Adenocarcinoma of the lung pathophysiology
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Adenocarcinoma of the Lung Microchapters |
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Differentiating Adenocarcinoma of the Lung from other Diseases |
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Shanshan Cen, M.D. [2]
Overview
Histopathology
Adenocarcinoma of the lung tends to stain mucin positive as it is derived from the mucus producing glands of the lungs. Similar to other adenocarcinoma, if this tumor is well differentiated (low grade) it will resemble the normal glandular structure. Poorly differentiated adenocarcinoma will not resemble the normal glands (high grade) and will be detected by seeing that they stain positive for mucin (which the glands produce).[1][2] Adenocarcinoma can also be distinguished by staining for TTF-1, a cell marker for adenocarcinoma.[3]
To reveal the adenocarcinomatous lineage of the solid variant, demonstration of intracellular mucin production may be performed. Foci of squamous metaplasia and dysplasia may be present in the epithelium proximal to adenocarcinomas, but these are not the precursor lesions for this tumor. Rather, the precursor of peripheral adenocarcinomas has been termed atypical adenomatous hyperplasia (AAH).[4] Microscopically, AAH is a well-demarcated focus of epithelial proliferation, containing cuboidal to low-columnar cells resembling club cells or type II pneumocytes.[4] These demonstrate various degrees of cytologic atypia, including hyperchromasia, pleomorphism, prominent nucleoli.[4] However, the atypia is not to the extent as seen in frank adenocarcinomas.[4] Lesions of AAH are monoclonal, and they share many of the molecular aberrations (like KRAS mutations) that are associated with adenocarcinomas.[4]
Molecular biology
Chromosomal rearrangements
Three membrane associated tyrosine kinase receptors are recurrently involved in rearrangements in adenocarcinomas: ALK, ROS1, and RET, and more than eighty other translocations have also been reported in adenocarcinomas of the lung.[5] Targeted therapies: ALK and ROS1 fusions proteins are both sensitive to treatment with the new ALK tyrosine kinase inhibitors (see the Atlas of Genetics and Cytogenetics in Oncology and Haematology,[6]).
Gene mutations
Common gene mutations in pulmonary adenocarcinoma affect many genes, including EGFR (20%), HER2 (2%), KRAS, ALK, BRAF, PIK3CA, MET (1%, associated with resistant disease), and ROS1. Most of these genes are kinases, and can be mutated in different ways, including amplification.[3]