MALIGNANT TUMORS OF THE LARYNX Yard.Doc.Dr.Müzeyyen Doğan

Learning goal and objectives of the lesson Learning goal of the lesson: The learner should know the pathophsiological and etiological conditions of the malign disorders of the larynx and their treatments. Learning objectives of the lesson the learner will be able to: list the signs and symptoms of laryngeal neoplasms describe basic principals of laryngeal oncological surgery describe available therapeutic options for laryngeal neoplasms understand how to approach the patient with a mass in larynx

Overview 11,000 new cases of laryngeal cancer per year in the U.S. Accounts for 25% of head and neck cancer and 1% of all cancers One-third of these patients eventually die of their disease Most prevalent in the 6th and 7th decades of life

Overview 4:1 male predilection Downward shift from 15:1 post WWII Due to increasing public acceptance of female smoking More prevalent among lower socioeconomic class, in which it is diagnosed at more advanced stages

Subtypes Glottic Cancer: 59% Supraglottic Cancer: 40% Subglottic Cancer: 1% Most subglottic masses are extension from glottic carcinomas

History The first laryngectomy for cancer of the larynx was performed in 1883 by Billroth Patient was successfully fed by mouth and fitted with an artificial larynx In 1886 the Crown Prince Frederick of Germany developed hoarseness as he was due to ascend the throne.

Crown Prince Frederick of Germany

History Was evaluated by Sir Makenzie of London, the inventor of the direct laryngoscope Frederick’s lesion was biopsied and thought to be cancer He refused laryngectomy and later died in 1888

History Frederick was succeeded by Kaiser Wilhelm II, who along with Otto von Bismark militarized the German Empire and led them into WW I Could an Otolaryngologist have prevented WW I?

Risk Factors

Risk Factors Prolonged use of tobacco and excessive EtOH use primary risk factors The two substances together have a synergistic effect on laryngeal tissues 90% of patients with laryngeal cancer have a history of both

Risk Factors Human Papilloma Virus 16 &18 Chronic Gastric Reflux Occupational exposures Prior history of head and neck irradiation

Histological Types 85-95% of laryngeal tumors are squamous cell carcinoma Histologic type linked to tobacco and alcohol abuse Characterized by epithelial nests surrounded by inflammatory stroma Keratin Pearls are pathognomonic

Histological Types Verrucous Carcinoma Fibrosarcoma Chondrosarcoma Minor salivary carcinoma Adenocarcinoma Oat cell carcinoma Giant cell and Spindle cell carcinoma

Anatomy

Anatomy

Anatomy

Anatomy

Anatomy

Anatomy

Anatomy

Anatomy

Natural History Supraglottic tumors more aggressive: Direct extension into pre-epiglottic space Lymph node metastasis Direct extension into lateral hypopharnyx, glossoepiglottic fold, and tongue base

Natural History Glottic tumors grow slower and tend to metastasize late owing to a paucity of lymphatic drainage They tend to metastasize after they have invaded adjacent structures with better drainage Extend superiorly into ventricular walls or inferiorly into subglottic space Can cause vocal cord fixation

Natural History True subglottic tumors are uncommon Glottic spread to the subglottic space is a sign of poor prognosis Increases chance of bilateral disease and mediastinal extension Invasion of the subglottic space associated with high incidence of stomal reoccurrence following total laryngectomy (TL)

Presentation Hoarseness Most common symptom Small irregularities in the vocal fold result in voice changes Changes of voice in patients with chronic hoarseness from tobacco and alcohol can be difficult to appreciate

Presentation Patients presenting with hoarseness should undergo an indirect mirror exam and/or flexible laryngoscope evaluation Malignant lesions can appear as friable, fungating, ulcerative masses or be as subtle as changes in mucosal color Videostrobe laryngoscopy may be needed to follow up these subtler lesions

Presentation Good neck exam looking for cervical lymphadenopathy and broadening of the laryngeal prominence is required The base of the tongue should be palpated for masses as well Restricted laryngeal crepitus may be a sign of post cricoid or retropharyngeal invasion

Presentation Other symptoms include: Dysphagia Hemoptysis Throat pain Ear pain Airway compromise Aspiration Neck mass

Work up Biopsy is required for diagnosis Performed in OR with patient under anesthesia Other benign possibilities for laryngeal lesions include: Vocal cord nodules or polyps, papillomatosis, granulomas, granular cell neoplasms, sarcoidosis, Wegner’s granulomatosis

Work up Other potential modalities: Direct laryngoscopy Bronchoscopy Esophagoscopy Chest X-ray CT or MRI Liver function tests with or without US PET ?

Staging- Primary Tumor (T) TX Minimum requirements to assess primary tumor cannot be met T0 No evidence of primary tumor Tis Carcinoma in situ

Staging- Supraglottis Tumor limited to one subsite of supraglottis with normal vocal cord mobility T2 Tumor involves mucosa of more than one adjacent subsite of supraglottis or glottis, or region outside the supraglottis (e.g. mucosa of base of the tongue, vallecula, medial wall of piriform sinus) without fixation T3 Tumor limited to larynx with vocal cord fixation and or invades any of the following: postcricoid area, preepiglottic tissue, paraglottic space, and/or minor thyroid cartilage erosion (e.g. inner cortex) T4a Tumor invades through the thyroid cartilage and/or invades tissue beyond the larynx (e.g. trachea, soft tissues of neck including deep extrinsic muscles of the tongue, strap muscles, thyroid, or esophagus) T4b Tumor invades prevertebral space, encases carotid artery, or invades mediastinal structures

Staging- Glottis T1 Tumor limited to the vocal cord (s) (may involve anterior or posterior commissure) with normal mobilty T1a Tumor limited to one vocal cord T1b Tumor involves both vocal cords T2 Tumor extends to supraglottis and/or subglottis, and/or with impaired vocal cord mobility T3 Tumor limited to the larynx with vocal cord fixation and/or invades paraglottic space, and/or minor thyroid cartilage erosion (e.g. inner cortex) T4a Tumor invades through the thyroid cartilage, and/or invades tissues beyond the larynx (e.g. trachea, soft tissues of the neck including deep extrinsic muscles of the tongue, strap muscles, thyroid, or esophagus T4b Tumor invades prevertebral space, encases carotid artery, or invades mediastinal structures

Staging- Subglottis T1 Tumor limited to the subglottis T2 Tumor extends to vocal cord (s) with normal or impaired mobility T3 Tumor limited the larynx with vocal cord fixation T4a Tumor invades cricoid or thyroid cartilage and/or invades tissues beyond larynx (e.g. trachea, soft tissues of the neck including deep extrinsic muscles of the tongue, strap muscles, thyroid, or esophagus) T4b Tumor invades prevertebral space, encases carotid artery, or invades mediastinal structures

Staging- Nodes N0 No cervical lymph nodes positive N1 Single ipsilateral lymph node ≤ 3cm N2a Single ipsilateral node > 3cm and ≤6cm N2b Multiple ipsilateral lymph nodes, each ≤ 6cm N2c Bilateral or contralateral lymph nodes, each ≤6cm N3 Single or multiple lymph nodes > 6cm

Staging- Metastasis M0 No distant metastases M1 Distant metastases present

Stage Groupings Tis N0 M0 I T1 II T2 III T3 T1-3 N1 IVA T4a N0-2 T1-4a Tis N0 M0 I T1 II T2 III T3 T1-3 N1 IVA T4a N0-2 T1-4a N2 IVB T4b Any N Any T N3 IVC M1

Treatment Premalignant lesions or Carcinoma in situ can be treated by surgical stripping of the entire lesion CO2 laser can be used to accomplish this but makes accurate review of margins difficult

Treatment Early stage (T1 and T2) can be treated with radiotherapy or surgery alone, both offer the 85-95% cure rate. Surgery has a shorter treatment period, saves radiation for recurrence, but may have worse voice outcomes Radiotherapy is given for 6-7 weeks, avoids surgical risks but has own complications

Treatment XRT complications include: Mucositis Odynophagia Laryngeal edema Xerostomia Stricture and fibrosis Radionecrosis Hypothyroidism

Treatment Advanced stage lesions often receive surgery with adjuvant radiation Most T3 and T4 lesions require a total laryngectomy Some small T3 and lesser sized tumors can be treated with partial larygectomy

Treatment Adjuvant radiation is started within 6 weeks of surgery and with once daily protocols lasts 6-7 weeks Indications for post-op radiation include: T4 primary, bone/cartilage invasion, extension into neck soft tissue, perineural invasion, vascular invasion, multiple positive nodes, nodal extracapsular extension, margins<5mm, positive margins, CIS margins, subglottic extension of primary tumor.

Treatment Chemotherapy can be used in addition to irradiation in advanced stage cancers Two agents used are Cisplatinum and 5-flourouracil Cisplatin thought to sensitize cancer cells to XRT enhancing its effectiveness when used concurrently.

Treatment Induction chemotherapy with definitive radiation therapy for advanced stage cancer is another option Studies have shown similar survival rates as compared to total laryngectomy with adjuvant radiation but with voice preservation. Role in treatment still under investigation

Treatment Modified or radical neck dissections are indicated in the presence of nodal disease Neck dissections may be performed in patients with supra or subglottic T2 tumors even in the absence of nodal disease N0 necks can have a selective dissection sparing the SCM, IJ, and XI N1 necks usually have a modified dissection of levels II-IV

Surgical Options

Hemilaryngectomy No more than 1cm subglottic extension anteriorly or 5mm posteriorly Mobile affected cord Minimal anterior contralateral cord involvement No cartilage invasion No neck soft tissue invasion

Supraglottic laryngectomy T1,2, or 3 if only by preepiglottic space invasion Mobile cords No anterior commissure involvement FEV1 >50% No tongue base disease past circumvallate papillae Apex of pyriform sinus not invloved

Supracricoid Laryngectomy Resection of true vocal cords, supraglottis, thyroid cartilage Leave arytenoids and cricoid ring intact Half of patients remain dependent on tracheostomy

Total Larygectomy Indications: T3 or T4 unfit for partial Extensive involvement of thyroid and cricoid cartilages Invasion of neck soft tissues Tongue base involvement beyond circumvallate papillae

Total Laryngectomy

Total Laryngectomy

Total Laryngectomy

Total Laryngectomy

Voice Rehabilitation Tracheostomal prosthesis Electrolarynx Pure esophageal speech

Complications Inaccurate staging Infection Voice alterations Swallowing difficulties Loss of taste and smell Fistula Tracheostomy dependence Injury to cranial nerves: VII, IX, X, XI, XII Stroke or carotid “blowout” Hypothyroidism Radiation induced fibrosis

Prognosis 5 year survival Stage I >95% Stage II 85-90% Stage III 70-80% Stage IV 50-60% After initial treatment patients are followed at 4-6 week intervals. After first year decreases to every 2 months. Third and fourth year every three months, with annual visits after that

Prognosis Patients considered cured after being disease free for five years Most laryngeal cancers reoccur in the first two years Despite advances in detection and treatment options the five year survival has not improved much over the last thirty years

References Malignant Tumors of the Larynx and Hypopharynx. Cummings- Otolaryngology- Head and Neck Surgery. 4th ed., Mosby, 2005. Malignant Laryngeal Lesions. Lawani- Current Diagnosis and Treatment in Otolaryngology- Head and Neck Surgery. McGraw-Hill and Lange, 2004. Neck. Moore- Essential Clinical Anatomy. 2nd ed., Lippincott, 2002. Head and Neck. Rohen- Color Atlas of Anatomy. 5th ed., Lippincott, 2002. Surgery for Supraglottic Cancer. Myers- Operative Otolaryngology Head and Neck Surgery Vol. 1. 1st ed., Saunders, 1997. Surgery for Glottic Carcinoma. Myers- Operative Otolaryngology Head and Neck Surgery Vol. 1. 1st ed., Saunders, 1997. The Larynx. Lore and Medina- An Atlas of Head and Neck Surgery. 4th ed., Elsevier, 2005. Hinerman, R, Morris, C, et al. Surgery and Postoperative Radiotherapy for Squamous Cell Carcinoma of the Larynx and Pharynx. Am J Clin Oncol. 2006; 29(6): 613-621. Huang, D, Johnson, C, et al. Postoperative Radiotherapy in Head and Neck Carcinoma with Extracapsular Lymph Node extension and/or Positive Resection Margins: a Comparative Study. Int J Radiat Oncol Biol Phy. 1992; 23:737-742. Bernier, J, Domenge, C, et al. Postoperative Irradiation with or without Concomitant Chemotherapy for Locally Advanced Head and Neck Cancer. N Engl J Med. 2004; 350: 1945-1952. Sessions, D, Lenox, J, et al. Supraglottic Laryngeal Cancer: Analysis of Treatment Results. Laryngoscope. 2005; 115: 1402-1410. Wolf, GT. The Department of Veterans Affairs Laryngeal Cancer Study Group. Induction Chemotherapy Plus Radiation Compared with Surgery Plus Radiation in Patients with Advanced Laryngeal Cancer. New England Journal of Medicine. 1991; 324: 1685-90. Lefebre J, Chevalier D, Luboinski B, Kirkpatrick A, Collette L, Sahmoud T. Larynx Preservation in Pyriform Sinus Cancer: Preliminary Results of a European Organization for Research and Treatment of Cancer Phase III Trial. Journal of the National Cancer Institute. Jul 1996. 88(13): 890-899. Grant’s Atlas 10th ed. CD-ROM