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Benign Vocal Fold LesionsSteven Smith, MD
Mentor: Michael Underbrink, MD
The University of Texas Medical Branch (UTMB Health)
Department of Otolaryngology – Head & Neck Surgery
Grand Rounds Presentation
November 26, 2013
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Outline Introduction
Prevalence
Anatomy
Common benign vocal cord lesions
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Introduction Normal voice requires laryngeal function to be
coordinated, efficient, and physiologically stable
Imbalances in this delicate system can affect voice
quality
Benign lesions of the vocal folds can cause imbalances
in this system
The exact prevalence of benign vocal cord lesions has
been hard to determine and there has been lack of
data
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Prevalence Cohen et al 2011
Large retrospective study looking at the US
claims database, MarketScan
January 2004 - December 2008 (55 million)
537,000 had an ICD-9 diagnosis of dysphonia
Point prevalence rate 1%
Females 1.2% and Males 0.74%
Benign vocal pathology (11%)
Limitations
PCP diagnosed acute laryngitis 67% of the time
Otolaryngologist – vocal cord pathology
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Anatomy Laryngeal skeleton consist of nine
cartilages
Main laryngeal structure formed by 3
unpaired cartilages
Thyroid, cricoid, and epiglottic
Remainder of the framework consist of
paired cartilages
Arytenoid, corniculate, and cuneiform
http://education-
portal.com/cimages/multimages/16/Larynx_
rear_view.png
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Anatomy Arytenoid
Articulates with the cricoid to
form the cricoarytenoid joint
Multiaxial joint (sliding, rocking,
twisting)
Vocal process (medially) and
muscular process (laterally)
Actions of the intrinsic muscles
change position and shape of
vocal cord
Simpson, Blake, and Clark Rosen. Operative Techniques in
Laryngology. Berlin: Springer Bln, 2008. Web.
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Anatomy Intrinsic muscles
Responsible for vocal fold motion
3 types
Abductor, adductors, and tensor
Abductor
Posterior cricoarytenoid
Sole abductor
Responsible for glottic airway
http://img.medscape.com/pi/emed/ckb/otolaryngology/
834279-863537-867575-1334667tn.jpg
http://bedahunmuh.files.wordpress.com/2010/05/action-
of-intrinsic-muscles-of-larynx.jpg
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Anatomy Adductors
Thyroarytenoid
Two muscular bellies
Lateral – shortens and adducts
Medial – shortens and thickens
Lateral cricoarytenoid
Lengthening and adduction
Interarytenoids (oblique and transverse)
Only unpaired intrinsic muscles
Closure of posterior glottis
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Anatomy Tensor
Cricothyroid
Two muscle bellies
Vertical oriented
Oblique oriented
Tightening and lengthening
http://muscular-system.blogspot.com/2012/05/cricothyroid-
muscle.html
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Anatomy Blood supply
Superior laryngeal artery
Inferior laryngeal artery
http://www.rahulgladwin.com/medimages/plog-
content/images/free-usmle-medical-images/larynx-
anatomy/larynx-arterial-supply.jpg
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Anatomy
Nerve supply
Superior laryngeal nerve (inferior
vagal ganglion)
Two branches
Internal branch - sensory
External branch – motor (cricothyroid)
Recurrent laryngeal nerve
Branch of the vagus nerve
Left side
Right side
Provides sensory innervation to the
infraglottis and motor innervation to all
intrinsic muscles except cricothyroid
https://web.duke.edu/anatomy/Lab21/Lab2
1_clip_image002_0019.jpg
http://www.drmkotb.com/myimages/Recurrent
%20Laryngeal%20nerves.jpg
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Anatomy Histology
Superficial layer – stratified squamous
epithelium
Lamina propria
Superficial (Reinke’s space)
Loose fibrous matrix (few fibroblast)
Intermediate
Elastin
Deep
Fibroblast and collagen (dense)
Muscle – vocalis muscle (medial
portion of the thyroarytenoid musle)
http://ej.iop.org/images/1748-
605X/7/2/024103/Full/bmm406629f1_online.jpg
Simpson, Blake, and Clark Rosen. Operative Techniques in
Laryngology. Berlin: Springer Bln, 2008. Web.
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Anatomy Mucosa and vocal ligament extend
over the vocal process
Cartilaginous (aphonatory)
Posterior one-third
Membranous (phonatory)
Anterior two-thirds
Important anatomical feature
Most benign lesions affect the membranous portion
http://www.ncvs.org/ncvs/tutorials/voiceprod/images/Fig.7-6bcopy.jpg
http://classconnection.s3.amazonaws.com/704/flashcards/586704/png/cartilage1310578901682.
png
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Larynx Major functions
Airway protection
Most important
Respiration
Gateway to airflow
Phonation
Most complex and highly
specializedhttp://www.nature.com/gimo/contents/pt1/images/gimo39-f2.jpg
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Mucosal Wave Body-cover theory
Wavelike motion of mucosa (normal speech)
Cover – mucosa
Body – ligament and muscle
Videostroboscopy Gold-standard
Magnified
Mucosal vibratory patterns
Cummings
http://origin-ars.els-cdn.com/content/image/1-s2.0-
S0030666505702383-f069902.jpg
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Normal Videostroboscopy
Simpson, Blake, and Clark Rosen. Operative Techniques in
Laryngology. Berlin: Springer Bln, 2008. Web.
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Benign Vocal Cord Lesions Can be divided into two categories
Non-neoplastic
Vocal nodules
Vocal Polyp
Vocal Cyst
Reinke’s edema
Granuloma
Leukoplakia
Intracordal scars
Neoplastic
Papilloma
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Benign Non-neoplastic Vocal
Cord Lesions Majority of vocal fold lesions
Vibratory injury
Multifactorial
Extroverts, talkativeness
Occupation
Smoking, acid reflux, allergy, and
infection
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Vocal Cord Nodules Children and adult females
Presentation
Hoarseness of variable duration, can have varying degrees of breathiness and vocal breaks
Voice misuse or abuse (professional singers, teachers, other occupations with high voice demands)
www.britishvoiceassociation.org.uk/voice_information/nodulesDM.jpg
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Vocal Cord Nodules Bilateral
Junction of the anterior to middle
membranous portion of vocal fold
Vary in size, symmetry, contour, and
color
Pathological sequence
Forceful or prolonged vibration at the
membranous (vibratory) vocal cord
Edema and congestion
Long-term vocal abuse leads to
hyalinization of the SLP
http://mmd.sagepub.com/content/2/2/95/F3.large.jpg
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Vocal Cord Nodules Videostroboscopy
Hourglass appearance
Relatively symmetrical mucosal wave
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Vocal Cord Nodules Management
Voice therapy
Primary treatment
Optimize laryngeal environment
Phonotraumatic behaviors, guidelines for voice use,
optimizing hydration
Medical
Reflux, smoking
Surgical
Botox, Steroids
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Vocal Polyps Unilateral lesions
Broad based or pedunculated
Red, white, or translucent lesions at
anterior/middle third along the free
edge
Vocal abuse, anticoagulant use
Two types
Hemorrhagic – abrupt onset – extreme
vocal effort
Nonhemorrhagic (pseudocyst) –
outpouchings of inflamed SLP
http://voicedoctor.net/sites/default/files/2013-02-11_vid4_rig-002019
stop.jpg
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Vocal Polyps Pathophysiology
Shearing forces
Capillary rupture and focal
accumulation of blood or
hematoma
Inflammatory cells infiltrate
New matrix
http://mmd.sagepub.com/content/2/2/95/F3.large.jpg
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Vocal Polyps Videostroboscopy
Usually have intact mucosal waves
Phase asymmetry with impaired glottic closure
http://www.youtube.com/watch?feature=player_
detailpage&v=gXeR__rbrl4
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Vocal Polyps Management different based on polyp size
Conservative management for small polyps
Management
Medical
Discontinue anticoagulants, reflux
Voice therapy
Small polyps
Surgical
Office based pulse dye laser (585nm)
Small hemorrhagic polyps
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Vocal Cord Cyst Unilateral but can be bilateral
Sac like structure within the lamina
propria, yellow or white in color,
distinct and defined border
Two subtypes
Epidermoid
Stratified squamous epithelium
Vocal abuse or congenital
Mucous retention
Cylindrical epithelium
Spontaneously
http://www.ghorayeb.com/files/Laryngeal_Cyst__1_.JPG
http://mmd.sagepub.com/content/2/2/95/F3.large.jpg
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Vocal Cord Cyst Pathogenesis
Epidermoid vocal cord cyst
Epithelial cells buried
congenitally
Healing mucosa – vocal
abuse
Mucous retention cyst
Plugging of mucous gland
Upper respiratory infection,
voice overuse, and acid
reflux
http://fauquierent.blogspot.com/2011/10/new-webpage-on-vocal-
cord-cysts-and.html
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Vocal Cord Cyst Videostrobe
Asymmetrical mucosal wave
Decreased on side of lesion
Glottic closure depends on the size of the cyst
https://www.youtube.com/watch?feature=player_detailpage&v=byEc85zMHpY
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Vocal Cord Cyst Management
Surgical – mainstay of treatment
Supportive measures (hydration, reflux)
Voice therapy
Limited role
Epidermoid type
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Reactive Lesions Response to unilateral vocal cord lesion
Reactive callus with vocal cord hyperplasia
Can be confused with vocal nodules
http://www.voiceproblem.org/images/vf_reactive_500.jpg
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Reactive Lesions Videostroboscopy
Hourglass appearance
Wave asymmetry unlike vocal nodules
https://www.youtube.com/watch?feature=player_detailpage&v=IWV9D-2F6Ac
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Reactive Lesions Management
Treat primary lesion
Conservative management
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Reinke’s Edema Polypoid corditis, reinke’s edema, or
smoker’s polyps
Bilateral diffuse polyposis
Chronic irritant exposure
Middle aged, talkative women with a
long-term history of smoking
Lower pitch (masculine range)
Outpouchings of the membranous
vocal cord
Water balloon appearance
http://www.susansienko.com/media/photo/mucosal/reinke.html
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Reinke’s Edema Videostroboscopy
Decreased mucosal wave
Phase asymmetry due to ball-valving and asymmetric
edema
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Reinke’s Edema Management
Medical - smoking cessation
Voice therapy
may help introduce optimal vocal behavior
reduce size of the polyp and improve vocal functioning
Surgery necessary when the voice remains unacceptable
to patient
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Vocal Granuloma Primarily in men
Posterior one-third or cartilaginous glottis
Speech may be normal
Vocal cord trauma Associated with acid reflux, chronic
cough, throat clearing, and intubation
Pathophysiology Forceful closure of the arytenoids or
direct abrasion of the mucosa over the arytenoid perichondrium from pressure necrosis or coughing on an ET tube
http://voiceproblem.org/disorders/granuloma/granulom
a_slide1.html
Altman, Kenneth W. "Vocal Fold Masses." Otolaryngologic
Clinics of North America 40.5 (2007): 1091-108.
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Vocal Granuloma Videostroboscopy
Mucosal wave present
Location in cartilaginous posterior vocal cord
Large lesions can effect closure
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Vocal Granuloma Management
Treat underlying cause of irritation
Medical
Anti-reflux regimen
Spontaneously resolve over 3-6 months
Voice therapy
Surgical
Recurrence is common
Reserved for lesions
Enlarging
Affecting the voice
Suspicion for malignancy
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Capillary Ectasia Female singers
Hoarseness after short periods of singing
Abnormal dilation of capillaries, can also present as clusters
Pathophysiology
Vibratory microtrauma lead to capillary angiogenesis
Predisposes
Increased vulnerability to mucosal swelling
Vocal fold hemorrhage
Hemorrhagic polyp formationhttp://emedicine.medscape.com/article/866318-overview
http://www.casa.org/sites/default/files/photos/image_65/Fig%204%20Vocal%
20fold%20hemorrhage.jpg
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Capillary Ectasia Management
Medical
Discontinue anticoagulants
Acid reflux
Voice therapy – behavioral changes for voice abusers
Surgical
Patients who fail conservative management
Spot coagulation is an excellent option
CO2 laser - scarring
KTP (532nm) laser
Angiolytic
Selectively ablate vessels
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Intracordal Scarring Aphonia to relatively normal speaking
voice
Scarred, stiff vocal fold cover
Inflammation, vocal trauma, vocal cord
hemorrhage
Scarring of the SLP or Reinke’s space
Surgery involving lamina propria and
repeated epithelial procedure
Pathophysiology
Scaring adheres the mucosa to the
underlying vocal ligament, disrupting the
ability of the mucosa to oscillate freely
http://www.entandallergy.com/vas/gallerydetails/Sca
rring
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Intracordal Scarring Videostroboscopy
Markedly reduced or absent mucosal wave usually
asymmetric
Often effects phase closure
http://www.youtube.com/watch?feature=player_embedded&v=le9PegXRRvA
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Intracordal Scarring Management
Medical
General medical issues that affect voice should be optimized
Voice therapy
Voice building approach
Strengthen the muscles involved in phonation
“Phonatory massage”
Surgical
Incision with elevation of mucosa above scar with early voice
therapy
Prevention
Precise surgical technique
Earl treatment of vocal trauma
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Leukoplakia White hyperkeratotic plaque represents
change in epithelium
10.2 per 100,000 (Males)
2.1 per 100,000 (Females)
Pathophysiology unknown
Chronic irritation – smoking
3 stages
No dysplasia -> mild to moderate dysplasia -> severe dysplasia
8-14% chance of malignant transformation
http://dc357.4shared.com/img/njlWXqcC/s3/13bfe22
50c0/leukoplakia_left_vocal_cord.jpg
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Leukoplakia Videostroboscopy
Normal to sluggish mucosal wave
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Leukoplakia Videostroboscopy
Can vary in severity but a mucosal wave should be
present
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Leukoplakia Tissue diagnosis is necessary to rule out malignancy
Surgical
Excision or laser
Stage
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Benign Vocal Cord
Neoplasms
http://img.medscape.com/article/726/576/726576-fig2.jpg
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Vocal Cord Papilloma Most common benign neoplasm (84%)
Prevalence Rate
4.3 per 100,000 children
1.8 per 100,000 adults
HPV (strains 6 and 11 most common)
Type 11 associated with more aggressive disease
HPV types 16 and 18 higher risk of malignant transformation
200 fold increased risk of acquiring RRP if the mother is infected with genital HPV at birth
http://voicehealth101.com/content-images/Papilloma1.png
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Papilloma Two types
Juvenile
More aggressive and bulky,
exuberant tissues resembling
“clusters of grapes”
Adult-onset
More localized, usually less
aggressive, less exophytic with a
velvety appearance and little
projection from the surface of the
vocal cord
http://www.bbivar.com/vidimg/papilloma.jpg
http://www.portaldemedicina.com/pdf/orl_papiloma_laringe
o.pdf
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Papilloma Videostroboscopy
Mass effect with decreased mucosal wave
https://www.youtube.com/watch?feature=player_detailpage&v=t4YbV6enzOs
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Papilloma Management
Surgery
CO2 laser
Most widely accepted
Risk – scarring
Pulse Dye and KTP
Microdebrider
Bulky lesions
Adjuvant treatment
Interferon, Indole-3-carbinol
Cidofovir (antiviral)
Bevacizumab (trials)
Vaccine (Gardasil)
Incidence of RRP
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Cidofovir Prodrug (1995) not approved for
intralesional vocal cord injection
Used as an adjunct to RRP refractory to
surgery
Only approved for IV treatment of CMV
retinitis in acquired immunodeficiency
patients
Side effects
Nephrotoxicity, hepatic dysfunction, and
ocular toxicity
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Cidofovir Concern raised about cidofovir increasing malignant
potential
Studies have shown that 2-3% of patient with RRP have
malignant transformation
Equivalent to patients with and without cidofovir exposure
Gilead general warning letter (2011)
Warning against off-label use of cidofovir
Nephrotoxicity, neutropenia, oncogenicity, and fatalities
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Cidofovir 2012
International multicenter retrospective study
Evaluate the safety of cidofovir for intralesional laryngeal
injections
635 RRP and 275 treated with cidofovir
No statistical difference in occurrence of neutropenia or renal
dysfunction before or after cidofovir treatment
No statistical difference in upper airway and tracheal
malignancies between the cidofovir group and non cidofovir
group
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Bevacizumab Monoclonal antibody inhibits VEGF
(antiangiogenic activity)
Hypothesized - synergistic affect with KTP laser (photoangiolysis)
Zeitals et al 2011
Prospective study of 20 adult patients with bilateral disease
Treated with 532nm pulsed KTP laser 4 times at 6 week intervals
Bevacizumab injected in the vocal cord with the greater volume of disease at presentation
Contralateral vocal cord was injected with saline
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Bevacizumab Findings
No local or systemic complications
3 subjects, no noticeable disease in either cord
16 subjects had less disease in the Bevacizumab treated
cord
1 had more disease in the Bevacizumab treated cord
Conclusion
Injection with antiangiogenic medications shows potential
to improve KTP laser treatment and may decrease the
frequency of treatments
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Conclusion Benign vocal cord lesions are common pathologies that
will be seen in clinic
Recognizing and correctly diagnosing the lesions are important in treatment outcomes
Videostroboscopy
Understanding the goals of the patient are important in deciding the best treatment options
Preservation of the normal anatomy is important to optimize vocal outcomes
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References Altman, Kenneth W. "Vocal Fold Masses." Otolaryngologic Clinics of North America 40.5 (2007): 1091-108.
Cohen, Seth M., et al. "Prevalence and causes of dysphonia in a large treatment‐seeking population." The Laryngoscope 122.2 (2012): 343-348.
Cummings, Charles W., and Paul W. Flint. "Benign Vocal Fold Mucosal Disorders." Cummings Otolaryngology - Head and Neck Surgery. Philadelphia, PA: Mosby Elsevier, 2010.
Gi, REA Tjon Pian, et al. "Safety of intralesional cidofovir in patients with recurrent respiratory papillomatosis: an international retrospective study on 635 RRP patients." European Archives of Oto-Rhino-Laryngology (2013): 1-9.
Karkos, Petros D., and Maxwell McCormick. "The etiology of vocal fold nodules in adults." Current Opinion in Otolaryngology & Head and Neck Surgery 17.6 (2009): 420-423.
Martins, Regina Helena Garcia, et al. "Vocal Polyps: Clinical, Morphological, and Immunohistochemical Aspects." Journal of Voice25.1 (2011): 98-106.
Simpson, Blake, and Clark Rosen. Operative Techniques in Laryngology. Berlin: Springer Bln, 2008.
Venkatesan, Naren N., Harold S. Pine, and Michael P. Underbrink. "Recurrent respiratory papillomatosis." Otolaryngologic Clinics of North America 45.3 (2012): 671.
Zeitels, Steven M., et al. "Local injection of bevacizumab (Avastin) and angiolytic KTP laser treatment of recurrent respiratory papillomatosis of the vocal folds: a prospective study." The Annals of otology, rhinology, and laryngology 120.10 (2011): 627-634.