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]

Overview

Hypopharyngeal cancer arises from squamous cells, which are cells that are normally involved in protection of aerodigestive tract. Genes involved in the pathogenesis of hypopharyngeal cancer include p16, NOTCH1, cyclin D1, and TP53. Hypopharyngeal cancer is associated with sideropenic dysphagia and Paterson Brown Kelly syndrome. On gross pathology, flattened plaques, mucosal ulceration, and raised margins of the lesion are characteristic findings of hypopharyngeal cancer. On microscopic histopathological analysis, spindle cells, basaloid cells, and nuclear atypia are characteristic findings of hypopharyngeal cancer.[1]

Pathophysiology

Hypopharyngeal cancer arises from squamous cells, which are cells that are normally involved in protection of aerodigestive tract. Development of hypopharyngeal cancer is the result of multiple genetic mutations. These mutations lead to activation of oncogenes and inactivation of tumor suppression genes which ultimately results in deregulated cellular proliferation.

Genetics

Genes involved in the pathogenesis of hypopharyngeal cancer include:

Associated Diseases

Hypopharyngeal carcinoma is associated with:[1]

Gross Pathology

On gross pathology, hypopharyngeal cancer is characterized by:[1]

  • Flattened plaques
  • Raised margins of the lesion
  • Mucosal ulceration
  • Tumor spread to piriform sinus

Microscopic Pathology

On microscopic histopathological analysis, hypopharyngeal carcinoma is characterized by:[1]

Overview

Pathophysiology

Gross Pathology

  • Gross pathology specimen of laryngeal cancer

    Gross pathology specimen of laryngeal cancer


Subclassification by site

It is generally divided the following way:[2]

 
 
 
 
 
 
 
 
Laryngeal cancer
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Supraglottis
 
 
Glottis
 
 
Subglottis

Features:[3][4]

  • Prevalence - glottis > supraglottis > subglottis.
  • Glottic carcinoma tends to present earlier (as it affects phonation) and, therefore, has a better prognosis.

SCC is subdivided by the WHO into:[5]

  • Keratinizing type (KT).
    • Worst prognosis.
  • Undifferentiated type (UT).
    • Intermediate prognosis.
    • EBV association.
  • Nonkeratinizing type (NT).
    • Good prognosis.
    • EBV association.

Microscopic

Features based on classification:[5]

  • KT subtype:
    • Keratinization & intercellular bridges through-out most of the malignant lesion.
  • UT:
    • Non-distinct borders/syncytial pattern.
    • Nucleoli.
  • NT:
    • Well-defined cell borders.

Invasion

Features:

  • 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.

Pitfalls:

  • Tangential cuts.
    • If you can trace the squamous cells from a gland to the surface it is less likely to be invasive cancer.

Notes on invasion:

Images

  • Laryngeal squamous carcinoma (Intermediate Magnification)[7]

    Laryngeal squamous carcinoma (Intermediate Magnification)[7]

  • Laryngeal squamous carcinoma (High Magnification)[7]

    Laryngeal squamous carcinoma (High Magnification)[7]

  • Laryngeal squamous carcinoma (Very High Magnification)[7]

    Laryngeal squamous carcinoma (Very High Magnification)[7]

Overview of subtypes

There are several subtypes:[8]

  • Basaloid - poor prognosis, usu. diagnosed by recognition of typical SCC.
  • Warty (Condylomatous).
  • Verrucous - good prognosis, rare.
  • Papillary.
  • Lymphoepithelial, rare.
  • Spindle cell, a common spindle cell lesion of the H&N.

Verrucous squamous cell carcinoma

Features:

  • Exophytic growth.
  • Well-differentiated.
  • "Glassy" appearance.
  • Pushing border.

DDx: papilloma.

Spindle cell squamous carcinoma

  • Key to diagnosis is finding a component of conventional squamous cell carcinoma.

IHC:

  • Typically keratin -ve.
  • p63 +ve.

DDx:

  • Spindle cell melanoma.
  • Mesenchymal neoplasm.

Basaloid squamous cell carcinoma

Features:

  • Need keratinization. (???)

DDx:

  • Neuroendocrine tumour.

Lymphoepithelial (squamous cell) carcinoma

See nasopharyngeal carcinoma.

IHC

References

  1. ↑ 1.0 1.1 1.2 1.3 Helliwell TR (2003). "acp Best Practice No 169. Evidence based pathology: squamous carcinoma of the hypopharynx". J Clin Pathol. 56 (2): 81–5. PMC 1769882. PMID 12560383.
  2. ↑ URL: http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2011/Larynx_11protocol.pdf. Accessed on: 2 May 2012.
  3. ↑ Template:Ref WMSP
  4. ↑ URL: http://www.health.am/cr/more/statistics-and-prognosis-for-cancer-of-the-larynx/. Accessed on: 2 May 2012.
  5. ↑ 5.0 5.1 Template:Ref Sternberg4
  6. ↑ Wenig BM (2002). "Squamous cell carcinoma of the upper aerodigestive tract: precursors and problematic variants" (PDF). Mod. Pathol. 15 (3): 229–54. doi:10.1038/modpathol.3880520. PMID 11904340. Unknown parameter |month= ignored (help)
  7. ↑ 7.0 7.1 7.2 Head and neck SCC Librepathology. http://librepathology.org/wiki/index.php/Squamous_cell_carcinoma_of_the_head_and_neck Accessed on October 26, 2015
  8. ↑ URL: http://www.pathconsultddx.com/pathCon/diagnosis?pii=S1559-8675%2806%2970297-2. Accessed on: March 9, 2010.
  9. ↑ URL: http://www.biomedcentral.com/1471-2407/6/146. Accessed on: March 9, 2010.
  10. ↑ 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. doi:10.1158/1078-0432.CCR-09-3185. PMID 20233885. Unknown parameter |month= ignored (help)


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