Laryngeal cancer pathophysiology

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Omer Kamal, M.D.[2], Faizan Sheraz, M.D. [3]

Overview

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

Pathophysiology

Laryngeal cancer arises from squamous cells, which are cells that are normally involved in protection of upper respiratory airways.^[1]

Genetics

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:^[2]

Gross Pathology

On gross pathology, laryngeal cancer is characterized by:^[3]^[4]

Flattened plaques
Raised margins of the lesion
Mucosal ulceration

Microscopic Pathology

On microscopic histopathological analysis, laryngeal carcinoma is characterized by:^[5]^[6]^[7]^[8]

Spindle cells
Basaloid cells
Nuclear atypia
Abundant chromatin

Squamous cell carcinoma is subdivided histopathologically:^[5]^[6]^[9]

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:

Basaloid
Warty (condylomatous)
Verrucous
Papillary
Lymphoepithelial
Spindle cell

Immunohistochemistry

There are several immunohistochemistry markers of laryngeal carcinoma which include:^[10]^[11]

p63 positive
EBER negative
p16 negative
BCL2 positive/negative

References

↑ Koufman JA, Burke AJ (February 1997). “The etiology and pathogenesis of laryngeal carcinoma”. Otolaryngol. Clin. North Am. 30 (1): 1–19. PMID 8995133.
↑ de Miguel-Luken MJ, Chaves-Conde M, Carnero A (May 2016). “A genetic view of laryngeal cancer heterogeneity”. Cell Cycle. 15 (9): 1202–12. doi:10.1080/15384101.2016.1156275. PMC 4894505. PMID 26940775.
↑ Sessions DG (June 1976). “Surgical pathology of cancer of the larynx and hypopharynx”. Laryngoscope. 86 (6): 814–39. doi:10.1288/00005537-197606000-00009. PMID 933673.
↑ “journals.sagepub.com”.
↑ ^5.0 ^5.1 Hilly O, Raz R, Vaisbuch Y, Strenov Y, Segal K, Koren R, Shvero J (November 2012). “Thyroid gland involvement in advanced laryngeal cancer: association with clinical and pathologic characteristics”. Head Neck. 34 (11): 1586–90. doi:10.1002/hed.21972. PMID 22180291.
↑ ^6.0 ^6.1 Caldas-Magalhaes J, Kasperts N, Kooij N, van den Berg CA, Terhaard CH, Raaijmakers CP, Philippens ME (February 2012). “Validation of imaging with pathology in laryngeal cancer: accuracy of the registration methodology”. Int. J. Radiat. Oncol. Biol. Phys. 82 (2): e289–98. doi:10.1016/j.ijrobp.2011.05.004. PMID 21719209.
↑ MUSTAKALLIO S (August 1946). “Relation of microscopic structure of laryngeal cancer to radiocurability”. Acta radiol. 27 (5): 473–80. PMID 20286025.
↑ Franz B, Wetzel M (July 1980). “[Cytology of the early invasive laryngeal cancer (author’s transl)]”. Laryngol Rhinol Otol (Stuttg) (in German). 59 (7): 401–5. PMID 7453440.
↑ Lewis JS (March 2011). “Not your usual cancer case: variants of laryngeal squamous cell carcinoma”. Head Neck Pathol. 5 (1): 23–30. doi:10.1007/s12105-010-0232-0. PMC 3037456. PMID 21165725.
↑ Rodrigo JP, Martínez P, Allonca E, Alonso-Durán L, Suárez C, Astudillo A, García-Pedrero JM (March 2014). “Immunohistochemical markers of distant metastasis in laryngeal and hypopharyngeal squamous cell carcinomas”. Clin. Exp. Metastasis. 31 (3): 317–25. doi:10.1007/s10585-013-9630-5. PMID 24370715.
↑ Wittekindt C, Sittel C, Kvasnicka HM, Eckel HE (August 2006). “Immunohistochemistry of whole-organ sections of advanced human laryngeal cancer”. Eur Arch Otorhinolaryngol. 263 (8): 741–6. doi:10.1007/s00405-006-0055-5. PMID 16683119.

Template:WikiDoc Sources

[pmid8995133-1] Koufman JA, Burke AJ (February 1997). “The etiology and pathogenesis of laryngeal carcinoma”. Otolaryngol. Clin. North Am. 30 (1): 1–19. PMID 8995133.

[pmid26940775-2] Miguel-Luken MJ, Chaves-Conde M, Carnero A (May 2016). “A genetic view of laryngeal cancer heterogeneity”. Cell Cycle. 15 (9): 1202–12. doi:10.1080/15384101.2016.1156275. PMC 4894505. PMID 26940775.

[pmid933673-3] Sessions DG (June 1976). “Surgical pathology of cancer of the larynx and hypopharynx”. Laryngoscope. 86 (6): 814–39. doi:10.1288/00005537-197606000-00009. PMID 933673.

[urljournals.sagepub.com-4] “journals.sagepub.com”.

[pmid22180291-5] 5.0 ^5.1 Hilly O, Raz R, Vaisbuch Y, Strenov Y, Segal K, Koren R, Shvero J (November 2012). “Thyroid gland involvement in advanced laryngeal cancer: association with clinical and pathologic characteristics”. Head Neck. 34 (11): 1586–90. doi:10.1002/hed.21972. PMID 22180291.

[pmid21719209-6] 6.0 ^6.1 Caldas-Magalhaes J, Kasperts N, Kooij N, van den Berg CA, Terhaard CH, Raaijmakers CP, Philippens ME (February 2012). “Validation of imaging with pathology in laryngeal cancer: accuracy of the registration methodology”. Int. J. Radiat. Oncol. Biol. Phys. 82 (2): e289–98. doi:10.1016/j.ijrobp.2011.05.004. PMID 21719209.

[pmid20286025-7] MUSTAKALLIO S (August 1946). “Relation of microscopic structure of laryngeal cancer to radiocurability”. Acta radiol. 27 (5): 473–80. PMID 20286025.

[pmid7453440-8] Franz B, Wetzel M (July 1980). “[Cytology of the early invasive laryngeal cancer (author’s transl)]”. Laryngol Rhinol Otol (Stuttg) (in German). 59 (7): 401–5. PMID 7453440.

[pmid21165725-9] Lewis JS (March 2011). “Not your usual cancer case: variants of laryngeal squamous cell carcinoma”. Head Neck Pathol. 5 (1): 23–30. doi:10.1007/s12105-010-0232-0. PMC 3037456. PMID 21165725.

[pmid24370715-10] Rodrigo JP, Martínez P, Allonca E, Alonso-Durán L, Suárez C, Astudillo A, García-Pedrero JM (March 2014). “Immunohistochemical markers of distant metastasis in laryngeal and hypopharyngeal squamous cell carcinomas”. Clin. Exp. Metastasis. 31 (3): 317–25. doi:10.1007/s10585-013-9630-5. PMID 24370715.

[pmid16683119-11] Wittekindt C, Sittel C, Kvasnicka HM, Eckel HE (August 2006). “Immunohistochemistry of whole-organ sections of advanced human laryngeal cancer”. Eur Arch Otorhinolaryngol. 263 (8): 741–6. doi:10.1007/s00405-006-0055-5. PMID 16683119.

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