Non small cell lung cancer pathophysiology

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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.

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.
• 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, and lung parenchymal), 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.
• 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.
• Genes involved in the pathogenesis of non small cell lung cancer include:

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

Non small cell lung cancer is associated with other conditions that include:

Gross Pathology

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

• Lung adenocarcinoma is usually found in the peripheral lung
• Spherical tumor with well-defined borders
• Homogeneous gray-white cut surface
• Involvement of the thoracic wall

• Large cell lung cancer gross pathology findings, include:
• Indistinguishable from lung adenocarincoma
• Squamous cell lung cancer gross pathology findings, include:

Microscopic Pathology

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

References

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