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==Overview==
==Overview==
Laryngeal cancers arise from squamous cell epithelium of the larynx. Most laryngeal cancers are [[squamous cell carcinoma]]s, reflecting their origin from the [[squamous cell]]s which form the majority of the laryngeal [[epithelium]]. [[Cancer]] can develop in any part of the [[larynx]], but the cure rate is affected by the location of the tumor. For the purposes of tumor [[Cancer staging|staging]], the larynx is divided into three anatomical regions: the [[glottis]] (true vocal cords, anterior and posterior commissures); the supraglottis ([[epiglottis]], [[arytenoids]] and [[aryepiglottic folds]], and [[Vocal folds#False vocal folds|false cords]]); the subglottis. Most laryngeal cancers originate in the [[glottis]]. Supraglottic cancers are less common, and subglottic tumors are least frequent. Laryngeal cancer may spread, either by direct extension to adjacent structures, by [[metastasis]] to regional cervical [[lymph node]]s or more distantly, through the blood stream. Distant metastates to the lung are most common. Laryngeal carcinoma may be classified into more than 14 subtypes based on anatomical and histological characteristics of the tumor. Laryngeal cancer arises from [[squamous cell]]s, which are cells that are normally involved in protection of airway. Genes involved in the pathogenesis of laryngeal cancer include ''[[P16 (gene)|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 cell]]s, basaloid cells, and nuclear atypia are characteristic findings of laryngeal cancer. Laryngeal carcinoma must be differentiated from laryngeal syphilis, [[lymphoma]], and [[chronic laryngitis]].<ref name=abc>Protocol applies to all invasive carcinomas of the larynx, including supraglottis, glottis, and subglottis.http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2011/Larynx_11protocol.pdf. Accessed on: October 28, 2015.</ref> The prevalence and incidence of laryngeal cancer is approximately 19.5 and 3.3 per 100,000 individuals in the United States, respectively.<ref name="SEER">Howlader N, Noone AM, Krapcho M, Garshell J, Miller D, Altekruse SF, Kosary CL, Yu M, Ruhl J, Tatalovich Z,Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA (eds). SEER Cancer Statistics Review, 1975-2011, National Cancer Institute. Bethesda, MD, http://seer.cancer.gov/csr/1975_2011/, based on November 2013 SEER data submission, posted to the SEER web site, April 2014.</ref> The estimated number of new cases in the United States in 2014 is 12,630 which corresponds to 0.8% of all new cancer cases.<ref name=cancer.gov>[http://seer.cancer.gov/statfacts/html/laryn.html SEER Stat Fact Sheets: Larynx Cancer]</ref> Laryngeal cancer is listed as a "rare disease" by the Office of Rare Diseases (ORD) of the National Institutes of Health (NIH), which means that laryngeal cancer affects less than 200,000 individuals in the US population.<ref name=NIH>{{cite web | title =Annual Report on the Rare Diseases and Conditions Research| url=http://rarediseases.info.nih.gov/ | publsiher=National Institutes of Health | accessdate=2007-03-22}}</ref> In the United Kingdom, 2,369 individuals were diagnosed with laryngeal cancer in 2011.<ref name=UK>[http://www.cancerresearchuk.org/cancer-info/cancerstats/types/larynx/ Cancer research UK]</ref> Common risk factors in the development of laryngeal cancer are smoking tobacco, chewing tobacco, and heavy alcohol consumption.<ref name=aaa>Hypopharyngeal cancer treatment. National Cancer Institute. http://www.cancer.org/cancer/laryngealandhypopharyngealcancer/detailedguide/laryngeal-and-hypopharyngeal-cancer-risk-factors. Accessed on October 26, 2015.</ref> According to the American Cancer Society, screening for laryngeal cancer is not recommended.<ref name=aaa>Can laryngeal and hypopharyngeal cancers be found early? Accessed on October 8, 2015. http://www.cancer.org/cancer/laryngealandhypopharyngealcancer/detailedguide/laryngeal-and-hypopharyngeal-cancer-detection</ref> The optimal therapy for laryngeal cancer depends on the stage at the time of diagnosis. The feasibility of surgery depends on the stage of laryngeal cancer at the time of diagnosis.<ref name=aaa>Management of primary tumor. Surgwiki. http://surgwiki.com/wiki/Otorhinolaryngology. Accessed October 28, 2015</ref>
[[Laryngeal cancer|Laryngeal carcinoma]] was first discovered by Dr. Morgagni, a Byzantine physician. Theodore Bilroth reported a century ago, the first few examples of primary [[malignant]] tumors. The surgery for [[laryngeal cancer]] started in the 19th century and kept advancing through the 20th century. [[Laryngeal cancer|Laryngeal carcinoma]] may be classified into more than 14 subtypes based on the [[anatomical]] and [[histological]] characteristics of the [[tumor]]. [[Anatomical]] [[classification]] includes [[Supraglottic laryngeal cancer|supraglottic]], [[glottic]] and [[Subglottic airway|subglottic]] [[laryngeal cancer]]. There are no established [[causes]] for [[laryngeal cancer]]. However, [[chromium]] or [[nickel]], [[asbestos]], [[alcohol]] and [[smoking]] have been associated with [[laryngeal cancer]]. The [[prevalence]] of [[laryngeal cancer]] is approximately 19.5 per 100,000 individuals in the United States. The [[incidence]] of laryngeal cancer is approximately 3.3 per 100,000 individuals in the United States. According to the American Cancer Society, [[screening]] for [[laryngeal cancer]] is not recommended. If left untreated, [[laryngeal cancer]] produces few [[symptoms]] early in the course. Once the [[tumor]] has expanded from its site of [[origin]], it may obstruct the airway. The hallmark of laryngeal cancer is [[hoarseness]]. A positive history of neck lump and [[hoarseness]] is suggestive of [[laryngeal cancer]]. Based on the location of the [[tumor]], [[symptoms]] may differ but commonly includes [[hoarseness]] or other voice changes, [[lump]] in the [[neck]], [[sore throat]], and [[Cough|persistent cough]]. The [[medical]] therapy combined with [[radiation]] has largely replaced the surgical cure for [[laryngeal cancer]]. However, the treatment truly depends on the stage at the time of [[diagnosis]]. Multiple factors will be taken into account when considering treatment like [[laryngeal]] preservation, maintaining the [[airway]], s[[Swallowing|wallowing]] and s[[Speech|peech]]. Induction includes three cycles of continuous infusion of [[cisplatin]] (100 mg/m2 on day 1) plus [[fluorouracil]] (1000 mg/m2/day )  followed by definitive [[radiation therapy]] in the induction phase and concurrent [[Cisplatin|cinsists of Cisplatin]] (100 mg/m2 on days 1, 22, and 43) with [[radiation therapy]]. The feasibility of surgery depends on the stage of laryngeal cancer at the time of diagnosis. The goal of treatment is to completely remove the [[tumor]], achieve [[tumor]] free margins and prevent the spread. The options of [[surgery]] can be transoral [[laser surgery]], transoral [[robotic surgery]], total [[laryngectomy]], and total [[laryngectomy]] with partial pharyngectomy
 
== Historical Perspective ==
[[Laryngeal cancer|Laryngeal carcinoma]] was first discovered by Dr. Morgagni, a Byzantine physician. Theodore Bilroth reported a century ago, the first few examples of primary [[malignant]] tumors. The surgery for [[laryngeal cancer]] started in the 19th century and kept advancing through the 20th century.  


==Classification==
==Classification==
Laryngeal carcinoma may be classified into more than 14 subtypes based on the anatomical and histological characteristics of the tumor.
[[Laryngeal cancer]] arises from [[squamous cell]]s, which are [[cells]] that are normally involved in protection of upper respiratory airway. [[Genes]] involved in the [[pathogenesis]] of [[laryngeal cancer]] include ''[[P16 (gene)|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 cell]]s, basaloid cells, and [[nuclear]] [[atypia]] are characteristic findings of [[laryngeal cancer]]


==Pathophysiology==
==Pathophysiology==
Line 13: Line 17:


==Causes==
==Causes==
There are no established direct causes for laryngeal cancer. Common risk factors for laryngeal cancer can be found [[Laryngeal cancer risk factors|'''here''']].<ref name=aaa>What are the risk factors for laryngeal and hypopharyngeal cancers?. Cancer.org. Accessed on October 13, 2015. http://www.cancer.org/cancer/laryngealandhypopharyngealcancer/overviewguide/laryngeal-and-hypopharyngeal-cancer-overview-what-causes</ref>
There are no established [[causes]] for [[laryngeal cancer]]. However, [[chromium]] or [[nickel]], [[asbestos]], [[alcohol]] and [[smoking]] have been associated with [[laryngeal cancer]]
==Differentiating Laryngeal cancer from other Diseases==
==Differentiating Laryngeal cancer from other Diseases==
Laryngeal carcinoma must be differentiated from laryngeal syphilis, [[lymphoma]], and [[chronic laryngitis]].<ref name=abc>Protocol applies to all invasive carcinomas of the larynx, including supraglottis, glottis, and subglottis.http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2011/Larynx_11protocol.pdf. Accessed on: October 28, 2015.</ref>
[[Laryngeal carcinoma]] must be differentiated from laryngeal syphilis, [[lymphoma]], and [[chronic laryngitis]]
==Epidemiology and Demographics==
==Epidemiology and Demographics==
The prevalence of laryngeal cancer is approximately 19.5 per 100,000 individuals in the United States.<ref name="SEER">Howlader N, Noone AM, Krapcho M, Garshell J, Miller D, Altekruse SF, Kosary CL, Yu M, Ruhl J, Tatalovich Z,Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA (eds). SEER Cancer Statistics Review, 1975-2011, National Cancer Institute. Bethesda, MD, http://seer.cancer.gov/csr/1975_2011/, based on November 2013 SEER data submission, posted to the SEER web site, April 2014.</ref> The incidence of laryngeal cancer is approximately 3.3 per 100,000 individuals in the United States.<ref name="SEER">Howlader N, Noone AM, Krapcho M, Garshell J, Miller D, Altekruse SF, Kosary CL, Yu M, Ruhl J, Tatalovich Z,Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA (eds). SEER Cancer Statistics Review, 1975-2011, National Cancer Institute. Bethesda, MD, http://seer.cancer.gov/csr/1975_2011/, based on November 2013 SEER data submission, posted to the SEER web site, April 2014.</ref> The estimated number of new cases in the United States in 2014 is 12,630 which corresponds to 0.8% of all new cancer cases.<ref name=cancer.gov>[http://seer.cancer.gov/statfacts/html/laryn.html SEER Stat Fact Sheets: Larynx Cancer]</ref> Laryngeal cancer is listed as a "rare disease" by the Office of Rare Diseases (ORD) of the National Institutes of Health (NIH), which means that laryngeal cancer affects less than 200,000 people in the US population.<ref name=NIH>{{cite web | title =Annual Report on the Rare Diseases and Conditions Research| url=http://rarediseases.info.nih.gov/ | publsiher=National Institutes of Health | accessdate=2007-03-22}}</ref> In the United Kingdom, 2,369 people were diagnosed with laryngeal cancer in 2011.<ref name=UK>[http://www.cancerresearchuk.org/cancer-info/cancerstats/types/larynx/ Cancer research UK]</ref>
The [[prevalence]] of [[laryngeal cancer]] is approximately 19.5 per 100,000 individuals in the United States. The [[incidence]] of laryngeal cancer is approximately 3.3 per 100,000 individuals in the United States.The estimated number of new cases in the United States in 2014 is 12,630 which corresponds to 0.8% of all new [[cancer]] cases. [[Laryngeal cancer]] is listed as a "[[rare disease]]" by the Office of Rare Diseases (ORD) of the National Institutes of Health (NIH), which means that [[laryngeal cancer]] affects less than 200,000 people in the US [[population]]. In the United Kingdom, 2,369 people were diagnosed with [[laryngeal cancer]] in 2011.


==Risk Factors==
==Risk Factors==
Common risk factors in the development of laryngeal cancer are smoking tobacco, chewing tobacco, and heavy alcohol consumption.<ref name=aaa>Hypopharyngeal cancer treatment. National Cancer Institute. http://www.cancer.org/cancer/laryngealandhypopharyngealcancer/detailedguide/laryngeal-and-hypopharyngeal-cancer-risk-factors Accessed on October 26, 2015.</ref>
Common risk factors in the development of [[laryngeal cancer]] are smoking [[tobacco]], chewing [[tobacco]], and heavy [[alcohol consumption]]
==Screening==
==Screening==
According to the American Cancer Society, screening for laryngeal cancer is not recommended.<ref name=aaa>Can laryngeal and hypopharyngeal cancers be found early? Accessed on October 8, 2015. http://www.cancer.org/cancer/laryngealandhypopharyngealcancer/detailedguide/laryngeal-and-hypopharyngeal-cancer-detection</ref>
According to the American Cancer Society, [[screening]] for [[laryngeal cancer]] is not recommended
==Natural History, Complications and Prognosis==
==Natural History, Complications and Prognosis==
If left untreated, laryngeal cancer produces few symptoms early in the course. Once the [[tumor]] has expanded from its site of origin, it may obstruct the airway. Common complications of laryngeal cancer include airway obstruction, neck disfigurement, and speaking difficulties. The prognosis varies with the type and stage of laryngeal cancer. Stage 4 squamous cell carcinoma of larynx has the most unfavorable prognosis.
If left untreated, [[laryngeal cancer]] produces few [[symptoms]] early in the course. Once the [[tumor]] has expanded from its site of [[origin]], it may obstruct the airway. Common complications of [[laryngeal cancer]] include [[airway obstruction]], [[neck]] disfigurement, and [[voice]] [[abnormalities]]. The [[prognosis]] varies with the type and stage of [[laryngeal cancer]]. Stage 4 [[squamous cell carcinoma]] of [[larynx]] has the most unfavorable prognosis. The 3-year survival rate for [[supraglottic laryngeal cancer]] and T3 transglottic [[carcinoma]] were 91.7% and 73.2%, respectively
 
Diagnosis
 
==Staging==
==Staging==
According to the [[TNM staging system]], there are 5 stages of laryngeal cancer based on the [[tumor]] size, [[lymph node]] involvement, and distant [[metastasis]].
According to the [[TNM staging system]], the stages of [[laryngeal cancer]] are based on the [[tumor]] size, [[lymph node]] involvement, and distant [[metastasis]]
==History and Symptoms==
===History and Symptoms===
The hallmark of laryngeal cancer is [[hoarseness]]. A positive history of neck lump and [[hoarseness]] is suggestive of laryngeal cancer. Common symptoms include lump in the neck, [[dysphagia]], and [[hoarseness]].
The hallmark of laryngeal cancer is [[hoarseness]]. A positive history of neck lump and [[hoarseness]] is suggestive of [[laryngeal cancer]]. Based on the location of the [[tumor]], [[symptoms]] may differ but commonly includes [[hoarseness]] or other voice changes, [[lump]] in the [[neck]], [[sore throat]], and [[Cough|persistent cough]]
==Physical Examination==
===Physical Examination===
Patients with laryngeal carcinoma are usually well appearing. Physical examination of patients with laryngeal carcinoma is usually remarkable for neck [[swelling]], [[hearing loss]], and [[stridor]].
Patients with [[laryngeal carcinoma]] are usually well appearing. [[Physical examination]] of patients with [[laryngeal carcinoma]] is usually remarkable [[neck]] [[swelling]], [[hearing loss]], and [[stridor]].
==CT==
 
Head and neck [[CT scan]] may be helpful in the diagnosis of laryngeal cancer. Findings on CT scan suggestive of laryngeal cancer include solid soft tissue nodule,  region of superficial thickening with increased enhancement, and obliteration of [[fat]] planes.
=== Laboratory findings ===
==MRI==
There are no [[diagnostic]] lab findings associated with [[laryngeal cancer]].
[[MRI]] may be helpful in the diagnosis of laryngeal cancer. Findings on MRI suggestive of laryngeal cancer include intermediate to low signal mass and soft tissue enhancement.<ref name=aaa>Laryngeal carcinoma MRI findings. Dr Smita Deb and A/Prof Pramit Phal. Radiopaedia 2015. http://radiopaedia.org/cases/trans-glottic-squamous-cell-carcinoma-1. Accessed on October 28, 2015.</ref>
 
==Other Imaging Findings==
=== Electrocardiogram ===
Other diagnostic studies for laryngeal cancer include laryngoscopy, which demonstrates tumor size and location. Small sessile or superficially spreading lesions can be difficult or impossible to diagnose. Fluoro-D-glucose positron emission tomography may be performed to detect metastases of laryngeal cancer.<ref name=abc>Protocol applies to all invasive carcinomas of the larynx, including supraglottis, glottis, and subglottis.http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2011/Larynx_11protocol.pdf. Accessed on: October 28, 2015.</ref>
There are no [[ECG]] findings associated with [[laryngeal cancer]].
==Other Diagnostic Studies==
 
Biopsy may be diagnostic of laryngeal cancer. Findings on biopsy diagnostic of laryngeal cancer include [[spindle cell]]s, basaloid cells, and nuclear atypia.
=== Chest X-ray ===
Chest [[x-rays]] may be performed to detect [[metastasis]] of laryngeal cancer to the [[lungs]].
 
=== Ultrasonography ===
[[Ultrasonography]] could be of value in the assessment of [[laryngeal carcinoma]] alongwith [[laryngoscopy]] with some calcifications of the [[thyroid cartilage]]. It helps to detect, localize and find out the [[invasion]] of [[laryngeal carcinoma]].
 
===CT scan===
Head and neck [[CT scan]] may be helpful in the [[diagnosis]] of [[laryngeal cancer]]. Findings on [[CT scan]] suggestive of [[laryngeal cancer]] include [[solid]] [[soft tissue]] [[nodule]],  region of [[superficial]] thickening with increased enhancement, and obliteration of [[fat]] planes.
===MRI===
[[MRI]] may be helpful in the [[diagnosis]] of [[laryngeal cancer]]. Findings on [[MRI]] suggestive of [[laryngeal cancer]] include intermediate to low signal mass and [[soft tissue]] enhancement. [[MRI]] is better than [[CT]] for evaluation of [[neural]] [[metastasis]], [[skull]] [[invasion]], and intracranial [[invasion]] of head and neck [[cancer]]
===Other Imaging Findings===
Other imaging findings for [[laryngeal cancer]] inlcude Fluoro-D-glucose [[positron emission tomography]] [[PET]] which is taken up more by actively [[metabolic]] cells. In case of small [[glottic]] [[tumors]] further [[imaging]]<nowiki/>may be unnecessary. [[Laryngoscopy]] can be helpful to visualize the [[tumor]].
===Other Diagnostic Studies===
Fine needle aspiration biopsy has high [[sensitivity]] and [[specificity]] for [[laryngeal cancer]]
==Medical Therapy==
==Medical Therapy==
The optimal therapy for laryngeal cancer depends on the stage at the time of diagnosis.
The [[medical]] therapy combined with [[radiation]] has largely replaced the surgical cure for [[laryngeal cancer]]. However, the treatment truly depends on the stage at the time of [[diagnosis]]. Multiple factors will be taken into account when considering treatment like [[laryngeal]] preservation, maintaining the [[airway]], s[[Swallowing|wallowing]] and s[[Speech|peech]]. Induction includes three cycles of continuous infusion of [[cisplatin]] (100 mg/m2 on day 1) plus [[fluorouracil]] (1000 mg/m2/day )  followed by definitive [[radiation therapy]] in the induction phase and concurrent [[Cisplatin|cinsists of Cisplatin]] (100 mg/m2 on days 1, 22, and 43) with [[radiation therapy]]
==Surgery==
==Surgery==
The feasibility of surgery depends on the stage of laryngeal cancer at the time of diagnosis.<ref name=aaa>Management of primary tumor. Surgwiki.http://surgwiki.com/wiki/Otorhinolaryngology. Accessed October 28, 2015</ref>
The feasibility of surgery depends on the stage of laryngeal cancer at the time of diagnosis. The goal of treatment is to completely remove the [[tumor]], achieve [[tumor]] free margins and prevent the spread. The options of [[surgery]] can be transoral [[laser surgery]], transoral [[robotic surgery]], total [[laryngectomy]], and total [[laryngectomy]] with partial pharyngectomy
==Primary Prevention==
==Primary Prevention==
Effective measures for the primary prevention of laryngeal cancer include [[smoking cessation]] and limiting or avoiding alcohol consumption.
Effective measures for the [[primary prevention]] of [[laryngeal cancer]] include [[smoking cessation]] and limiting or avoiding [[alcohol consumption]]
==Secondary Prevention==
==Secondary Prevention==
Secondary prevention measures of laryngeal cancer include routine physical examination and imaging at scheduled intervals after treatment. Dental screening and screening for thyroid cancers are recommended among patients who had received radiation therapy to the oral cavity and cervical region, respectively.<ref name="pmid23946171">{{cite journal| author=Pfister DG, Ang KK, Brizel DM, Burtness BA, Busse PM, Caudell JJ et al.| title=Head and neck cancers, version 2.2013. Featured updates to the NCCN guidelines. | journal=J Natl Compr Canc Netw | year= 2013 | volume= 11 | issue= 8 | pages= 917-23 | pmid=23946171 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23946171  }} </ref>
[[Secondary prevention]] measures of [[laryngeal cancer]] include routine [[physical examination]] and [[imaging]] at scheduled intervals after treatment. [[Dental]] [[screening]] and [[screening]] for [[thyroid cancers]] are recommended among [[patients]] who had received [[radiation therapy]] to the [[oral cavity]] and [[cervical]] region, respectively
 
<references />
==References==
{{reflist|2}}
 
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Latest revision as of 22:28, 29 July 2020

Laryngeal cancer Microchapters

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Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating Laryngeal cancer from other Diseases

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Diagnosis

Staging

History and Symptoms

Physical Examination

Laboratory Findings

Electrocardiogram

Chest X Ray

CT

MRI

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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 carcinoma was first discovered by Dr. Morgagni, a Byzantine physician. Theodore Bilroth reported a century ago, the first few examples of primary malignant tumors. The surgery for laryngeal cancer started in the 19th century and kept advancing through the 20th century. Laryngeal carcinoma may be classified into more than 14 subtypes based on the anatomical and histological characteristics of the tumor. Anatomical classification includes supraglottic, glottic and subglottic laryngeal cancer. There are no established causes for laryngeal cancer. However, chromium or nickel, asbestos, alcohol and smoking have been associated with laryngeal cancer. The prevalence of laryngeal cancer is approximately 19.5 per 100,000 individuals in the United States. The incidence of laryngeal cancer is approximately 3.3 per 100,000 individuals in the United States. According to the American Cancer Society, screening for laryngeal cancer is not recommended. If left untreated, laryngeal cancer produces few symptoms early in the course. Once the tumor has expanded from its site of origin, it may obstruct the airway. The hallmark of laryngeal cancer is hoarseness. A positive history of neck lump and hoarseness is suggestive of laryngeal cancer. Based on the location of the tumor, symptoms may differ but commonly includes hoarseness or other voice changes, lump in the neck, sore throat, and persistent cough. The medical therapy combined with radiation has largely replaced the surgical cure for laryngeal cancer. However, the treatment truly depends on the stage at the time of diagnosis. Multiple factors will be taken into account when considering treatment like laryngeal preservation, maintaining the airway, swallowing and speech. Induction includes three cycles of continuous infusion of cisplatin (100 mg/m2 on day 1) plus fluorouracil (1000 mg/m2/day ) followed by definitive radiation therapy in the induction phase and concurrent cinsists of Cisplatin (100 mg/m2 on days 1, 22, and 43) with radiation therapy. The feasibility of surgery depends on the stage of laryngeal cancer at the time of diagnosis. The goal of treatment is to completely remove the tumor, achieve tumor free margins and prevent the spread. The options of surgery can be transoral laser surgery, transoral robotic surgery, total laryngectomy, and total laryngectomy with partial pharyngectomy

Historical Perspective

Laryngeal carcinoma was first discovered by Dr. Morgagni, a Byzantine physician. Theodore Bilroth reported a century ago, the first few examples of primary malignant tumors. The surgery for laryngeal cancer started in the 19th century and kept advancing through the 20th century.

Classification

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. 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.

Causes

There are no established causes for laryngeal cancer. However, chromium or nickel, asbestos, alcohol and smoking have been associated with laryngeal cancer

Differentiating Laryngeal cancer from other Diseases

Laryngeal carcinoma must be differentiated from laryngeal syphilis, lymphoma, and chronic laryngitis

Epidemiology and Demographics

The prevalence of laryngeal cancer is approximately 19.5 per 100,000 individuals in the United States. The incidence of laryngeal cancer is approximately 3.3 per 100,000 individuals in the United States.The estimated number of new cases in the United States in 2014 is 12,630 which corresponds to 0.8% of all new cancer cases. Laryngeal cancer is listed as a "rare disease" by the Office of Rare Diseases (ORD) of the National Institutes of Health (NIH), which means that laryngeal cancer affects less than 200,000 people in the US population. In the United Kingdom, 2,369 people were diagnosed with laryngeal cancer in 2011.

Risk Factors

Common risk factors in the development of laryngeal cancer are smoking tobacco, chewing tobacco, and heavy alcohol consumption

Screening

According to the American Cancer Society, screening for laryngeal cancer is not recommended

Natural History, Complications and Prognosis

If left untreated, laryngeal cancer produces few symptoms early in the course. Once the tumor has expanded from its site of origin, it may obstruct the airway. Common complications of laryngeal cancer include airway obstruction, neck disfigurement, and voice abnormalities. The prognosis varies with the type and stage of laryngeal cancer. Stage 4 squamous cell carcinoma of larynx has the most unfavorable prognosis. The 3-year survival rate for supraglottic laryngeal cancer and T3 transglottic carcinoma were 91.7% and 73.2%, respectively

Diagnosis

Staging

According to the TNM staging system, the stages of laryngeal cancer are based on the tumor size, lymph node involvement, and distant metastasis

History and Symptoms

The hallmark of laryngeal cancer is hoarseness. A positive history of neck lump and hoarseness is suggestive of laryngeal cancer. Based on the location of the tumor, symptoms may differ but commonly includes hoarseness or other voice changes, lump in the neck, sore throat, and persistent cough

Physical Examination

Patients with laryngeal carcinoma are usually well appearing. Physical examination of patients with laryngeal carcinoma is usually remarkable neck swelling, hearing loss, and stridor.

Laboratory findings

There are no diagnostic lab findings associated with laryngeal cancer.

Electrocardiogram

There are no ECG findings associated with laryngeal cancer.

Chest X-ray

Chest x-rays may be performed to detect metastasis of laryngeal cancer to the lungs.

Ultrasonography

Ultrasonography could be of value in the assessment of laryngeal carcinoma alongwith laryngoscopy with some calcifications of the thyroid cartilage. It helps to detect, localize and find out the invasion of laryngeal carcinoma.

CT scan

Head and neck CT scan may be helpful in the diagnosis of laryngeal cancer. Findings on CT scan suggestive of laryngeal cancer include solid soft tissue nodule, region of superficial thickening with increased enhancement, and obliteration of fat planes.

MRI

MRI may be helpful in the diagnosis of laryngeal cancer. Findings on MRI suggestive of laryngeal cancer include intermediate to low signal mass and soft tissue enhancement. MRI is better than CT for evaluation of neural metastasis, skull invasion, and intracranial invasion of head and neck cancer

Other Imaging Findings

Other imaging findings for laryngeal cancer inlcude Fluoro-D-glucose positron emission tomography PET which is taken up more by actively metabolic cells. In case of small glottic tumors further imagingmay be unnecessary. Laryngoscopy can be helpful to visualize the tumor.

Other Diagnostic Studies

Fine needle aspiration biopsy has high sensitivity and specificity for laryngeal cancer

Medical Therapy

The medical therapy combined with radiation has largely replaced the surgical cure for laryngeal cancer. However, the treatment truly depends on the stage at the time of diagnosis. Multiple factors will be taken into account when considering treatment like laryngeal preservation, maintaining the airway, swallowing and speech. Induction includes three cycles of continuous infusion of cisplatin (100 mg/m2 on day 1) plus fluorouracil (1000 mg/m2/day ) followed by definitive radiation therapy in the induction phase and concurrent cinsists of Cisplatin (100 mg/m2 on days 1, 22, and 43) with radiation therapy

Surgery

The feasibility of surgery depends on the stage of laryngeal cancer at the time of diagnosis. The goal of treatment is to completely remove the tumor, achieve tumor free margins and prevent the spread. The options of surgery can be transoral laser surgery, transoral robotic surgery, total laryngectomy, and total laryngectomy with partial pharyngectomy

Primary Prevention

Effective measures for the primary prevention of laryngeal cancer include smoking cessation and limiting or avoiding alcohol consumption

Secondary Prevention

Secondary prevention measures of laryngeal cancer include routine physical examination and imaging at scheduled intervals after treatment. Dental screening and screening for thyroid cancers are recommended among patients who had received radiation therapy to the oral cavity and cervical region, respectively