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

2. 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

3. 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

4. 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

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

6. 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.

7. Crown Prince Frederick of Germany

8. 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

9. 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?

10. Risk Factors

11. 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

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

13. 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

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

15. Anatomy

16. Anatomy

17. Anatomy

18. Anatomy

19. Anatomy

20. Anatomy

21. Anatomy

22. Anatomy

23. 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

24. 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

25. 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)

26. 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

27. 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

28. 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

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

30. 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

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

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

34. 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

35. 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

36. 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

37. 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

38. Staging- Metastasis M0 No distant metastases M1
Distant metastases present

39. 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

40. 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

41. 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

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

43. 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

44. 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.

45. 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.

46. 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

47. 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

48. Surgical Options

49. 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

50. 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

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

52. 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

53. Total Laryngectomy

54. Total Laryngectomy

55. Total Laryngectomy

56. Total Laryngectomy

57. Voice Rehabilitation Tracheostomal prosthesis Electrolarynx
Pure esophageal speech

58. 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

59. 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

60. 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

61. 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):
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:
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:
Sessions, D, Lenox, J, et al. Supraglottic Laryngeal Cancer: Analysis of Treatment Results. Laryngoscope. 2005; 115:
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:
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 (13):
Grant’s Atlas 10th ed. CD-ROM