Squamous cell carcinoma of the lung pathophysiology

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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

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.


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