Squamous cell carcinoma of the lung pathophysiology: Difference between revisions

Jump to navigation Jump to search
VisualWikitext
No edit summary
No edit summary
 
(12 intermediate revisions by one other user not shown)
Line 5: Line 5:
==Overview==
==Overview==


Squamous cell carcinoma of the lung arises from the [[epithelial]] cells of the lung of the central [[bronchi]] to terminal [[alveoli]], which are normally involved in the protection of the airways. The pathological irritation caused by cigarette smoke causes the mucus-secreting ciliated pseudostratified columnar respiratory epithelial cells that line the airways to be replaced by stratified squamous epithelium. Squamous cell carcinoma of the lung has a central location and usually appears as a hiliar or perihiliar mass. Squamous cell carcinoma of the lung is a rapidly growing cancer which may metastasize to various organs of the body. Genes involved in the pathogenesis of squamous cell carcinoma include several oncogenes, such as: [[EGFR|''EGFR'']]'', EML-4, [[KRAS]], [[HER2/neu|HER2]],'' and [[ALK-1|''ALK'']].<ref name="pmid22722794">{{cite journal |vauthors=Heist RS, Sequist LV, Engelman JA |title=Genetic changes in squamous cell lung cancer: a review |journal=J Thorac Oncol |volume=7 |issue=5 |pages=924–33 |year=2012 |pmid=22722794 |pmc=3404741 |doi=10.1097/JTO.0b013e31824cc334 |url=}}</ref> On gross pathology, findings include central necrosis, cavitation, and invasion of peribronchial soft tissue. On microscopic histopathological analysis squamous cell carcinoma of the lung demonstrate large polygonal malignant cells containing keratin and intercellular bridges. On inmunohistochemistry, findings associated with squamous cell carcinoma of the lung include the presence of [[p53]] and high-molecular weight keratins for squamous cell carcinoma. Other squamous immunomarkers, include: CK5/6, CEA, 34BE12, TTF-1, and CK7.
Squamous cell carcinoma of the lung arises from the [[epithelial]] cells of the lung of the central [[bronchi]] to terminal [[alveoli]], which are normally involved in the protection of the airways. The pathological irritation caused by cigarette smoke causes the mucus-secreting ciliated pseudostratified columnar respiratory epithelial cells that line the airways to be replaced by stratified squamous epithelium. Squamous cell carcinoma of the lung has a central location and usually appears as a hiliar or perihiliar mass. Squamous cell carcinoma of the lung is a rapidly growing cancer which may metastasize to various organs of the body. Genes involved in the pathogenesis of squamous cell carcinoma include several oncogenes, such as: [[EGFR|''EGFR'']]'', EML-4, [[KRAS]], [[HER2/neu|HER2]],'' and [[ALK-1|''ALK'']]. On gross pathology, findings include central necrosis, cavitation, and invasion of peribronchial soft tissue. On microscopic histopathological analysis squamous cell carcinoma of the lung demonstrate large polygonal malignant cells containing keratin and intercellular bridges. On immunohistochemistry, findings associated with squamous cell carcinoma of the lung include the presence of [[p53]] and high-molecular weight keratins for squamous cell carcinoma. Other squamous immunomarkers, include: CK5/6, CEA, 34BE12, TTF-1, and CK7.


==Pathogenesis==
==Pathophysiology==
===Lung Cancer Pathogenesis===
*Lung cancer [[pathogenesis]] can be understood with the help of following [[hypothesis]].<ref name="KanwalDing2017">{{cite journal|last1=Kanwal|first1=Madiha|last2=Ding|first2=Xiao-Ji|last3=Cao|first3=Yi|title=Familial risk for lung cancer|journal=Oncology Letters|volume=13|issue=2|year=2017|pages=535–542|issn=1792-1074|doi=10.3892/ol.2016.5518}}</ref><ref name="KadaraScheet2016">{{cite journal|last1=Kadara|first1=H.|last2=Scheet|first2=P.|last3=Wistuba|first3=I. I.|last4=Spira|first4=A. E.|title=Early Events in the Molecular Pathogenesis of Lung Cancer|journal=Cancer Prevention Research|volume=9|issue=7|year=2016|pages=518–527|issn=1940-6207|doi=10.1158/1940-6207.CAPR-15-0400}}</ref><ref name="RasoWistuba2007">{{cite journal|last1=Raso|first1=Maria Gabriela|last2=Wistuba|first2=Ignacio I.|title=Molecular Pathogenesis of Early-Stage Non-small Cell Lung Cancer and a Proposal for Tissue Banking to Facilitate Identification of New Biomarkers|journal=Journal of Thoracic Oncology|volume=2|issue=7|year=2007|pages=S128–S135|issn=15560864|doi=10.1097/JTO.0b013e318074fe42}}</ref>
*'''Familial lung cancer''':
**[[Chromosome 6 (human)|6q23–25]] [[Locus (genetics)|locus]] has been identified as a [[Susceptible individual|susceptibility]] [[gene]] for familial lung cancer.
 
*'''Multistep tumorigenesis''':
**[[Tumor|Tumors]] of organs such as [[Skin cancer|skin]], [[lung]] and [[Colorectal cancer|colon]] are developed through a process called [[Tumorigenesis|multistep tumorigenesis]].
**As with other epithelial malignancies, lung cancers are believed to arise from preneoplastic or precursor lesions in the respiratory mucosa.
**[[Tumorigenesis|Multistep tumorigenesis]] is development of [[tumor]] through a series of progressive [[Pathological|pathologic]] events such as [[Precancerous|preneoplastic]] or [[Precursor|precursor lesions]] with corresponding [[genetic]] and [[Epigenetic|epigenetic aberrations]].
**[[Hyperplasia]], [[squamous metaplasia]], [[Dysplasia|squamous dysplasia]], and [[Carcinoma in situ|carcinoma ''in situ'' (CIS)]] comprise changes in the [[Bronchus|large airways]] that precede or accompany [[Squamous cell carcinoma of the lung|invasive squamous cell carcinoma of the lung]].<ref name="pmid18039118">{{cite journal |vauthors=Wistuba II, Gazdar AF |title=Lung cancer preneoplasia |journal=Annu Rev Pathol |volume=1 |issue= |pages=331–48 |date=2006 |pmid=18039118 |doi=10.1146/annurev.pathol.1.110304.100103 |url=}}</ref>
**Multistep [[tumorigenesis]] explains [[pathogenesis]] of centrally located [[squamous cell carcinoma of the lung]] very well but fails to explain [[pathogenesis]] of [[Large cell carcinoma of the lung|large cell lung carcinomas]], [[Adenocarcinoma of the lung|lung adenocarcinomas]], and [[small cell lung cancer]].
 
*'''Accumulation of molecular abnormalities:'''
**Another theory for [[pathogenesis]] of lung cancer is the accumulation of [[Molecule|molecular]] abnormalities beyond a certain threshold point, rather than the sequence of alterations.
**There are no known [[Precancerous|preneoplastic lesions]] for the most common type of [[Carcinoid syndrome|neuroendocrine lung tumors]], [[Small cell lung cancer|small cell carcinoma of the lung]],
**[[Adenocarcinoma of the lung pathophysiology|Atypical adenomatous hyperplasia (AAH)]] is the only sequence of [[Morphology (biology)|morphologic]] change identified leading to the development of [[Adenocarcinoma of the lung|invasive adenocarcinoma of the lung.]]
*[[Pathogenesis]] of lung cancer is thought to be result of both due to stepwise, sequence-specific and multistage [[Molecular pathology|molecular pathogenesis]] and due to accumulation and combination of [[Genetics|genetic]] and [[Epigenetics|epigenetic]] abnormalities.
===Field of Injury and Field Cancerization===
*[[Premalignant condition|Preneoplastic lung lesions]] frequently extend throughout the [[respiratory epithelium]], indicating a field effect in which much of the [[respiratory epithelium]] has been [[Mutagen|mutagenized]], presumably from exposure to tobacco-related carcinogens.<ref name="DevarakondaMorgensztern2015">{{cite journal|last1=Devarakonda|first1=Siddhartha|last2=Morgensztern|first2=Daniel|last3=Govindan|first3=Ramaswamy|title=Genomic alterations in lung adenocarcinoma|journal=The Lancet Oncology|volume=16|issue=7|year=2015|pages=e342–e351|issn=14702045|doi=10.1016/S1470-2045(15)00077-7}}</ref><ref name="pmid27006378">{{cite journal |vauthors=Kadara H, Scheet P, Wistuba II, Spira AE |title=Early Events in the Molecular Pathogenesis of Lung Cancer |journal=Cancer Prev Res (Phila) |volume=9 |issue=7 |pages=518–27 |date=July 2016 |pmid=27006378 |doi=10.1158/1940-6207.CAPR-15-0400 |url=}}</ref><ref name="AuerbachStout1961">{{cite journal|last1=Auerbach|first1=Oscar|last2=Stout|first2=A. P.|last3=Hammond|first3=E. Cuyler|last4=Garfinkel|first4=Lawrence|title=Changes in Bronchial Epithelium in Relation to Cigarette Smoking and in Relation to Lung Cancer|journal=New England Journal of Medicine|volume=265|issue=6|year=1961|pages=253–267|issn=0028-4793|doi=10.1056/NEJM196108102650601}}</ref>
*[[Epithelium|Epithelial cells]] lining the entire [[respiratory tract]] that have been exposed to [[smoking]] show [[Molecular pathology|molecular alterations]] that may signify the onset of lung cancers, a [[paradigm]] known as the "airway field of injury”.
*
*[[Premalignant]] [[airway]] fields in the molecular pathogenesis of lung cancer:
**[[Smoking]] induces widespread [[Molecular pathology|molecular alterations]], such as [[gene expression]] changes in exposed [[Epithelium|epithelia]] throughout the [[Respiratory tract|respiratory tract.]]
**The [[airway]] field of injury can be seen in smokers with or without lung cancer and is highly relevant for the identification of [[Tumor marker|markers]] for [[Minimally invasive adenocarcinoma of the lung|minimally invasive]] and early detection of lung cancer.
**The adjacent [[airway]] field of [[Oncogenesis|carcinoma]] represents the field in normal appearing [[Airway|airways]] adjacent to [[lung]] [[Tumor|tumors]].
**It has been suggested that in this adjacent field of [[tumor]], there is closer [[Molecular pathology|molecular genealogy]] between lung cancers and [[Airway|airways]] that are in closest proximity to the [[Tumor|tumors]] compared with [[Airway|airways]] that are more distant from the [[tumors]].
**The progression of the molecular airway field of injury to [[Precancerous|preneoplasia]] and lung malignancy is still not clear.
**[[Molecular pathology|Molecular changes]] involved in the development of the [[airway]] field of injury and changes mediating progression of this field to [[lung]] [[Precancerous|preneoplasia]] may help the identification of early [[Marker|markers]] for lung cancer detection and [[Chemoprophylaxis|chemoprevention]].
 
=== Pathogenesis ===
*Squamous cell carcinoma of the lung arises from bronchial epithelial cell damage (usually related with active smoking).  
*Squamous cell carcinoma of the lung arises from bronchial epithelial cell damage (usually related with active smoking).  
*Pathological irritation caused by cigarette smoke causes the mucus-secreting ciliated [[Pseudostratified epithelium|pseudostratified columnar respiratory epithelial cells]] that line the airways to be replaced by stratified squamous epithelium.
*Basal cells in the large airways exhibit pluripotent capacity following cigarette smoke exposure.
*These pluripotent basal cells give rise to metaplastic and dysplastic squamous cells, which in turn function as precursors of squamous cell carcinomas.
*
*
*The [[squamous metaplasia]] is then followed by epithelial dysplasia, which consists of an expansion of immature cells with a corresponding decrease in the number and location of mature cells.
*The [[squamous metaplasia]] is then followed by epithelial dysplasia, which consists of an expansion of immature cells with a corresponding decrease in the number and location of mature cells.
*[[Dysplasia]] is often indicative of an early neoplastic process in squamous cell carcinoma of the lung.
*[[Dysplasia]] is often indicative of an early neoplastic process in squamous cell carcinoma of the lung.
*Squamous cell carcinoma of the lung has a central location and usually appears as a hiliar or perihiliar mass.
*Squamous cell carcinoma of the lung has a central location and usually appears as a hiliar or peri-hilar mass.
*Squamous cell carcinoma of the lung is a rapidly growing cancer which may metastasize to various organs of the body.
*Squamous cell carcinoma of the lung is a rapidly growing cancer which may metastasize to various organs of the body.
*Basaloid lung cell carcinoma is the most aggressive subtype of squamous cell carcinoma of the lung.
*Basaloid lung cell carcinoma is the most aggressive subtype of squamous cell carcinoma of the lung.
*
*
*
==Genetics==


===Molecular Pathogenesis===
==== Molecular Pathogenesis of Squamous Cell Carcinoma of the Lung ====
* Development of squamous cell carcinoma of the lung is the result of multiple [[genetic mutation]]s.<ref name="pmid22722794">{{cite journal |vauthors=Heist RS, Sequist LV, Engelman JA |title=Genetic changes in squamous cell lung cancer: a review |journal=J Thorac Oncol |volume=7 |issue=5 |pages=924–33 |year=2012 |pmid=22722794 |pmc=3404741 |doi=10.1097/JTO.0b013e31824cc334 |url=}}</ref>
* Genetic mutations play an important role in the treatment selection for squamous cell carcinoma of the lung.
* Squamous cell carcinoma of the lung is a [[diploid]] or hyperdiploid [[aneuploid]] neoplasm with mean chromosome numbers in the triploid range.<ref name="pmid24488911">{{cite journal |vauthors=Shi WY, Liu KD, Xu SG, Zhang JT, Yu LL, Xu KQ, Zhang TF |title=Gene expression analysis of lung cancer |journal=Eur Rev Med Pharmacol Sci |volume=18 |issue=2 |pages=217–28 |year=2014 |pmid=24488911 |doi= |url=}}</ref>
* Squamous cell carcinoma of the lung is a [[diploid]] or hyperdiploid [[aneuploid]] neoplasm with mean chromosome numbers in the triploid range.<ref name="pmid24488911">{{cite journal |vauthors=Shi WY, Liu KD, Xu SG, Zhang JT, Yu LL, Xu KQ, Zhang TF |title=Gene expression analysis of lung cancer |journal=Eur Rev Med Pharmacol Sci |volume=18 |issue=2 |pages=217–28 |year=2014 |pmid=24488911 |doi= |url=}}</ref>
* In squamous cell carcinoma of the lung, there is a multitude of alterations with amplifications of the telomeric 3q region.
*In squamous cell carcinoma of the lung, there is a multitude of alterations with amplifications of the telomeric 3q region.
* Gain of 3q24-qter is present in the majority of squamous cell carcinomas of the lung.
* Gain of 3q24-qter is present in the majority of squamous cell carcinomas of the lung.
* Disruption of normal [[p53 gene]] is frequent in squamous cell carcinoma of the lung.
* Disruption of normal [[p53 gene]] is frequent in squamous cell carcinoma of the lung.
*
==Genetics==
* Development of squamous cell carcinoma of the lung is the result of multiple [[genetic mutation]]s.
* Genetic mutations play an important role in the treatment selection for squamous cell carcinoma of the lung.
* [[Genes]] involved in the pathogenesis of squamous cell carcinoma include the following:<ref name="pmid24488911">{{cite journal |vauthors=Shi WY, Liu KD, Xu SG, Zhang JT, Yu LL, Xu KQ, Zhang TF |title=Gene expression analysis of lung cancer |journal=Eur Rev Med Pharmacol Sci |volume=18 |issue=2 |pages=217–28 |year=2014 |pmid=24488911 |doi= |url=}}</ref>
* [[Genes]] involved in the pathogenesis of squamous cell carcinoma include the following:<ref name="pmid24488911">{{cite journal |vauthors=Shi WY, Liu KD, Xu SG, Zhang JT, Yu LL, Xu KQ, Zhang TF |title=Gene expression analysis of lung cancer |journal=Eur Rev Med Pharmacol Sci |volume=18 |issue=2 |pages=217–28 |year=2014 |pmid=24488911 |doi= |url=}}</ref>
:*[[EGFR|''EGFR'']]
**[[EGFR|''EGFR'']]
::*84% of squamous cell carcinomas of the lung are positive for ''[[EGFR]]''
*** 84% of squamous cell carcinomas of the lung are positive for ''[[EGFR]]''
:*''EML-4''  
** ''EML-4''
:*[[ALK-1|''ALK'']]  
** [[ALK-1|''ALK'']]
:*[[KRAS|''KRAS'']]  
** [[KRAS|''KRAS'']]
::*30% of squamous cell carcinomas of the lung are positive for ''[[KRAS]]''
*** 30% of squamous cell carcinomas of the lung are positive for ''[[KRAS]]''
:*[[HER2/neu|''HER2'']]  
** [[HER2/neu|''HER2'']]
::*Rare in squamous cell carcinomas of the lung
*** Rare in squamous cell carcinomas of the lung
 
==Associated Conditions==
==Associated Conditions==


Line 42: Line 77:


==Gross Pathology==
==Gross Pathology==
{| align="right"
 
|
[[Image:Bronchial cancer.jpeg|x200px|thumb|Gross pathology: Bronchial squamous lung cell cancer By John Hayman [Public domain], (Image source: [https://commons.wikimedia.org/wiki/File%3ACa_bronchus.jpg Wikimedia Commons])]]
|}
*On gross pathology, findings associated with squamous cell carcinoma of the lung include:<ref name="pathology">Non small cell lung cancer. Libre Pathology. http://librepathology.org/wiki/Non-small_cell_lung_carcinoma Accessed on February 22, 2016 </ref>
*On gross pathology, findings associated with squamous cell carcinoma of the lung include:<ref name="pathology">Non small cell lung cancer. Libre Pathology. http://librepathology.org/wiki/Non-small_cell_lung_carcinoma Accessed on February 22, 2016 </ref>
:*Lung mas that is usually centrally located
:*Lung mas that is usually centrally located
Line 52: Line 84:
:*[[Cavitation|Central cavitation]]
:*[[Cavitation|Central cavitation]]
==Microscopic Pathology==
==Microscopic Pathology==
{| align="right"
 
|
[[Image:Squamous cell mircopathology2.jpeg|x200px|thumb| Micropathology: Squamous cell carcinoma of the lung. H&E stain, By Nephron [https://commons.wikimedia.org/wiki/File%3ALung_squamous_carcinoma_--_high_mag.jpg Wikimedia Commons]]]
|}
*On microscopic pathology, findings associated with squamous cell carcinoma of the lung include:<ref name="pathology">Non small cell lung cancer. Libre Pathology. http://librepathology.org/wiki/Non-small_cell_lung_carcinoma Accessed on February 22, 2016 </ref>
*On microscopic pathology, findings associated with squamous cell carcinoma of the lung include:<ref name="pathology">Non small cell lung cancer. Libre Pathology. http://librepathology.org/wiki/Non-small_cell_lung_carcinoma Accessed on February 22, 2016 </ref>
:*Central [[Cell nucleus|nucleus]]
**Central [[Cell nucleus|nucleus]]
:*Dense appearing [[cytoplasm]], usually [[eosinophilic]]
**Dense appearing [[cytoplasm]], usually [[eosinophilic]]
:*Small [[nucleolus]]
**Small [[nucleolus]]
:*'''Intracellular bridges''' (classic feature)
**Intracellular bridges (classic feature)
 
*The IASLC/ATS/ERS lung adenocarcinoma [[Histology|histologic]] [[classification]] system was proposed in the ''Journal of Thoracic Oncology'' in 2011.<ref>{{cite journal|doi=10.3978/j.issn.2072-1439.2014.09.13}}</ref>
*On inmunohistochemistry, findings associated with squamous cell carcinoma of the lung include:<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>
**'''Keratinizing squamous cell carcinoma:'''
:*Presence of p63 and high-molecular weight [[Keratin|keratins]] for squamous cell carcinoma
*** Tumor budding, single cell invasion, and large nuclei.
:*Other squamous immunomarkers include CK5/6, [[CEA]], 34BE12, [[Thyroid transcription factor-1|TTF-1]], and CK7
*** Tumor budding, or the presence of small tumor nests.
:*Differentiation of squamous cell carcinoma of the lung from adenocarcinoma on biopsy is vital as response to cytotoxic and biological agents will greatly differ
*** A large nucleus was defined as a diameter greater than that of four small lymphocytes.
 
****
** '''Nonkeratinizing squamous cell carcinoma'''
***
** '''Basaloid squamous cell carcinoma'''
** '''Preinvasive lesion'''
** '''Squamous cell carcinoma in situ'''
===Immunohistochemistry===
* Findings associated with squamous cell carcinoma of the lung include:<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>
* Presence of p63 and high-molecular weight [[Keratin|keratins]] for squamous cell carcinoma.
* Other squamous immunomarkers include CK5/6, [[CEA]], 34BE12, [[Thyroid transcription factor-1|TTF-1]], and CK7.
* Differentiation of squamous cell carcinoma of the lung from adenocarcinoma on biopsy is vital as response to cytotoxic and biological agents will greatly differ.


==References==
==References==

Latest revision as of 19:34, 17 October 2019

Squamous Cell Carcinoma of the Lung Microchapters

Home

Patient Information

Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating Squamous Cell Carcinoma of the Lung 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 scan

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

Squamous cell carcinoma of the lung pathophysiology On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides

Images

American Roentgen Ray Society Images of Squamous cell carcinoma of the lung pathophysiology

All Images
X-rays
Echo & Ultrasound
CT Images
MRI

Ongoing Trials at Clinical Trials.gov

US National Guidelines Clearinghouse

NICE Guidance

FDA on Squamous cell carcinoma of the lung pathophysiology

CDC on Squamous cell carcinoma of the lung pathophysiology

Squamous cell carcinoma of the lung pathophysiology in the news

Blogs on Squamous cell carcinoma of the lung pathophysiology

Directions to Hospitals Treating Squamous cell carcinoma of the lung

Risk calculators and risk factors for Squamous cell carcinoma of the lung pathophysiology

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

Squamous cell carcinoma of the lung arises from the epithelial cells of the lung of the central bronchi to terminal alveoli, which are normally involved in the protection of the airways. The pathological irritation caused by cigarette smoke causes the mucus-secreting ciliated pseudostratified columnar respiratory epithelial cells that line the airways to be replaced by stratified squamous epithelium. Squamous cell carcinoma of the lung has a central location and usually appears as a hiliar or perihiliar mass. Squamous cell carcinoma of the lung is a rapidly growing cancer which may metastasize to various organs of the body. Genes involved in the pathogenesis of squamous cell carcinoma include several oncogenes, such as: EGFR, EML-4, KRAS, HER2, and ALK. On gross pathology, findings include central necrosis, cavitation, and invasion of peribronchial soft tissue. On microscopic histopathological analysis squamous cell carcinoma of the lung demonstrate large polygonal malignant cells containing keratin and intercellular bridges. On immunohistochemistry, findings associated with squamous cell carcinoma of the lung include the presence of p53 and high-molecular weight keratins for squamous cell carcinoma. Other squamous immunomarkers, include: CK5/6, CEA, 34BE12, TTF-1, and CK7.

Pathophysiology

Lung Cancer Pathogenesis

Field of Injury and Field Cancerization

Pathogenesis

  • Squamous cell carcinoma of the lung arises from bronchial epithelial cell damage (usually related with active smoking).
  • Basal cells in the large airways exhibit pluripotent capacity following cigarette smoke exposure.
  • These pluripotent basal cells give rise to metaplastic and dysplastic squamous cells, which in turn function as precursors of squamous cell carcinomas.
  • The squamous metaplasia is then followed by epithelial dysplasia, which consists of an expansion of immature cells with a corresponding decrease in the number and location of mature cells.
  • Dysplasia is often indicative of an early neoplastic process in squamous cell carcinoma of the lung.
  • Squamous cell carcinoma of the lung has a central location and usually appears as a hiliar or peri-hilar mass.
  • Squamous cell carcinoma of the lung is a rapidly growing cancer which may metastasize to various organs of the body.
  • Basaloid lung cell carcinoma is the most aggressive subtype of squamous cell carcinoma of the lung.

Genetics

Molecular Pathogenesis of Squamous Cell Carcinoma of the Lung

  • Development of squamous cell carcinoma of the lung is the result of multiple genetic mutations.[8]
  • Genetic mutations play an important role in the treatment selection for squamous cell carcinoma of the lung.
  • Squamous cell carcinoma of the lung is a diploid or hyperdiploid aneuploid neoplasm with mean chromosome numbers in the triploid range.[9]
  • In squamous cell carcinoma of the lung, there is a multitude of alterations with amplifications of the telomeric 3q region.
  • Gain of 3q24-qter is present in the majority of squamous cell carcinomas of the lung.
  • Disruption of normal p53 gene is frequent in squamous cell carcinoma of the lung.
  • Genes involved in the pathogenesis of squamous cell carcinoma include the following:[9]
    • EGFR
      • 84% of squamous cell carcinomas of the lung are positive for EGFR
    • EML-4
    • ALK
    • KRAS
      • 30% of squamous cell carcinomas of the lung are positive for KRAS
    • HER2
      • Rare in squamous cell carcinomas of the lung

Associated Conditions

  • Conditions associated with squamous cell carcinoma of the lung include:[9]

Gross Pathology

  • On gross pathology, findings associated with squamous cell carcinoma of the lung include:[10]
  • Lung mas that is usually centrally located
  • Invasion of peribronchial soft-tissue, lymph nodes, and lung parenchyma
  • Large mass causing compression of pulmonary artery and vein
  • Central cavitation

Microscopic Pathology

  • On microscopic pathology, findings associated with squamous cell carcinoma of the lung include:[10]
  • The IASLC/ATS/ERS lung adenocarcinoma histologic classification system was proposed in the Journal of Thoracic Oncology in 2011.[11]
    • Keratinizing squamous cell carcinoma:
      • Tumor budding, single cell invasion, and large nuclei.
      • Tumor budding, or the presence of small tumor nests.
      • A large nucleus was defined as a diameter greater than that of four small lymphocytes.
    • Nonkeratinizing squamous cell carcinoma
    • Basaloid squamous cell carcinoma
    • Preinvasive lesion
    • Squamous cell carcinoma in situ

Immunohistochemistry

  • Findings associated with squamous cell carcinoma of the lung include:[12]
  • Presence of p63 and high-molecular weight keratins for squamous cell carcinoma.
  • Other squamous immunomarkers include CK5/6, CEA, 34BE12, TTF-1, and CK7.
  • Differentiation of squamous cell carcinoma of the lung from adenocarcinoma on biopsy is vital as response to cytotoxic and biological agents will greatly differ.

References

  1. ↑ Kanwal, Madiha; Ding, Xiao-Ji; Cao, Yi (2017). "Familial risk for lung cancer". Oncology Letters. 13 (2): 535–542. doi:10.3892/ol.2016.5518. ISSN 1792-1074.
  2. ↑ Kadara, H.; Scheet, P.; Wistuba, I. I.; Spira, A. E. (2016). "Early Events in the Molecular Pathogenesis of Lung Cancer". Cancer Prevention Research. 9 (7): 518–527. doi:10.1158/1940-6207.CAPR-15-0400. ISSN 1940-6207.
  3. ↑ Raso, Maria Gabriela; Wistuba, Ignacio I. (2007). "Molecular Pathogenesis of Early-Stage Non-small Cell Lung Cancer and a Proposal for Tissue Banking to Facilitate Identification of New Biomarkers". Journal of Thoracic Oncology. 2 (7): S128–S135. doi:10.1097/JTO.0b013e318074fe42. ISSN 1556-0864.
  4. ↑ Wistuba II, Gazdar AF (2006). "Lung cancer preneoplasia". Annu Rev Pathol. 1: 331–48. doi:10.1146/annurev.pathol.1.110304.100103. PMID 18039118.
  5. ↑ Devarakonda, Siddhartha; Morgensztern, Daniel; Govindan, Ramaswamy (2015). "Genomic alterations in lung adenocarcinoma". The Lancet Oncology. 16 (7): e342–e351. doi:10.1016/S1470-2045(15)00077-7. ISSN 1470-2045.
  6. ↑ Kadara H, Scheet P, Wistuba II, Spira AE (July 2016). "Early Events in the Molecular Pathogenesis of Lung Cancer". Cancer Prev Res (Phila). 9 (7): 518–27. doi:10.1158/1940-6207.CAPR-15-0400. PMID 27006378.
  7. ↑ Auerbach, Oscar; Stout, A. P.; Hammond, E. Cuyler; Garfinkel, Lawrence (1961). "Changes in Bronchial Epithelium in Relation to Cigarette Smoking and in Relation to Lung Cancer". New England Journal of Medicine. 265 (6): 253–267. doi:10.1056/NEJM196108102650601. ISSN 0028-4793.
  8. ↑ Heist RS, Sequist LV, Engelman JA (2012). "Genetic changes in squamous cell lung cancer: a review". J Thorac Oncol. 7 (5): 924–33. doi:10.1097/JTO.0b013e31824cc334. PMC 3404741. PMID 22722794.
  9. ↑ 9.0 9.1 9.2 Shi WY, Liu KD, Xu SG, Zhang JT, Yu LL, Xu KQ, Zhang TF (2014). "Gene expression analysis of lung cancer". Eur Rev Med Pharmacol Sci. 18 (2): 217–28. PMID 24488911.
  10. ↑ 10.0 10.1 Non small cell lung cancer. Libre Pathology. http://librepathology.org/wiki/Non-small_cell_lung_carcinoma Accessed on February 22, 2016
  11. ↑ . doi:10.3978/j.issn.2072-1439.2014.09.13. Missing or empty |title= (help)
  12. ↑ 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.


Template:WikiDoc Sources

Retrieved from "https://www.wikidoc.org/index.php?title=Squamous_cell_carcinoma_of_the_lung_pathophysiology&oldid=1584881"