Laryngeal cancer pathophysiology

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


Laryngeal cancer arises from squamous cells, which are cells that are normally involved in protection of upper respiratory airways. Genes involved in the pathogenesis of laryngeal cancer include p16, NOTCH1, cyclin D1, and TP53. On gross pathology, flattened plaques, mucosal ulceration, and raised margins of the lesion are characteristic findings of laryngeal cancer. On microscopic histopathological analysis, spindle cells, basaloid cells, and nuclear atypia are characteristic findings of laryngeal cancer.


Laryngeal cancer arises from squamous cells, which are cells that are normally involved in protection of upper respiratory airways.


Development of laryngeal cancer is the result of multiple genetic mutations. These mutations lead to activation of oncogenes and inactivation of tumor suppression genes which ultimately result in deregulated cellular proliferation. Genes involved in the pathogenesis of laryngeal cancer include:

Gross Pathology

On gross pathology, laryngeal cancer is characterized by:

  • Flattened plaques
  • Raised margins of the lesion
  • Mucosal ulceration

Microscopic Pathology

On microscopic histopathological analysis, laryngeal carcinoma is characterized by:[2]

Squamous cell carcinoma is subdivided histopathologically by the World Health Organization into:[2]

  • Keratinizing type:
    • Keratinization & intercellular bridges through-out most of the malignant lesion
  • Undifferentiated type:
    • Non-distinct borders/syncytial pattern
    • Nucleoli
  • Non keratinizing type:
    • Well-defined cell borders
    • Eosinophilia
    • Extra large nuclei/bizarre nuclei
    • Inflammation (lymphocytes, plasma cells)
    • Long rete ridges
    • Numerous beeds/blobs of epithelial cells that seem unlikely to be rete ridges

Squamous Cell Carcinoma Subtypes

There are several histological subtypes of squamous cell carcinoma of larynx which include:[2]

  • Basaloid
  • Warty (condylomatous)
  • Verrucous
  • Papillary
  • Lymphoepithelial
  • Spindle cell


There are several immunohistochemistry markers of laryngeal carcinoma which include:

  • p63 positive
  • EBER negative
  • p16 negative
  • BCL2 positive/negative[4]


  1. Media in category Laryngeal cancer. Wikimedia Commons 2015. Accessed on October 29, 2015
  2. 2.0 2.1 2.2 Protocol applies to all invasive carcinomas of the larynx, including supraglottis, glottis, and subglottis. Accessed on: October 28, 2015.
  3. 3.0 3.1 3.2 Head and neck SCC Librepathology. Accessed on October 26, 2015
  4. Nichols AC, Finkelstein DM, Faquin WC; et al. (2010). "Bcl2 and human papilloma virus 16 as predictors of outcome following concurrent chemoradiation for advanced oropharyngeal cancer". Clin. Cancer Res. 16 (7): 2138–46. PMID 20233885. doi:10.1158/1078-0432.CCR-09-3185.