Laryngeal Tumor

Anatomi laring

Benign laryngeal lesions

PAPILLOMATOSIS onset : 24 years. Rare > 40. Multiple Warty lesions true and false vocal cords.

Laryngeal papillomatosis

Recurrent respiratory papillomatosis (RRP)

exophytic warty lesions, primarily within the larynx, may be found in the nose, pharynx, and trachea. benign significant morbidity and mortality. juvenile-onset RRPages of 2 and 4 years, more aggressive than adult-onset disease (peaks in the third decade)

Pathogenesis
caused by human papilloma virus (HPV)
subtypes 6 and 11 >> subtypes 16 and 18 <<

HPV 6 and 11 genital papillomatosis, transmission : from the genital tract Vertical transmission of the virus from mother to child :
ascending uterine infection or direct contact in the birth canal.

Clinical Findings
warty growths in the larynx: multiple, friable, irregular affect the true and false vocal cords are also found in other parts of the larynx and upper aerodigestive tract. Presentation depends on the site of the lesion.
glottic lesions dysphonia supraglottic lesions stridor.

Treatment
HPV cannot be eradicated from the larynx. HPV DNA can be detected in otherwise normal mucosa. The aim of treatment : to remove symptomatic lesions with minimal morbidity. Techniques :
CO2 laser resection cold steel dissection or use of the laryngeal microdebrider.

 Tracheostomy should be avoided distal airway involvement. Adjuvant treatments : intralaryngeal injection of cidofovir (Vistide) no conclusive evidence of efficacy. A vaccine for HPV 6, 11, 16, and 18
Trials significantly reduce the incidence of RRP.

Prognosis
Spontaneous remission Recurrence can arise many years later. There is a small risk of malignant change.

VOCAL CORD NODULES

Usually affects children or individuals who use their voices professionally. History of voice abuse common, such as frequent shouting in a young child. Bilateral, pale lesions at the junction of the anterior one third and posterior two thirds of the vocal cords.

Vocal nodule

General Considerations
Most common cause of persistent dysphonia in children. Deterioration in the voice quality singers nodules. Treatment conservative : speech therapy how to use the voice appropriately often promotes regression of the vocal cord nodules.

Clinical Findings
Laryngoscopy : Small, welldefined vocal cord lesions. Distinguishable from the normal vocal fold : whitish hue, at the junction of the anterior one third and posterior two thirds of the vocal fold. Bilateral, though often asymmetric.

Treatment
SPEECH THERAPY First-line treatment. Mainstay of treatment in both children and adults. Photodocumentation of the nodules in voice clinic indicates the treatment progress and aids patient compliance during speech therapy.

MICROLARYNGOSCOPY performed under the following circumstances: noncompliance of the patient prevents examination; in adults, either when microsurgical excision of the nodules is considered or when the diagnosis is not clear. Nodules may be excised using appropriate microsurgical instruments, or vaporized using a pulsed CO2 laser.

VOCAL CORD POLYPS

Usually unilateral, pedunculated lesions. Associated with smoking and voice abuse. Located throughout the glottis, particularly between the anterior and middle thirds of the vocal folds.

Vocal cord polyp

 Most commonly found in men with a history of voice abuse and heavy smoking. Treatment : most often surgical to confirm the diagnosis, exclude any coexisting malignant neoplasms, and provide resolution. Conservative voice therapy is often not successful.

Clinical Findings
Pedunculated, unilateral Morphologically similar to the laryngeal epithelium. Often occur on the true vocal folds May have noticeable vascular markings. Generally occur at the point of maximal vibration, the middle of the true junction of the anterior and middle thirds of the vocal fold

Treatment
microlaryngoscopic examination of the larynx + excision to confirm the diagnosis and exclude any other coexistent pathology. Large polyp may conceal an occult, early laryngeal squamous cell carcinoma. Excision is performed using appropriate microsurgical instruments, or laser. Smoking and vocal abuse should also be addressed.

LARYNGEAL CYSTS
Mucous glands are found throughout the larynx, with the exception of the medial edge of the vocal cord, and associated cysts may therefore occur also throughout the larynx. Their presentation and treatment are dictated primarily by their site; therefore, they are dealt with here on this basis.

1. Intracordal Cysts
Often found within the middle third of the vocal cords. Unilateral, associated small area of hyperkeratosis on opposite cord. Do not respond to speech therapy. Intracordal cysts may be simple mucous retention cysts or epidermoid cysts containing keratin. .

Clinical Findings Laryngoscopy : unilateral cyst, usually of the middle third of the vocal cord with a corresponding area of hyperkeratosis on the opposite cord. Treatment Do not respond to voice therapy Should be excised with phonosurgical instruments, using a local flap technique.

2. Saccular Cysts
May be congenital or acquired. Adults generally present with voice change. Children commonly present with airway compromise. Unilateral supraglottic mass, overlying mucosa unremarkable.

 Arises as a diverticulum from the anterior end of the laryngeal ventricle. It extends upward between the false vocal fold and the inner surface of the thyroid cartilage. Contains mucus-secreting glands. As a result of obstruction of these glands, which may be secondary to a congenital anomaly or acquired.

Clinical Findings
Examination reveals expansion of the aryepiglottic fold by the cyst within it. May extend into the neck through the thyrohyoid membrane. Computed tomography (CT) a cyst expanding the supraglottis; the absence of air within the lesion distinguishes it from a laryngocele. Mesodermal tissue may be apparent in the wall of congenital saccular cysts and may influence the surgical approach.

Treatment
Managed endoscopically marsupialization or excision (CO2 laser). Lesions extending beyond the larynx and congenital cysts containing mesodermal elements transcervical approach. The excised cyst should undergo histologic examination. Oncocytic metaplasia (oncocytic cysts) more often multiple and more prone to recurrence.

LARYNGOCELE
Generally present as an anterior triangle neck mass. Increase in size with elevated intralaryngeal pressure. Associated with malignancy in the laryngeal ventricle.

 A laryngocele is an abnormal expansion of the laryngeal Ventricle. May be confined by the thyroid cartilage (internal laryngocele). May be extend through the cricothyroid membrane into the neck (external laryngocele). Often associated with activities leading to raised intralaryngeal pressureclassically trumpet playing. May occur secondary to a malignancy within the laryngeal ventricle, which must be excluded.

Clinical Findings
Laryngoscopy : smooth swelling of the affected supraglottis; External laryngoceles are also palpable as a smooth, relatively soft anterior triangle mass. CT imaging : characteristic finding of air within the lesion, which may be partially fluid filled.

Treatment
Internal laryngocele may be managed by endoscopic laser surgery; External laryngocele requires a transcervical approach.

SUBGLOTTIC HEMANGIOMAS

Stridor in first 6 months of life. Commonly associated with cutaneous hemangioma. Progression of symptoms from intermittent to persistent. Vascular mass in subglottis. Spontaneous resolution over several years

 Rare approximately 1.5% of all congenital laryngeal anomalies. Can occur in any part of the larynx, subglottis is the most common site. Typically unilateral Can also be circumferential or multiple sites. Vascular hamartomas: most commonly capillary in nature on histologic examination Cavernous or mixed types can also occur.

 About half of patients with a subglottic hemangioma Cutaneous hemangiomas Frequently found in the head and neck region. female : male = 2 : The natural progression of hemangiomas is from an initial proliferative phase to an involutional phase. The proliferative phase starts soon after birth and usually continues for 12 months, after which gradual involution occurs over a period of years. Most hemangiomas will have resolved by the age of 5 years.

Malignant laryngeal lesions

In the United States, 11,000 new cases of larynx cancer e ach year (1% of new cancer diagnoses) One third of these patients will die of their disease. Male-to-female ratio is 4:1 Most prevalent in the sixth and seventh decades of life. More prevalent among lower socioeconomic groups, for whom it is often not diagnosed until more advanced stages.

 More than 90% : squamous cell carcinoma (SCC) and is directly linked to tobacco and excessive alcohol use. Because of the complex and multifaceted nature treatment planning is best delivered through a multidisciplinary tumor board format.

Pathogenesis
More than 90% of patients with larynx cancer have a history of heavy tobacco and alcohol use. Laryngeal infection with the human papillomavirus (HPV)
Papillomatosis (usually benign) Subtypes 16 and 18 are known to degenerate into SCC.

 Relationship with gastroesophageal reflux is still uncertain. Therapies directed at suppressing acid appear to decrease the recurrence of laryngeal cancer. Various occupational exposures and toxic inhalations (such as asbestos and mustard gas), nutritional deficiencies, and previous neck irradiation have all been linked to larynx cancer as well.

 Genes and gene products being investigated for their link to larynx cancer :
P53, the Bcl-2 family of genes other markers of apoptosis:
proliferating cell nuclear antigen (PCNA), Ki67 cyclin D1, the ras gene other oncogenes, tumor suppressor genes, the loss of heterozygosity and changes in the DNA content of tumors.

Epidemiology
Most larynx cancers: arising in the glottis or supralglottis Subglottis cancers: rare extensions of glottis or supralglottis primary cancers Supraglottic larynx richer lymphatic drainage nodal metastases higher clinical stage

Incidence of larynx cancer by site.

Supraglottic40% Glottic59% Subglottic1%

Laryngeal carsinoma

Larynx cancer: incidence of neckmetastases by site.

T1 Supraglottis Glottis Subglottis 1540% < 5% T2 3542% 510% T3 5065% 1020% T4 > 65% 2540% 50% All T 2550%

Staging
TNM (tumor, node, metastasis) system of the American Joint Committee on Cancer. T4 tumors :
resectable (T4a) unresectable (T4b) Stage IV tumors :
IVA, IVB, and IVC (distant metastases present) staging.

based on the 1998 or earlier systems : umbrella T4 and Stage IV designation.

 indicators of the prognosis :

(1) histologic characteristics : extracapsular spread in nodal metastases, angiolymphatic invasion, perineural spread, and a high histologic grade; (2) various chromosomal and molecular markers: p53 mutations, Ki67 or PCNA overexpression, DNA content, and loss of heterozygosity; (3) the presence of comorbidities.

T (tumor), N (nodes), M (metastases), staging for malignant laryngeal disorders

Supraglottis T1 Tumor limited to one subsite of supraglottis T2 Tumor involving more than one adjacent subsite of supraglottis, glottis, or region outside the supraglottis (vallecula, tongue base, medial wall of pyriform sinus) T3 Tumor causes vocal cord fixation and/or invades preepiglottic space, postcricoid area T4a Tumor invades through thyroid cartilage, and/or extends to nonlaryngeal soft tissues of neck T4b Tumor invades prevertebral space or mediastinum, or encases carotid artery

Glottis
T1 Tumor limited to vocal cord; may involve anterior or posterior commissure T2 Tumor extends to supraglottis, glottis, and/or impaired vocal cord mobility T3 Vocal cord fixation T4a Tumor invades through thyroid cartilage, and/or extends to nonlaryngeal soft tissues of neck T4b Tumor invades prevertebral space or mediastinum, or encases carotid artery

Subglottis
T1 Tumor limited to the subglottis T2 Tumor extends to vocal cord with normal or impaired mobility T3 Vocal cord fixation T4a Tumor invades through cricoid or thyroid cartilage, and/or extends to nonlaryngeal soft tissues of neck T4b Tumor invades prevertebral space or mediastinum, or encases carotid artery

 N0 N1 N2a N2b

N2c
N3 M0 M1

No cervical lymph nodes positive Single ipsilateral lymph node 3 cm Single ipsilateral lymph node > 3 cm and 6 cm Multiple ipsilateral lymph nodes, each 6 cm Bilateral or contralateral lymph nodes, each 6 cm Single or multiple lymph nodes > 6 cm No distant metastases Distant metastases present

Stage
I II III IVA IVB IVC

T
T1 T2 T3 T13 T4a T14a T4b any T any T

N
N0 N0 N0 N1 N02 N0 any N N3 any N

M
M0 M0 M0 M0 M0 M0 M0 M0 M1

SYMPTOMS AND SIGNS Hoarseness, dysphagia, hemoptysis, neck mass, throat pain, ear pain, airway compromise, and aspiration. Slightest change in the vocal cord hoarseness: glottic cancers often found at an early stage. Supraglottic cancers typically present at a more advanced stage (tumors are bulkier : higher T stage).

 Supraglottis : richer lymphatic supply metastasize earlier diagnosed at the advanced N stage. Clinical cervical adenopathy : a poor prognosis and advances the overall stage. swallowing difficulties Significant weight loss. Throat and ear pain : symptoms of advancedstage tumors.

PHYSICAL EXAMINATION

1. Laryngoscopy: Indirect laryngoscopy or a fiberoptic endoscope. Malignant lesions : fungating, friable, nodular, or ulcerative, or simply as changes in mucosal color . Careful attention must be paid to the airway status. Direct laryngoscopy (under general anesthesia) definitive examination of tumor extent.

2. Neck examination Enlarged lymph nodes and noting their location, size, firmness, and mobility. Restricted laryngeal crepitus can reveal postcricoid or even retropharyngeal invasion.

SPECIAL TESTS

Biopsy Imaging studies:

chest x-ray Computed tomography (CT) scan Magnetic resonance imaging (MRI) Positron emission tomography (PET) scanning

Histologic Types
A. SQUAMOUS CELL CARCINOMA > 90% of larynx cancers linked to tobacco and excessive alcohol use.

continuum of change

dysplasia

carcinoma in situ

invasive carcinoma

hyperplasia
normal phenotype

Invasive SCC
Well differentiated
Moderately differentiated poorly differentiated and

 SCC can invade blood and lymphatic vessels as well as nerves. Immunohistochemical staining is positive for keratin proteins. Variants of SCC include verrucous carcinoma, spindle cell carcinoma, basaloid SCC, and denosquamous carcinoma.

B. SALIVARY GLAND CANCERS

from the minor salivary glands that line the mucosa of the larynx most common:
Adenoid cystic carcinoma (ACC) Mucoepidermoid carcinoma (MEC)

C. SARCOMAS

Mesenchymal origin. Rarely seen in the larynx. The most common is chondrosarcoma. Most often from the cricoid cartilage.

Treatment
Early-stage larynx cancer (Stages I and II)
either surgery or radiation in single-modality therapy.

Advanced-stage larynx dual-modality therapy cancer (Stages III and IV) with surgery and radiation

most T3 and T4 tumors

total laryngectomy

Radiation therapy
The chief advantage Short-term complications The long-term complications
better voice quality

odynophagia laryngeal edema possibility of laryngeal fibrosis, radionecrosis, hypothyroidism

Adjuvant radiation

should start within 6 weeks of surgery on once-daily protocols lasts 67 weeks

more extensive treated area

mucositis during therapy chronic xerostomia after treatment.

Less common complications

hypothyroidism, radionecrosis, esophageal stricture