In the name of God

Laryngeal CarcinomaLaryngeal Carcinoma

M. H. Baradaranfar M.D professor of otolaryngology

Head and Neck surgery Rhinologist

OverviewOverview

11,000 new cases of laryngeal 11,000 new cases of laryngeal cancer per year in the U.S.cancer per year in the U.S.

Accounts for 25% of head and neck Accounts for 25% of head and neck cancer and 1% of all cancerscancer and 1% of all cancers

One-third of these patients One-third of these patients eventually die of their diseaseeventually die of their disease

Most prevalent in the 6Most prevalent in the 6thth and 7 and 7thth decades of lifedecades of life

OverviewOverview

4:1 male predilection4:1 male predilection Downward shift from 15:1 post WWIIDownward shift from 15:1 post WWII Due to increasing public acceptance Due to increasing public acceptance

of female smokingof female smoking More prevalent among lower More prevalent among lower

socioeconomic class, in which it is socioeconomic class, in which it is diagnosed at more advanced stagesdiagnosed at more advanced stages

SubtypesSubtypes

Glottic Cancer: 59%Glottic Cancer: 59%

Supraglottic Cancer: 40%Supraglottic Cancer: 40%

Subglottic Cancer: 1%Subglottic Cancer: 1%

Most subglottic masses are extension Most subglottic masses are extension from glottic carcinomasfrom glottic carcinomas

HistoryHistory

The first laryngectomy for cancer of The first laryngectomy for cancer of the larynx was performed in 1883 by the larynx was performed in 1883 by BillrothBillroth

Patient was successfully fed by mouth Patient was successfully fed by mouth and fitted with an artificial larynxand fitted with an artificial larynx

In 1886 the Crown Prince Frederick of In 1886 the Crown Prince Frederick of Germany developed hoarseness as he Germany developed hoarseness as he was due to ascend the throne.was due to ascend the throne.

Crown Prince Frederick of GermanyCrown Prince Frederick of Germany

HistoryHistory

Was evaluated by Sir Makenzie of Was evaluated by Sir Makenzie of London, the inventor of the direct London, the inventor of the direct laryngoscopelaryngoscope

Frederick’s lesion was biopsied and Frederick’s lesion was biopsied and thought to be cancerthought to be cancer

He refused laryngectomy and later He refused laryngectomy and later died in 1888died in 1888

HistoryHistory Frederick was Frederick was

succeeded by Kaiser succeeded by Kaiser Wilhelm II, who along Wilhelm II, who along with Otto von with Otto von Bismark militarized Bismark militarized the German Empire the German Empire and led them into and led them into WW IWW I

Could an Could an Otolaryngologist have Otolaryngologist have prevented WW I?prevented WW I?

Risk FactorsRisk Factors

Risk FactorsRisk Factors

Prolonged use of tobacco and Prolonged use of tobacco and excessive EtOH use primary risk excessive EtOH use primary risk factorsfactors

The two substances together have a The two substances together have a synergistic effect on laryngeal synergistic effect on laryngeal tissuestissues

90% of patients with laryngeal 90% of patients with laryngeal cancer have a history of bothcancer have a history of both

Risk FactorsRisk Factors

Human Papilloma Virus 16 &18Human Papilloma Virus 16 &18 Chronic Gastric RefluxChronic Gastric Reflux Occupational exposuresOccupational exposures Prior history of head and neck Prior history of head and neck

irradiationirradiation

Histological TypesHistological Types

85-95% of laryngeal tumors are 85-95% of laryngeal tumors are squamous cell carcinomasquamous cell carcinoma

Histologic type linked to tobacco and Histologic type linked to tobacco and alcohol abusealcohol abuse

Characterized by epithelial nests Characterized by epithelial nests surrounded by inflammatory stromasurrounded by inflammatory stroma

Keratin Pearls are pathognomonicKeratin Pearls are pathognomonic

Histological TypesHistological Types

Verrucous CarcinomaVerrucous Carcinoma FibrosarcomaFibrosarcoma ChondrosarcomaChondrosarcoma Minor salivary carcinomaMinor salivary carcinoma AdenocarcinomaAdenocarcinoma Oat cell carcinomaOat cell carcinoma Giant cell and Spindle cell carcinomaGiant cell and Spindle cell carcinoma

AnatomyAnatomy

AnatomyAnatomy

AnatomyAnatomy

AnatomyAnatomy

AnatomyAnatomy

AnatomyAnatomy

AnatomyAnatomy

AnatomyAnatomy

Natural HistoryNatural History

Supraglottic tumors more Supraglottic tumors more aggressive:aggressive:– Direct extension into pre-epiglottic Direct extension into pre-epiglottic

spacespace– Lymph node metastasisLymph node metastasis– Direct extension into lateral Direct extension into lateral

hypopharnyx, glossoepiglottic fold, and hypopharnyx, glossoepiglottic fold, and tongue basetongue base

Natural HistoryNatural History

Glottic tumors grow slower and tend Glottic tumors grow slower and tend to metastasize late owing to a paucity to metastasize late owing to a paucity of lymphatic drainageof lymphatic drainage

They tend to metastasize after they They tend to metastasize after they have invaded adjacent structures with have invaded adjacent structures with better drainagebetter drainage

Extend superiorly into ventricular walls Extend superiorly into ventricular walls or inferiorly into subglottic spaceor inferiorly into subglottic space

Can cause vocal cord fixationCan cause vocal cord fixation

Natural HistoryNatural History

True subglottic tumors are uncommonTrue subglottic tumors are uncommon Glottic spread to the subglottic space is Glottic spread to the subglottic space is

a sign of poor prognosisa sign of poor prognosis Increases chance of bilateral disease Increases chance of bilateral disease

and mediastinal extensionand mediastinal extension Invasion of the subglottic space Invasion of the subglottic space

associated with high incidence of associated with high incidence of stomal reoccurrence following total stomal reoccurrence following total laryngectomy (TL)laryngectomy (TL)

PresentationPresentation

HoarsenessHoarseness– Most common symptomMost common symptom– Small irregularities in the vocal fold Small irregularities in the vocal fold

result in voice changesresult in voice changes– Changes of voice in patients with Changes of voice in patients with

chronic hoarseness from tobacco and chronic hoarseness from tobacco and alcohol can be difficult to appreciatealcohol can be difficult to appreciate

PresentationPresentation

Patients presenting with hoarseness Patients presenting with hoarseness should undergo an indirect mirror exam should undergo an indirect mirror exam and/or flexible laryngoscope evaluationand/or flexible laryngoscope evaluation

Malignant lesions can appear as friable, Malignant lesions can appear as friable, fungating, ulcerative masses or be as fungating, ulcerative masses or be as subtle as changes in mucosal colorsubtle as changes in mucosal color

Videostrobe laryngoscopy may be needed Videostrobe laryngoscopy may be needed to follow up these subtler lesionsto follow up these subtler lesions

PresentationPresentation

Good neck exam looking for cervical Good neck exam looking for cervical lymphadenopathy and broadening of lymphadenopathy and broadening of the laryngeal prominence is requiredthe laryngeal prominence is required

The base of the tongue should be The base of the tongue should be palpated for masses as wellpalpated for masses as well

Restricted laryngeal crepitus may be Restricted laryngeal crepitus may be a sign of post cricoid or a sign of post cricoid or retropharyngeal invasionretropharyngeal invasion

PresentationPresentation

Other symptoms include:Other symptoms include:– DysphagiaDysphagia– HemoptysisHemoptysis– Throat painThroat pain– Ear painEar pain– Airway compromiseAirway compromise– AspirationAspiration– Neck massNeck mass

Work upWork up

Biopsy is required for diagnosisBiopsy is required for diagnosis Performed in OR with patient under Performed in OR with patient under

anesthesiaanesthesia Other benign possibilities for Other benign possibilities for

laryngeal lesions include: Vocal cord laryngeal lesions include: Vocal cord nodules or polyps, papillomatosis, nodules or polyps, papillomatosis, granulomas, granular cell neoplasms, granulomas, granular cell neoplasms, sarcoidosis, Wegner’s granulomatosissarcoidosis, Wegner’s granulomatosis

Work upWork up

Other potential modalities:Other potential modalities:– Direct laryngoscopyDirect laryngoscopy– BronchoscopyBronchoscopy– EsophagoscopyEsophagoscopy– Chest X-rayChest X-ray– CT or MRICT or MRI– Liver function tests with or without USLiver function tests with or without US– PET ?PET ?

Staging- Primary Tumor (T)Staging- Primary Tumor (T)

TXTX Minimum requirements to assess Minimum requirements to assess primary tumor cannot be metprimary tumor cannot be met

T0T0 No evidence of primary tumorNo evidence of primary tumor

TisTis Carcinoma in situCarcinoma in situ

Staging- SupraglottisStaging- Supraglottis

T1T1 Tumor limited to one subsite of supraglottis with normal vocal Tumor limited to one subsite of supraglottis with normal vocal cord mobility cord mobility

T2T2 Tumor involves mucosa of more than one adjacent subsite of Tumor involves mucosa of more than one adjacent subsite of supraglottis or glottis, or region outside the supraglottis (e.g. supraglottis or glottis, or region outside the supraglottis (e.g. mucosa of base of the tongue, vallecula, medial wall of piriform mucosa of base of the tongue, vallecula, medial wall of piriform sinus) without fixation sinus) without fixation

T3T3 Tumor limited to larynx with vocal cord fixation and or invades Tumor limited to larynx with vocal cord fixation and or invades any of the following: postcricoid area, preepiglottic tissue, any of the following: postcricoid area, preepiglottic tissue, paraglottic space, and/or minor thyroid cartilage erosion (e.g. paraglottic space, and/or minor thyroid cartilage erosion (e.g. inner cortex) inner cortex)

T4aT4a Tumor invades through the thyroid cartilage and/or invades Tumor invades through the thyroid cartilage and/or invades tissue beyond the larynx (e.g. trachea, soft tissues of neck tissue beyond the larynx (e.g. trachea, soft tissues of neck including deep extrinsic muscles of the tongue, strap muscles, including deep extrinsic muscles of the tongue, strap muscles, thyroid, or esophagus) thyroid, or esophagus)

T4T4bb

Tumor invades prevertebral space, encases carotid artery, or Tumor invades prevertebral space, encases carotid artery, or invades mediastinal structures invades mediastinal structures

Staging- GlottisStaging- GlottisT1T1 Tumor limited to the vocal cord (s) (may involve anterior or Tumor limited to the vocal cord (s) (may involve anterior or

posterior commissure) with normal mobilty posterior commissure) with normal mobilty

T1aT1a Tumor limited to one vocal cord Tumor limited to one vocal cord

T1bT1b Tumor involves both vocal cords Tumor involves both vocal cords

T2T2 Tumor extends to supraglottis and/or subglottis, and/or with Tumor extends to supraglottis and/or subglottis, and/or with impaired vocal cord mobility impaired vocal cord mobility

T3T3 Tumor limited to the larynx with vocal cord fixation and/or Tumor limited to the larynx with vocal cord fixation and/or invades paraglottic space, and/or minor thyroid cartilage invades paraglottic space, and/or minor thyroid cartilage erosion (e.g. inner cortex) erosion (e.g. inner cortex)

T4aT4a Tumor invades through the thyroid cartilage, and/or invades Tumor invades through the thyroid cartilage, and/or invades tissues beyond the larynx (e.g. trachea, soft tissues of the tissues beyond the larynx (e.g. trachea, soft tissues of the neck including deep extrinsic muscles of the tongue, strap neck including deep extrinsic muscles of the tongue, strap muscles, thyroid, or esophagus muscles, thyroid, or esophagus

T4bT4b Tumor invades prevertebral space, encases carotid artery, or Tumor invades prevertebral space, encases carotid artery, or invades mediastinal structures invades mediastinal structures

Staging- SubglottisStaging- Subglottis

T1T1 Tumor limited to the subglottis Tumor limited to the subglottis

T2T2 Tumor extends to vocal cord (s) with normal or Tumor extends to vocal cord (s) with normal or impaired mobility impaired mobility

T3T3 Tumor limited the larynx with vocal cord fixation Tumor limited the larynx with vocal cord fixation

T4aT4a Tumor invades cricoid or thyroid cartilage and/or Tumor invades cricoid or thyroid cartilage and/or invades tissues beyond larynx (e.g. trachea, soft invades tissues beyond larynx (e.g. trachea, soft tissues of the neck including deep extrinsic muscles of tissues of the neck including deep extrinsic muscles of the tongue, strap muscles, thyroid, or esophagus) the tongue, strap muscles, thyroid, or esophagus)

T4bT4b Tumor invades prevertebral space, encases carotid Tumor invades prevertebral space, encases carotid artery, or invades mediastinal structures artery, or invades mediastinal structures

Staging- NodesStaging- Nodes

N0N0 No cervical lymph nodes positive No cervical lymph nodes positive

N1N1 Single ipsilateral lymph node ≤ 3cm Single ipsilateral lymph node ≤ 3cm

N2aN2a Single ipsilateral node > 3cm and Single ipsilateral node > 3cm and ≤6cm ≤6cm

N2bN2b Multiple ipsilateral lymph nodes, each Multiple ipsilateral lymph nodes, each ≤ 6cm≤ 6cm

N2cN2c Bilateral or contralateral lymph nodes, Bilateral or contralateral lymph nodes, each ≤6cm each ≤6cm

N3N3 Single or multiple lymph nodes > 6cm Single or multiple lymph nodes > 6cm

Staging- MetastasisStaging- Metastasis

M0M0 No distant metastasesNo distant metastases

M1M1 Distant metastases presentDistant metastases present

Stage GroupingsStage Groupings

00 TisTis N0N0 M0M0

II T1T1 N0N0 M0M0

IIII T2T2 N0N0 M0M0

IIIIII T3T3 N0N0 M0M0

T1-3T1-3 N1N1 M0M0

IVAIVA T4aT4a N0-2N0-2 M0M0

T1-4aT1-4a N2N2 M0M0

IVBIVB T4bT4b Any NAny N M0M0

Any TAny T N3N3 M0M0

IVCIVC Any TAny T Any NAny N M1M1

TreatmentTreatment

Premalignant lesions or Carcinoma in Premalignant lesions or Carcinoma in situ can be treated by surgical situ can be treated by surgical stripping of the entire lesionstripping of the entire lesion

CO2 laser can be used to accomplish CO2 laser can be used to accomplish this but makes accurate review of this but makes accurate review of margins difficultmargins difficult

TreatmentTreatment

Early stage (T1 and T2) can be treated Early stage (T1 and T2) can be treated with radiotherapy or surgery alone, with radiotherapy or surgery alone, both offer the 85-95% cure rate.both offer the 85-95% cure rate.

Surgery has a shorter treatment period, Surgery has a shorter treatment period, saves radiation for recurrence, but may saves radiation for recurrence, but may have worse voice outcomeshave worse voice outcomes

Radiotherapy is given for 6-7 weeks, Radiotherapy is given for 6-7 weeks, avoids surgical risks but has own avoids surgical risks but has own complicationscomplications

TreatmentTreatment

XRT complications include:XRT complications include:– MucositisMucositis– OdynophagiaOdynophagia– Laryngeal edemaLaryngeal edema– XerostomiaXerostomia– Stricture and fibrosisStricture and fibrosis– RadionecrosisRadionecrosis– HypothyroidismHypothyroidism

TreatmentTreatment

Advanced stage lesions often receive Advanced stage lesions often receive surgery with adjuvant radiationsurgery with adjuvant radiation

Most T3 and T4 lesions require a Most T3 and T4 lesions require a total laryngectomytotal laryngectomy

Some small T3 and lesser sized Some small T3 and lesser sized tumors can be treated with partial tumors can be treated with partial larygectomylarygectomy

TreatmentTreatment

Adjuvant radiation is started within 6 weeks Adjuvant radiation is started within 6 weeks of surgery and with once daily protocols of surgery and with once daily protocols lasts 6-7 weekslasts 6-7 weeks

Indications for post-op radiation include: T4 Indications for post-op radiation include: T4 primary, bone/cartilage invasion, extension primary, bone/cartilage invasion, extension into neck soft tissue, perineural invasion, into neck soft tissue, perineural invasion, vascular invasion, multiple positive nodes, vascular invasion, multiple positive nodes, nodal extracapsular extension, nodal extracapsular extension, margins<5mm, positive margins, CIS margins<5mm, positive margins, CIS margins, subglottic extension of primary margins, subglottic extension of primary tumor.tumor.

TreatmentTreatment

Chemotherapy can be used in Chemotherapy can be used in addition to irradiation in advanced addition to irradiation in advanced stage cancersstage cancers

Two agents used are Cisplatinum and Two agents used are Cisplatinum and 5-flourouracil5-flourouracil

Cisplatin thought to sensitize cancer Cisplatin thought to sensitize cancer cells to XRT enhancing its cells to XRT enhancing its effectiveness when used concurrently.effectiveness when used concurrently.

TreatmentTreatment

Induction chemotherapy with definitive Induction chemotherapy with definitive radiation therapy for advanced stage radiation therapy for advanced stage cancer is another optioncancer is another option

Studies have shown similar survival Studies have shown similar survival rates as compared to total rates as compared to total laryngectomy with adjuvant radiation laryngectomy with adjuvant radiation but with voice preservation.but with voice preservation.

Role in treatment still under Role in treatment still under investigationinvestigation

TreatmentTreatment

Modified or radical neck dissections are Modified or radical neck dissections are indicated in the presence of nodal diseaseindicated in the presence of nodal disease

Neck dissections may be performed in Neck dissections may be performed in patients with supra or subglottic T2 tumors patients with supra or subglottic T2 tumors even in the absence of nodal diseaseeven in the absence of nodal disease

N0 necks can have a selective dissection N0 necks can have a selective dissection sparing the SCM, IJ, and XIsparing the SCM, IJ, and XI

N1 necks usually have a modified N1 necks usually have a modified dissection of levels II-IVdissection of levels II-IV

Surgical OptionsSurgical Options

HemilaryngectomyHemilaryngectomy

No more than 1cm No more than 1cm subglottic extension subglottic extension anteriorly or 5mm anteriorly or 5mm posteriorlyposteriorly

Mobile affected cordMobile affected cord Minimal anterior Minimal anterior

contralateral cord contralateral cord involvementinvolvement

No cartilage invasionNo cartilage invasion No neck soft tissue No neck soft tissue

invasioninvasion

Supraglottic laryngectomySupraglottic laryngectomy T1,2, or 3 if only by T1,2, or 3 if only by

preepiglottic space preepiglottic space invasioninvasion

Mobile cordsMobile cords No anterior No anterior

commissure commissure involvementinvolvement

FEV1 >50%FEV1 >50% No tongue base No tongue base

disease past disease past circumvallate papillaecircumvallate papillae

Apex of pyriform sinus Apex of pyriform sinus not invlovednot invloved

Supracricoid LaryngectomySupracricoid Laryngectomy

Resection of true Resection of true vocal cords, vocal cords, supraglottis, supraglottis, thyroid cartilagethyroid cartilage

Leave arytenoids Leave arytenoids and cricoid ring and cricoid ring intactintact

Half of patients Half of patients remain dependent remain dependent on tracheostomyon tracheostomy

Total LarygectomyTotal Larygectomy

Indications:Indications:– T3 or T4 unfit for partialT3 or T4 unfit for partial– Extensive involvement of thyroid and Extensive involvement of thyroid and

cricoid cartilagescricoid cartilages– Invasion of neck soft tissuesInvasion of neck soft tissues– Tongue base involvement beyond Tongue base involvement beyond

circumvallate papillaecircumvallate papillae

Total LaryngectomyTotal Laryngectomy

Total LaryngectomyTotal Laryngectomy

Total LaryngectomyTotal Laryngectomy

Total LaryngectomyTotal Laryngectomy

Voice RehabilitationVoice Rehabilitation

Tracheostomal prosthesisTracheostomal prosthesis

ElectrolarynxElectrolarynx

Pure esophageal speechPure esophageal speech

ComplicationsComplications Inaccurate stagingInaccurate staging InfectionInfection Voice alterationsVoice alterations Swallowing difficultiesSwallowing difficulties Loss of taste and smellLoss of taste and smell FistulaFistula Tracheostomy dependenceTracheostomy dependence Injury to cranial nerves: VII, IX, X, XI, XIIInjury to cranial nerves: VII, IX, X, XI, XII Stroke or carotid “blowout”Stroke or carotid “blowout” HypothyroidismHypothyroidism Radiation induced fibrosisRadiation induced fibrosis

PrognosisPrognosis

After initial treatment patients are followed at After initial treatment patients are followed at 4-6 week intervals. After first year decreases to 4-6 week intervals. After first year decreases to every 2 months. Third and fourth year every every 2 months. Third and fourth year every three months, with annual visits after thatthree months, with annual visits after that

5 year survival5 year survival

Stage IStage I >95%>95%

Stage IIStage II 85-90%85-90%

Stage IIIStage III 70-80%70-80%

Stage IVStage IV 50-60%50-60%

PrognosisPrognosis

Patients considered cured after being Patients considered cured after being disease free for five yearsdisease free for five years

Most laryngeal cancers reoccur in the Most laryngeal cancers reoccur in the first two yearsfirst two years

Despite advances in detection and Despite advances in detection and treatment options the five year treatment options the five year survival has not improved much over survival has not improved much over the last thirty yearsthe last thirty years