1. اول دفتر به نام ایزد یکتا ....

2. MALIGNANT TUMORS OF THE LARYNX AND HYPOPHARYNX
Chapter 99
Department of Oto-Rhino-Laryngolog of Isfahan Medical University

3. INTRODUCTION
similarities between malignant tumors of the larynx and hypopharynx in relationship to etiology
Laryngeal carcinomas are more prevalent in heavy smokers, present earlie
hypopharyngeal carcinomas present late, have a high association with alcoholism and other disorders, and commonly present with cervical metastatic disease.

4. INCIDENCE m/f incidence from 15:1  5:1 in 2004
incidence of hypopharyngeal/larynx tumors :1/3
smoked 40 or more cigarettes daily had an age-adjusted death rate of 15/100,000  0.6/100,000 : among nonsmokers.
Rolled cigarettes are also more dangerous than commercially packaged cigarettes
A recent French study showed a 13-fold increase in laryngeal cancer for smokers, and those consuming more than 1.5 L/day of wine had a 34-fold increased risk

5. RF For larynx tumor Cigarettes and alcohol
Chemical carcinogens : asbestos, nickel compounds, and certain mineral oils
Genetics and susceptibility to:1-secondary primary tumor.2-Aneuploidy  dysplasia to head and neck cancer 3-Genetic alterations of chromosomal region 9p21.4-mutant p53 (suppressive gene )
HPV DNA??
gastroesophageal reflux

6. Risk Factors

7. RF FOR HYPOPHARYNGEAL CANCER
postcricoid carcinoma, (F>M), all forms of hypopharyngeal malignancy M>>F AT: 55 to 70Y
. heavy alcohol ingestion, and heavy smoking
Plummer-Vinson syndrome postcricoid carcinoma
Plummer-Vinson or Paterson-Brown-Kelly Syndrome :dysphagia, hypopharyngeal and esophageal webs, weight loss, and iron deficiency anemia in women aged 30 to 50

8. Second Primary Malignancies
Patients with hypopharynx CA : significant risk of a second primary malignancy OR metachronous malignancy
. The likelihood of a second primary tumor developing for head and neck cancer is 12.8%
The likelihood of a second primary tumor developing increases with time and is 23% at 8 years
all patients with second primary tumor had a history of >50 pack-years of smoking.
The hypopharyngeal area was the third most common site for patients with floor of mouth cancers to have a second primary malignancy

9. HX laryngeal cancers are detected at an earlier
Most patients with hypopharyngeal cancers (70%) manifest stage III disease.
Hypopharyngeal tumors can cause a chronic sore throat, dysphagia, or referred otalgia and are thus managed with antibiotics, because the process is mistakenly attributed to infectious disease.
The rich lymphatic network in the submucosal tissue surrounding the hypopharynx allows early spread

10. ANATOMY AND EMBRYOLOGY
hypopharynx  tracheobronchial primordium (arch 4 or 5) in the midline Fusion
supraglottis  buccopharyngeal primordium (arch 3 or 4) without a midline merger
The supraglottis  superior laryngeal nerve as the nerve of the 3th arch and the superior thyroid artery as its vascular supply.
In contrast, arches 4 and 6 create the glottis and subglottis
the theory : separate derivation explains why supraglottic tumors of substantial bulk do not spread across the laryngeal ventricle to the vocal cord. This region was confirmed as a barrier to tumor spread
Transglottic tumors cross the ventricle and may initiate as supraglottic or glottic cancers. As they enlarge, these tumors fail the compartmentalization thesis by direct mucosal extension or through the paraglottic space.

11. Anatomic regions of the hypopharynx.

12. Diagnosis
educated the public to seek evaluation for hoarseness persisting longer than 4 weeks
Dysphagia& :common symptom of supraglottic or hypopharyngeal ca
refractory asthma without voice change common symptom of subglott ca
DX:Laryngoscopy(vc &biopsy)\CT MRI(LN)

13. Diagnosis of Hypopharyngeal Cancer
hX of heavy alcohol ingestion; heavy smoking;
persistent dysphagia, persistent sore throat, or a foreign body sensation. The average duration : 2 to 4 months.
. A later symptom is referral otalgia
, 20% : asymptomatic neck mass, (ipsilateral, a jugulodigastric or midjugular lymph node )
Radiologic Assessment of the Larynx and Hypopharynx :CT(1-preepiglottic space and paraglottic space involvement 2-Eeosion
Thyroid cartilage destruction :best by CT  total laryngectomy (T4 stage)
MRI using T2-weighted images may be superior to highlight submucosal tumor extension into the preepiglottic and paraglottic spaces

14. Endoscopic Evaluation of the Larynx and Hypopharynx
Cord mobility is best assessed preoperatively.
fixation of the cord is differentiated from arytenoid fixation by palpation of the vocal process and can help stage the disease.
NO flexible esophagogastrostomy &N0 barium swallow
Endoscopy is also required to rule out the existence of a second or concurrent malignancy

15. Assessment of Precancerous Laryngeal Lesions
Biopsy is always needed to confirm the diagnosis,
gross appearance of 1- fungal laryngitis, 2-sarcoidosis,3- tuberculosis, or4- Wegener's granulomatosis can be mistaken for advanced carcinoma
Small suspicious lesions should be completely excised with a border of healthy laryngeal submucosa
large lesions should be adequately sampled with the laryngeal biopsy forceps to measure invasion below the basement membrane
Pseudoepitheliomatous hyperplasia (granular cell myoblastoma) of the supraglottic larynx may be misdiagnosed as carcinoma

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

17. 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

18. 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

19. 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

20. 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

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

23. MANAGEMENT OF PREMALIGNANT LESIONS AND CA IN SITU
five categories with 1-hyperkeratosis, 2-hyperkeratosis with atypia3- carcinoma in situ (CIS)4- superficially invasive carcinoma,5- invasive carcinoma
When :1-hyperkeratosis with atypia and often 2-CIS, TX conservative  strip of cord is removed. :( microscopically removed). F/up and rebiopsy: 6 to 12 W later
Management of precancerous lesions is conservative surgery. : radiotherapy may fail (10%),
Many surgeons believe that unless the patient is unreliable, is a significant risk for repeat GA, or lives far away, radiation is a second choice for this disease

24. MANAGEMENT OF LARYNGEAL CANCER Glottic Cancer
for T1 lesions, surgery 90% to 95% cure rates --_>radiotherapy(cure rates of 75% to 90%.)
Partial surgery(no radiotherapy):
1)decreasing importance vocal cord mobility,
2) subglottic extension,
3) anterior commissure invasion,
4) arytenoid cartilage involvement.
The middle third of vocal fold lesions  endoscopic, laser resection, or open cordectomy. (Cure rates =100% -with good margins _)&95% cure rate for radiotherapy.

25. MANAGEMENT OF Glottic Cancer
50% of radiotherapy failures for T1 glottic cancer failed at the anterior commissure.
Hypomobility of the vocal fold reduces the cure rates and emphasizes the advantage of surgery over radiotherapy
T2 tumors managed by primary radiotherapy showed a 30% local failure rate, which, when surgically salvaged, improved to 94%
T2 lesions classification be divided into T2a and T2b on the basis of mobility. In this analysis, a 70% local control rate was noted for the former category vs 51% in the latter
T2 and early T3 lesions of the glottis have more recently been managed by supracricoid laryngectomy with cricohyoidoepiglottopexy.
cricohyoidoepiglottopexy.= resection of the entire thyroid cartilage and paraglottic spaceThe cricoid cartilage, the hyoid bone, much of the epiglottis and at least one arytenoid cartilage must be conserved.
cricohyoidoepiglottopexy. have satisfactory deglutition, phonation, and 100% decannulation with a 5% local recurrence rate.

26. CRITERIA FOR HEMILARYNGECTOMY FOR RECURRENT CANCER AFTER RADIOTHERAPY
Lesion limited to one cord (may involve the anterior commissure)
Body of arytenoid free of tumor
Subglottic extension no >5 mm
Mobile cord
No cartilage invasion
Recurrence correlating with initial tumor

27. Subglottic Cancer is unusual, with only 1%
located 1 cm below the vocal cord =arise below the conus elasticus
The clinical presentation : airway obstruction;
spread locally  cricoid cartilage and thyroid gland
with lymphatic spread  lower deep jugular nodes, the Delphian node (prelaryngeal), and the paratracheal nodes .
Management requires1) total laryngectomy+2)Ipsilateral thyroidectomy and3) paratracheal node dissection 4) positive nodes or deep invasion, postoperative radiotherapy to include the superior mediastinum is needed to prevent stomal recurrence.
stage T4 or T3 glottic carcinoma  total laryngectomy ipsilateral nodes(in most cases ), =20% risk metastasis

28. Late-Stage Disease
Obstructive laryngeal  premanagement tracheostomy increased local or stomal recurrence
If a tracheostomy is necessary,  surgery within 48 hours+bilateral paratracheal node dissection+ postoperative mantle radiotherapy.
Recurrence at the stoma after laryngectomy is grave extensive penetration
subglottic cancer is most associated with stomal recurrence because the Delphian and paratracheal drainage ports are presumed to be the pathway to recurrence
even aggressive management of stomal recurrence is morbid and often unsuccessful, prevention of recurrence is paramount
risk of infiltration is high, the1) thyroid gland, at least ipsilateral, is removed and2) bilateral paratracheal node dissections are accomplished and3) postsurgical radiation used. includes the upper mediastinum and paratracheal beds.

29. Late-Stage Disease
Hemithyroidectomy or subtotal thyroidectomy is recommended
1- for cases of palpable abnormality,
2-subglottic tumors,
3- or glottic tumors with >1 cm of subglottic extension,
4-T4 glottic tumors, and T4 piriform sinus tumors.
Thyroid function is reduced after larynx cancer management that includes radiotherapy or extensive laryngeal and thyroid surgery depressed and lethargic months after management may be hypothyroid;
Follow-up : at 6 months, 1 year, and when clinically indicated thereafter

30. Supraglottic Cancer
Early supraglottic (epiglottic) tumors, which are suprahyoid, can be grossly excised endoscopically
but infrahyoid tumors do not fare so well with only laser resection endoscopic laser partial laryngectomy
preepiglottic space has been invaded in up to 50% of cases of infrahyoid carcinoma, which cannot be predicted even if CT and physical examination are used.
frequent postoperative x-ray therapy is used for indications at the primary site vs a rare need for this accompanying N0 supraglottic laryngectomy.
more central supraglottic lesions have less metastatic potential than aryepiglottic fold or lateral epiglottic sites

31. Supraglottic Cancer
Limited supraglottic tumors, which are defined as T1 to T3  supraglottic laryngectomy (if the vocal cord is mobile).
Arytenoid involvement allowed partial surgery +complications with swallowing,
Extended resections that  removal of the vallecula and base of the tongue up to the level of the circumvallate papilla
Patient selection for supraglottic laryngectomy is important (Younger, and good pulmonary reserve..)to tolerate the mild-to-moderate aspiration

32. Limitations to supraglottic laryngectomy
Include1) thyroid cartilage invasion or anterior commissure involvement,
2) Involvement of the glottis and vocal cord fixation  paraglottic space invasion are relative contraindications to partial surgery,
3) Cricoid cartilage involvement clearly mandates against a supraglottic laryngectomy, because swallowing is severely impaired with laryngeal preservation and cricoid cartilage resection.
4) Bilateral arytenoid cartilage involvement is an absolute contraindication to supraglottic laryngectomy
Radiotherapy seems to offer less local control than supraglottic laryngectomy
73% 5-year survival after supraglottic surgery actuarial 4-year survival is 50%, and cancer-free survival is 74%

33. EXTENSION OF SUPRAGLOTTIC LARYNGECTOMY
Subtotal laryngectomy with cricohyoidopexy ( a functional laryngectomy) for carcinoma extended to the 1)true vocal cord, the ventricle, 2)involving the thyroid cartilage and the paraglottic space.
The resection includes the entire thyroid cartilage, the paraglottic space, the epiglottis and the entire preepiglottic space. To be successful, the cricoid cartilage, hyoid bone, and at least one arytenoid cartilage must be spared.
Control of the neck is the most important aspect of managing supraglottic tumors, 

34. VARIANTS OF SQUAMOUS CELL CARCINOMA
Verrucous Carcinoma
Pseudosarcoma
Basaloid Squamous Cell Carcinoma

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