for non small cell lung cancer.<ref name="pmid19466276">{{cite journal |vauthors=Capelozzi VL |title=Role of immunohistochemistry in the diagnosis of lung cancer |journal=J Bras Pneumol |volume=35 |issue=4 |pages=375–82 |year=2009 |pmid=19466276 |doi= |url=}}</ref> | Development of non-small cell lung cancer is the result of multiple [[genetic mutation]]s. [[Genetic mutations]] also play an important role in the treatment selection for non small cell lung cancer.<ref name="pmid19466276">{{cite journal |vauthors=Capelozzi VL |title=Role of immunohistochemistry in the diagnosis of lung cancer |journal=J Bras Pneumol |volume=35 |issue=4 |pages=375–82 |year=2009 |pmid=19466276 |doi= |url=}}</ref> | ||
* The table below describes the [[gene]]s involved in the pathogenesis of non small cell lung cancer. | * The table below describes the [[gene]]s involved in the [[pathogenesis]] of non small cell lung cancer. | ||
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==Gross Pathology== | ==Gross Pathology== | ||
On gross pathology, findings will depend on the histological subtype of non-small cell lung cancer. | On gross pathology, findings will depend on the histological subtype of non-small cell lung cancer. | ||
*'''Adenocarcinoma of the lung:'''<ref name=" | *'''Adenocarcinoma of the lung:'''<ref name="pmid25806193" /><ref name="pmid288151995">{{cite journal |vauthors=Suarez E, Knollmann-Ritschel BEC |title=Squamous Cell Carcinoma of the Lung |journal=Acad Pathol |volume=4 |issue= |pages=2374289517705950 |date=2017 |pmid=28815199 |pmc=5528918 |doi=10.1177/2374289517705950 |url=}}</ref> | ||
**Spherical tumor with well-defined borders | **Spherical tumor with well-defined borders | ||
**Homogeneous gray-white cut surface | **Homogeneous gray-white cut surface | ||
**Involvement of the [[thoracic wall]] | **Involvement of the [[thoracic wall]] | ||
**Usually found in the peripheral lung | **Usually found in the peripheral lung | ||
**For more information on [[Adenocarcinoma of the lung pathophysiology | **For more information on the gross pathological findings of [[Adenocarcinoma of the lung pathophysiology|adenocarcinoma of the lung]], [[Adenocarcinoma of the lung pathophysiology#Gross Pathology|click here]]. | ||
*'''Large cell carcinoma of the lung:'''<ref name=" | *'''Large cell carcinoma of the lung:'''<ref name="pmid161075743">{{cite journal |vauthors=Miller YE |title=Pathogenesis of lung cancer: 100 year report |journal=Am. J. Respir. Cell Mol. Biol. |volume=33 |issue=3 |pages=216–23 |year=2005 |pmid=16107574 |pmc=2715312 |doi=10.1165/rcmb.2005-0158OE |url=}}</ref> | ||
**Well-defined borders | **Well-defined borders | ||
**Resemblance to gross findings in adenocarcinoma | **Resemblance to gross findings in [[Adenocarcinoma of the lung|adenocarcinoma]] | ||
**No signs of [[anthracosis]] | **No signs of [[anthracosis]] | ||
**Involvement of the thoracic wall | **Involvement of the thoracic wall | ||
**For more information on [[Large cell carcinoma of the lung pathophysiology | **For more information on the gross [[pathological]] finding of [[Large cell carcinoma of the lung pathophysiology|large cell carcinoma of the lung,]] [[Large cell carcinoma of the lung pathophysiology#Gross Pathology|click here]]. | ||
*'''Squamous cell carcinoma of the lung:'''<ref name=" | *'''Squamous cell carcinoma of the lung:'''<ref name="pmid288151994">{{cite journal |vauthors=Suarez E, Knollmann-Ritschel BEC |title=Squamous Cell Carcinoma of the Lung |journal=Acad Pathol |volume=4 |issue= |pages=2374289517705950 |date=2017 |pmid=28815199 |pmc=5528918 |doi=10.1177/2374289517705950 |url=}}</ref> | ||
**Lung mass | **Lung mass | ||
**Usually centrally located | **Usually centrally located | ||
**Associated with a large airway | **Associated with a large airway | ||
**Usually have a [[Cavitation|central cavitation]] | **Usually have a [[Cavitation|central cavitation]] | ||
**For more information on [[Squamous cell carcinoma of the lung pathophysiology | **For more information on the gross pathological finding of [[Squamous cell carcinoma of the lung pathophysiology|squamous cell carcinoma of the lung]], [[Squamous cell carcinoma of the lung pathophysiology#Gross Pathology|click here]]. | ||
==Microscopic Pathology== | ==Microscopic Pathology== | ||
On microscopic pathology, findings will depend on the histological type of non-small cell lung cancer. | On microscopic pathology, findings will depend on the histological type of non-small cell lung cancer. | ||
*Lung | *'''Adenocarcinoma of the lung:'''<ref name="pmid288151992">{{cite journal |vauthors=Suarez E, Knollmann-Ritschel BEC |title=Squamous Cell Carcinoma of the Lung |journal=Acad Pathol |volume=4 |issue= |pages=2374289517705950 |date=2017 |pmid=28815199 |pmc=5528918 |doi=10.1177/2374289517705950 |url=}}</ref> | ||
*Nuclear atypia | **Nuclear atypia | ||
*Eccentrically placed nuclei | **Eccentrically placed nuclei | ||
*Abundant cytoplasm with mucin vacuoles | **Abundant [[cytoplasm]] with mucin vacuoles | ||
*Often conspicuous [[nucleoli]] | **Often conspicuous [[nucleoli]] | ||
*Lack of intercellular bridges | **Lack of [[Intercellular space|intercellular]] bridges | ||
*Different patterns, include: acinar, lepidic, micropapillary, papillary, and solid. | **Different patterns, include: [[Acinus|acinar]], lepidic, micropapillary, [[Papilla|papillary]], and solid | ||
**For more information on microscopic pathological findings of [[Adenocarcinoma of the lung pathophysiology|adenocarcinoma of the lung]], [[Adenocarcinoma of the lung pathophysiology#Microscopic Pathology|click here]]. | |||
*Large cell lung | *'''Large cell carcinoma of the lung:'''<ref name="pmid161075743" /> | ||
*Large polygonal cells and anaplastic cells | **Large polygonal cells and [[anaplastic]] cells | ||
*No squamous or glandular differentiation | **No [[squamous]] or [[glandular]] differentiation | ||
*Moderately abundant cytoplasm | **Moderately abundant [[cytoplasm]] | ||
*Vesicular nuclei, prominent nucleoli | **Vesicular nuclei, prominent nucleoli | ||
**For more information on microscopic pathological findings of [[Large cell carcinoma of the lung pathophysiology|large cell carcinoma of the lung]], [[Large cell carcinoma of the lung pathophysiology#Microscopic Pathology|click here.]] | |||
*Squamous cell lung | *'''Squamous cell carcinoma of the lung:'''<ref name="pmid288151993">{{cite journal |vauthors=Suarez E, Knollmann-Ritschel BEC |title=Squamous Cell Carcinoma of the Lung |journal=Acad Pathol |volume=4 |issue= |pages=2374289517705950 |date=2017 |pmid=28815199 |pmc=5528918 |doi=10.1177/2374289517705950 |url=}}</ref> | ||
*Central nucleus | **Central nucleus | ||
*Dense appearing cytoplasm, usually eosinophilic | **Dense appearing cytoplasm, usually eosinophilic | ||
*Small nucleolus | **Small nucleolus | ||
*Intercellular bridges (classic feature) | **Intercellular bridges (classic feature) | ||
**For more information on microscopic pathological findings of [[Squamous cell carcinoma of the lung pathophysiology|squamous cell carcinoma of the lung]], [[Squamous cell carcinoma of the lung#Microscopic Pathology|click here]]. | |||
==References== | ==References== | ||
Latest revision as of 17:46, 28 January 2019
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Trusha Tank, M.D.[2],Maria Fernanda Villarreal, M.D. [3]
Overview
Non-small cell lung cancer arises from the epithelial cells of the bronchioles and alveoli, which are normally involved in the protection of the airways. Non-small cell lung cancer is an invasive and rapidly growing cancer which may metastasize to different organs of the body. Genes involved in the pathogenesis of non-small cell lung cancer include EGFR, KRAS, HER2, BRAF, and ALK. Findings on gross pathology depends on the histological subtypes of non-small cell lung cancer. On microscopic histopathological analysis non-small cell lung cancer usually demonstrates large cells with abundant cytoplasm and no stippled chromatin.
Pathogenesis
The pathogenesis of non-small cell lung cancer depends on the type of histological subtype of lung cancer.[1]
- Non-small cell lung cancer arises from the epithelial cells of the bronchioles and alveoli, which are normally involved in the protection of the airways.
- The genetic pathogenesis of non-small cell lung cancer is due to the amplification of oncogenes and inactivation of tumor suppressor genes.
- Non-small cell lung cancer is an invasive and rapidly growing cancer which may metastasize to different organs of the body.
Pathogenesis according to histopathological subtypes:
- Adenocarcinoma of the lung:[2]
- Adenocarcinoma arises from the bronchial mucosal glands of the lung (main, lobar, or segmental bronchi, or lung parenchyma), which are normally involved in eliminating microbes and avoiding microbial growth in the epithelial cells of the lung.
- Lung adenocarcinoma usually occurs in a peripheral location within the lung.
- In the majority of the patients, cancer arises from precursor lesions, such as pre-existing scars or inflammation (chronic infections).
- Lung adenocarcinoma can also result from multiple genetic mutations.
- For more information about adenocarcinoma of the lung pathogenesis, click here.
- Large cell carcinoma of the lung:
- Large cell carcinoma of the lung arises from large polygonal and anaplastic cells.
- It is difficult to differentiate large cell carcinoma from other types of non small cell lung cancer.
- Large cell carcinoma of the lung usually occurs in a peripheral location within the lung.
- For more information about large cell carcinoma of the lung pathogenesis, click here.
- Squamous cell carcinoma of the lung:[3]
- Squamous cell carcinoma of the lung arises from bronchial epithelial cell damage, commonly caused by smoking.
- Squamous cell carcinoma usually occurs in a central location within the lung.
- For more information about squamous cell carcinoma of the lung pathogenesis, click here.
Genetics
Development of non-small cell lung cancer is the result of multiple genetic mutations. Genetic mutations also play an important role in the treatment selection for non small cell lung cancer.[4]
- The table below describes the genes involved in the pathogenesis of non small cell lung cancer.
| Genes | Presence in non small cell-lung cancers |
|---|---|
| EGFR |
|
| KRAS |
|
| ALK |
|
| HER2 |
|
| BRAF |
|
| ROS-1 |
|
Associated Conditions
Other conditions associated with non-small cell lung cancer, include:
- Genetic conditions
- Li–Fraumeni syndrome[5]
- Von Hippel-Lindau disease [6]
- Infections
Gross Pathology
On gross pathology, findings will depend on the histological subtype of non-small cell lung cancer.
- Adenocarcinoma of the lung:[2][9]
- Spherical tumor with well-defined borders
- Homogeneous gray-white cut surface
- Involvement of the thoracic wall
- Usually found in the peripheral lung
- For more information on the gross pathological findings of adenocarcinoma of the lung, click here.
- Large cell carcinoma of the lung:[10]
- Well-defined borders
- Resemblance to gross findings in adenocarcinoma
- No signs of anthracosis
- Involvement of the thoracic wall
- For more information on the gross pathological finding of large cell carcinoma of the lung, click here.
- Squamous cell carcinoma of the lung:[11]
- Lung mass
- Usually centrally located
- Associated with a large airway
- Usually have a central cavitation
- For more information on the gross pathological finding of squamous cell carcinoma of the lung, click here.
Microscopic Pathology
On microscopic pathology, findings will depend on the histological type of non-small cell lung cancer.
- Adenocarcinoma of the lung:[12]
- Nuclear atypia
- Eccentrically placed nuclei
- Abundant cytoplasm with mucin vacuoles
- Often conspicuous nucleoli
- Lack of intercellular bridges
- Different patterns, include: acinar, lepidic, micropapillary, papillary, and solid
- For more information on microscopic pathological findings of adenocarcinoma of the lung, click here.
- Large cell carcinoma of the lung:[10]
- Large polygonal cells and anaplastic cells
- No squamous or glandular differentiation
- Moderately abundant cytoplasm
- Vesicular nuclei, prominent nucleoli
- For more information on microscopic pathological findings of large cell carcinoma of the lung, click here.
- Squamous cell carcinoma of the lung:[13]
- Central nucleus
- Dense appearing cytoplasm, usually eosinophilic
- Small nucleolus
- Intercellular bridges (classic feature)
- For more information on microscopic pathological findings of squamous cell carcinoma of the lung, click here.
References
- ↑ Miller YE (2005). "Pathogenesis of lung cancer: 100 year report". Am. J. Respir. Cell Mol. Biol. 33 (3): 216–23. doi:10.1165/rcmb.2005-0158OE. PMC 2715312. PMID 16107574.
- ↑ 2.0 2.1 Thunnissen E (December 2012). "Pulmonary adenocarcinoma histology". Transl Lung Cancer Res. 1 (4): 276–9. doi:10.3978/j.issn.2218-6751.2012.10.11. PMC 4367552. PMID 25806193.
- ↑ Suarez E, Knollmann-Ritschel B (2017). "Squamous Cell Carcinoma of the Lung". Acad Pathol. 4: 2374289517705950. doi:10.1177/2374289517705950. PMC 5528918. PMID 28815199. Vancouver style error: initials (help)
- ↑ Capelozzi VL (2009). "Role of immunohistochemistry in the diagnosis of lung cancer". J Bras Pneumol. 35 (4): 375–82. PMID 19466276.
- ↑ Caron, Olivier; Frebourg, Thierry; Benusiglio, Patrick R.; Foulon, Stéphanie; Brugières, Laurence (2017). "Lung Adenocarcinoma as Part of the Li-Fraumeni Syndrome Spectrum". JAMA Oncology. 3 (12): 1736. doi:10.1001/jamaoncol.2017.1358. ISSN 2374-2437.
- ↑ Sekido Y, Bader S, Latif F, Gnarra JR, Gazdar AF, Linehan WM, Zbar B, Lerman MI, Minna JD (June 1994). "Molecular analysis of the von Hippel-Lindau disease tumor suppressor gene in human lung cancer cell lines". Oncogene. 9 (6): 1599–604. PMID 8183553.
- ↑ Liang H, Pan Z, Cai X, Wang W, Guo C, He J, Chen Y, Liu Z, Wang B, He J, Liang W (June 2018). "The association between human papillomavirus presence and epidermal growth factor receptor mutations in Asian patients with non-small cell lung cancer". Transl Lung Cancer Res. 7 (3): 397–403. doi:10.21037/tlcr.2018.03.16. PMC 6037964. PMID 30050777.
- ↑ Skowroński M, Iwanik K, Halicka A, Barinow-Wojewódzki A (2015). "Squamous cell lung cancer in a male with pulmonary tuberculosis". Pneumonol Alergol Pol. 83 (4): 298–302. doi:10.5603/PiAP.2015.0049. PMID 26166791.
- ↑ Suarez E, Knollmann-Ritschel B (2017). "Squamous Cell Carcinoma of the Lung". Acad Pathol. 4: 2374289517705950. doi:10.1177/2374289517705950. PMC 5528918. PMID 28815199. Vancouver style error: initials (help)
- ↑ 10.0 10.1 Miller YE (2005). "Pathogenesis of lung cancer: 100 year report". Am. J. Respir. Cell Mol. Biol. 33 (3): 216–23. doi:10.1165/rcmb.2005-0158OE. PMC 2715312. PMID 16107574.
- ↑ Suarez E, Knollmann-Ritschel B (2017). "Squamous Cell Carcinoma of the Lung". Acad Pathol. 4: 2374289517705950. doi:10.1177/2374289517705950. PMC 5528918. PMID 28815199. Vancouver style error: initials (help)
- ↑ Suarez E, Knollmann-Ritschel B (2017). "Squamous Cell Carcinoma of the Lung". Acad Pathol. 4: 2374289517705950. doi:10.1177/2374289517705950. PMC 5528918. PMID 28815199. Vancouver style error: initials (help)
- ↑ Suarez E, Knollmann-Ritschel B (2017). "Squamous Cell Carcinoma of the Lung". Acad Pathol. 4: 2374289517705950. doi:10.1177/2374289517705950. PMC 5528918. PMID 28815199. Vancouver style error: initials (help)