Non small cell lung cancer pathophysiology

	Non Small Cell Lung Cancer Microchapters
Home
Patient Information
Overview
Historical Perspective
Classification
Pathophysiology
Causes
Differentiating Non Small Cell Lung 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
CT Scan
MRI
Ultrasound
Other Imaging Findings
Other Diagnostic Studies
Treatment
Management Approach Stage I Stage II Stage III Stage IV Metastatic Cancer
Medical Therapy Chemotherapy Radiation Therapy
Surgery
Primary Prevention
Secondary Prevention
Cost-Effectiveness of Therapy
Future or Investigational Therapies
Case Studies
Case #1
Non small cell lung cancer pathophysiology On the Web
Most recent articles
Most cited articles
Review articles
CME Programs
Powerpoint slides
Images
American Roentgen Ray Society Images of Non small cell lung 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 Non small cell lung cancer pathophysiology
CDC on Non small cell lung cancer pathophysiology
Non small cell lung cancer pathophysiology in the news
Blogs on Non small cell lung cancer pathophysiology
Directions to Hospitals Treating Non small cell carcinoma of the lung
Risk calculators and risk factors for Non small cell lung cancer pathophysiology

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Maria Fernanda Villarreal, M.D. [2]

Overview

Non-small cell lung cancer 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. 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. On gross pathology, findings will depend on the histological type. On microscopic histopathological analysis non-small cell lung cancer demonstrate large cells with abundant cytoplasm and no stippled chromatin.^[1]

Pathogenesis

The pathogenesis of non-small cell lung cancer will depend on the type of histological subtype of lung cancer: lung adenocarcinoma, lung large cell carcinoma, and squamous cell lung carcinoma.^[1]
Non-small cell lung cancer 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.
Lung adenocarcinoma arises from the bronchial mucosal glands of the lung (main, lobar, segmental bronchi, or lung parenchyma), which are normally involved in decreasing bacterial 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 lung adenocarcinoma pathogenesis, see here
Squamous lung cell carcinoma arises from bronchial epithelial cell damage (related with active smoking). Squamous cell carcinoma usually occurs in a central location within the lung. For more information about squamous lung cell carcinoma pathogenesis, see here
Large cell carcinoma of the lung arises from large polygonal and anaplastic cells, hard to differentiate from other types of non small cell lung cancer. Large cell carcinoma usually occurs in a peripheral location within the lung.For more information about large cell carcinoma pathogenesis, see here
Non-small cell lung cancer is an invasive and rapidly growing cancer which may metastasize to different organs of the body.

Genetics

Development of non-small cell lung cancer is the result of multiple genetic mutations.
Genetic mutations play an important role in the treatment selection for non small cell lung cancer.
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	EGFR mutations are present in approximately 10% to 15% of all non-small cell lung cancers
KRAS	Mutations are present in approximately 30% of pulmonary adenocarcinomas Mutations are present in approximately 5% of pulmonary squamous cell carcinomas Associated with carcinomas with mucinous histology
ALK	Mutations are present in approximately 5% of all non-small cell lung cancers
HER2	Mutations are present in approximately 4% of adenocarcinomas
BRAF	Mutations are present in less than 2% of adenocarcinomas
ROS-1	Mutations are present in less than 2% of adenocarcinomas

Associated Conditions

Other conditions associated with non-small cell lung cancer, include:
Genetic conditions

Li–Fraumeni syndrome
Noonan syndrome

Infections

Gross Pathology

On gross pathology, findings will depend on the histological subtype of non-small cell lung cancer.
Lung adenocarcinoma gross pathology findings, include:^[2]

Spherical tumor with well-defined borders
Homogeneous gray-white cut surface
Involvement of the thoracic wall
Usually found in the peripheral lung

Large cell lung cancer gross pathology findings, include:^[2]

Well-defined borders
Resemblance to gross findings in adenocarcinoma
No signs of anthracosis
Involvement of the thoracic wall

Squamous cell lung cancer gross pathology findings, include:^[2]

Lung mass
Usually centrally located
Associated with a large airway
Usually have a central cavitation

Microscopic Pathology

On microscopic pathology, findings will depend on the histological type of non-small cell lung cancer.
Lung adenocarcinoma microscopic pathology findings, include:^[2]

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.

Large cell lung cancer microscopic pathology findings, include:^[2]

Large polygonal cells and anaplastic cells
No squamous or glandular differentiation
Moderately abundant cytoplasm
Vesicular nuclei, prominent nucleoli

Squamous cell lung cancer microscopic pathology findings, include:^[2]

Central nucleus
Dense appearing cytoplasm, usually eosinophilic
Small nucleolus
Intracellular bridges (classic feature)

On inmunohistochemistry, findings will depend on the histological type of non-small cell lung cancer.
Common inmunohistochemistry markers used for non-small cell carcinoma subtyping, include:^[2]

TTF-1 for adenocarcinoma
p63 and high-molecular weight keratins for squamous cell carcinoma
Lack of staining with neuroendocrine markers (chromogranin A, synaptophysin, and CD56)