This presentation provides a comprehensive overview of the physiological functions of the larynx. We will examine the intricate mechanics of phonation, the role of the vocal folds in airway protection, and the coordinated muscular actions required for deglutition and effective cough reflexes.

1. METASTATIC NECK
DISEASE
DR SHARADH CHANDRA
PGY2
KOTI ENT

2. INTRODUCTION
● When cancer cells spread to neck lymph nodes its called Neck Metastasis
● The degree of lymph node involvement should be regarded as an indirect index of the
systemic tumour burden
● Cure rates drop in half when there is regional lymph node involvement
● Elective removal of regional lymph nodes serves as a staging procedure for treatment-
surgical and non surgical

3. TUMOUR BIOLOGY - METASTASIS
● Understanding the molecular processes triggering
metastatic cascades in cancers is Advancing.
● Cancer cells access the lymphatic system through pre-
existing vessels
● Solid tumors can induce lymphangiogenesis.
● Vascular endothelial growth factors (VEGF)-C and VEGF-
D produced by cancer cells play an active role in
lymphangiogenesis by binding to VEGF receptor-3 on
lymphatic endothelial cells

4. Metastatic primary tumours have been shown to express distinct signature genes that set them apart from non-
metastatic tumours
This metastatic profile includes genes related to the extracellular matrix, adhesion, motility and protease inhibition.
This is facilitated by three molecular events:
(1) Cellular adhesion molecules - E cadherin downregulation - making the cancer cells free to migrate.
(2) Overexpression of integrins + production of matrix metalloproteinases (MMP 1, 2, 3, 9 and 14) that act upon
the matrix to increased cellular motility.
(3) autocrine and paracrine cytokines, mediated by integrin receptors
genotypic (e.g. p53 and MET oncogene mutation), phenotypic (e.g. E cadherin downregulation)
microenvironmental (e.g. expression of VEGF-C) processes combine to facilitate Metastasis

5. Behaviour Of Disease Within The Cervical Lymph Nodes
Toker described four distinct growth patterns of squamous cell carcinoma
(SCC) within cervical lymph nodes
1.Cancerous deposits in the subcapsular sinus, growth within the affected
node takes place, replacing the architecture of the node before extracapsular
spread occurs.
2.Metastasis infiltrate the lymphatic sinuses (Germinal centres,trabeculae -
intact) -
Ultimately, extracapsular spread occurs by the direct penetration and
destruction of the capsule, or by the arrest of further underlying capsular or
juxtacapsular lymphatics.

6. 3.(less common pattern) - deposition of a malignant embolus within the subcapsular sinus + arrest
of tumour within capsular/juxtacapsular lymphatics. =>cancer growth both within and outside the
node
4.(uncommon metastatic pattern) is where capsular/juxtacapsular emboli grow with no intranodal
cancer.
extracapsular spread - much earlier.
Metastatic involvement of various lymph node regions usually progresses from superior to inferior
but lymph node groups can be bypassed, leading to ‘skip metastases’.
Early contralateral spread is present in tumors which are at midline or near midline

7. Neck Lymph Node Levels
● There are approximately 150
lymph nodes on either side of
the neck
● Size is from 3mm to 3cm but
most nodes are less than
1 centimetre

10. REGION SPECIFIC LYMPHATIC DRAINAGE
REGION LYMPHATIC DRAINAGE
NASOPHARYNX, NASAL CAVITIES &
SINUSES
Retropharyngeal or submandibular LNs →
LEVEL II & III
OROPHARYNX Retropharyngeal nodes → LEVEL II, III, IV
ORAL CAVITY Posterior: IB LEVEL II & III
Anterior: IA LEVEL II, III & IV
Skip metastases(Tongue): LEVEL IV
LARYNX Supraglottis: B/L LEVEL II & III
Subglottis: Prelaryngeal, Pretracheal Or
Paratracheal
Nodes LEVEL III & IV & VI

11. Echelon Nodes
SITE ECHELON LN'S
Oral cavity Levels I, II & III
Larynx & pharynx Levels II, III, IV
Thyroid Levels IV, VI & VII
Parotid Gland Pre-auricular, Periparotid & Intraparotid
LNs
Levels II, III & Va LN
Submandibular & sublingual gland Levels I, II & III

12. METASTATIC BEHAVIOUR IN THE PREVIOUSLY TREATED NECK
Surgery →Collateral lymphatic channels Diverted lymph flow →Contralateral or
Retrograde spread
Radiation therapy →↓Lymphocytes within LNs & Thickening of the walls →
Lymphatic obstruction
Shunting
Contralateral spread
Surgical scar may trap tumor cells which may lead to recurrence

13. METASTATIC NODAL DISEASE
• Level I-lip, anterior tongue, anterior floor of mouth, buccal mucosa
• Level II, III - tonsil, base of tongue (scalp, external auditory canal)
• Level IV - hypopharynx & larynx
• Level V - nasopharyngeal malignancy
• Level VI - thyroid, subglottic

14. ● The nasopharynx, nasal cavities and sinuses- levels II, III & V
● The oropharynx similarly - levels II, III and IV
The oral cavity:
posterior parts of the oral cavity - level II/III or indirectly via the level Ib
More anterior parts of the oral cavity and tongue also drain to these
More anterior parts of the oral cavity and tongue - level II/III + level la or directly to
the jugular nodal chain (levels II to IV).

15. The larynx:
The supraglottis - levels II/III, with a greater tendency for bilateral nodal drainage.
The lower system - levels III/IV through lymphatics which pass through or behind
the cricothyroid membrane and also into the prelaryngeal, pretracheal or
paratracheal nodes (level VI) before reaching the deep cervical nodes.
Vocal cords are relatively avascular, they have an extremely sparse lymphatic
drainage and, as such, lymph node metastases from small carcinomas at this site
are uncommon
The hypopharynx -Drainage is to levels III, IV, VI and VII

16. OCCULT NODAL DISEASE
• Presence of neck metastasis in the neck nodes that cannot be clinically or
radiologically identified-
• 2 categories
1) Occult metastasis that can be identified by the light microscopy
2) Micrometastases less than 2mm that need special histological techniques
(immunohistochemistry, step serial sectioning and molecular analysis) for
identication.
Occult metastasis can only be identified only when it is removed

17. • Lymph node negative in histology means
CANCER NEVER REACHED THE NODE
Or else
IT REACHED BUT WAS DESTROYED IN THE NODE
• This make several controversies in the Management of occult neck disease
• Observational data suggests conversion of N0 to N+ is similar to the incidence of
pathological positive nodes In END specimens (30%)

18. CYSTIC NECK METASTASIS
● usually of oropharyngeal origin,
● most common sites being the tonsil or tongue base.
● Human papillomavirus (HPV) related tumours are more often associated with
cystic metastases than HPV negative tumours.
● These lymph node metastases tend to have a better prognosis than their non-
cystic counterparts.
● reported as branchiogenic carcinoma in the past.
● Given the exponential rise in HPV positive oropharyngeal carcinoma
throughout the world, any cystic level II neck mass in an adult should be
considered as a potential metastasis and should be investigated

19. EXTRANODAL EXTENSION(ENE)
• Associated with a poor prognosis (½ survival rate)
Presence of skin involvement/soft tissue involvement
with deep fixation or tethering to underline muscle/
structures or clinical sign of nerve Involvement
• Increased risk of local recurrence, distant
metastases and early recurrence
• If ENE is detected following surgery add post-
operative radiotherapy or chemoradiation

20. PROGNOSTIC NODAL FEATURES
• Site Size and number
• Low neck nodes
• Extracapsular spread
• Morphology
• Bilateral or contralateral spread

21. FACTORS IMPLICATED IN PATTERN OF METASTATIC NODAL DISEASE
• Tumour size
• Tumour site
• Tumour thickness
• Previous treatment
• Tumour recurrence

22. CLINICAL STAGING (UICC)
• Nx - Regional lymph nodes cannot be assessed
• N0 - No regional lymph node metastasis
• N1-Single ipsilateral node <3cm, ENE -Negative
• N2a-single ipsilateral node 3-6cm
• N2b - Multiple ipsilateral nodes 3-6cm
• N2c-Bilateral or contralateral nodes 3-6cm
• N3a-Node/ Nodes >6cm, ENE -Negative
• N3b-Node/ Nodes >6cm, ENE -positive
They now take into account ENE status and HPV (P16) status, and split the staging into distinct clinical and
pathological classication

23. Joint UICC AJCC classification (extra model extension has poor prognosis; HPV has better prognosis)

26. NECK DISSECTION TERMINOLOGY
A Surgery which removes the lymph node bearing areas of the neck with/without the non-lymphatic
structures - SCM, IJV & accessory nerves
Standardized neck dissection terminology by the American Academy of Otolaryngology and Head and
Neck Surgery in 1991
Updated by the Committee for Neck Dissection Classification of the American Head and Neck Society
in 2002
Neck dissections divided into two broad types with subdivisions:
1. comprehensive (removal of levels I–V)
2. selective (SND) (less than five levels).
Elective neck dissection (END) is any type of neck dissection that is performed on the clinically and
radiologically negative neck (cN0)

27. Classification of neck dissection techniques
TYPE STRUCTURES REMOVED
Radical neck dissection Level (I-V), IJV, SCM, spinal accessory
nerve
Modified radical neck dissection Level I-V
One of non lymphatic is preserved
Type 1: accessory spinal
Type 2: accessory spinal + IJV
Type 3: accessory spinal + IJV + SCM
Selective neck dissection One or more LN level preserved
Extended radical neck dissection Additional LN groups or non lymphatic

28. Selective Neck Dissection (SND)
Supraomohyoid I-III
Extended supraomohyoid (anterolateral) I-IV
Lateral II-IV
Posterolateral II-V
Anterior or central VI (Perithyroid, Delphian, Tracheo-
oesophageal & anteriosuperior
mediastinum)

29. Classification of Neck Dissections
Based on 4 concepts
1. Radical neck dissection RND is the standard basic procedure for cervical
lymphadenectomy against which all other modifications
2. Modifications of the RND which include preservation of any nonlymphatic
structures are referred to as modified radical neck dissection (MRND)
3. Any neck dissection that preserves one or more groups or levels of lymph
nodes is referred to as a selective neck dissection (SND)
4. An extended neck dissection refers to the removal of additional lymph node
groups or non-lymphatic structures relative to the RND

30. SKIN INCISION
• Vascularisation of flaps
• Exposure
• Protection of major vessels
• Localization of primary tumour
• Consider previous radiotherapy & reconstruction
• Cosmesis
• Previous surgical field

31. Blood Supply Of Cervical Neck Skin
Blood enters from above, below and either side with a
resultant watershed in the middle of the neck.
• Incisions can be planned to utilize this so as to maximize
blood supply to each of the neck flaps

33. RADICAL NECK DISSECTION
• Lymph nodes level I - V
• Non-lymphatic structures
• Accessory nerve
• Internal jugular vein
• Sternocleidomastoid muscle

34. Indication: extensive cervical involvement or matted lymph nodes with gross
extracapsular spread and invasion into SAN, IJV, SCM.
Contraindication
• Untreatable primary tumour or unresectable neck disease
• Patient unfit
• Distant metastasis
• Simultaneous bilateral dissection

35. MODIFIED NECK DISSECTION
Medina classification (1989)
• Modified radical neck dissection
- Type I (XI preserved)
- Type II (XI, IJV preserved)
- Type III (XI, IJV, and SCM preserved) (FND)

36. SELECTIVE NECK DISSECTION
• Any type of cervical lymphadenectomy with preservation of one or more lymph
node groups
• Four subtype:
Supraomohyoid neck dissection
Posterolateral neck dissection
Lateral neck dissection
Anterior neck dissection

37. SUPRAOMOHYOID NECK DISSECTION
• Removal of lymph nodes
in regions I-III
• SCC oral cavity (T1-T4) with
• N0
• Single palpable LN in level I
or
• II (controversial) with Ca oral
cavity, lip

39. POSTEROLATERAL NECK DISSECTION
• Removal of levels II-V
• Skin cancer posterior to tragus

40. LATERAL NECK DISSECTION
• Remove lymph nodes in levels II-IV
• Ca larynx, oropharynx, hypopharynx T2-4 N0

41. ANTERIOR NECK DISSECTION
• Removal of LN surrounding the visceral
structure in the anterior aspect of the
neck, level VI
• Differentiated and medullary Ca of
thyroid with thyroidectomy

42. EXTENDED RADICAL NECK DISSECTION
• Removal of additional lymphatic structure & Non lymphatic structure other than
RND
• Retropharyngeal LN
• Level VII LN
• Hypoglossal nerve
• Carotid artery
• Skin of neck

43. GENERAL COMPLICATIONS
• Anaesthetic complications
• Post operative atelectasis with basal collapse
• Pneumonia
• Ischaemic heart disease
• Urinary retention
• Deep vein thrombosis

44. LOCAL COMPLICATIONS
• Hemorrhage
• Wound infection
• Carotid artery rupture
• Nerve injuries
• Chylous fistula
• Pneumothorax
• Cerebral edema

45. ASSESSMENT OF CERVICAL LYMPHADENOPATHY
● Clinical assessment
● Fine needle aspiration cytology
● Ultrasound scan
● Computed Tomography
● Magnetic Resonance Imaging
● Positron Emission Tomography
● Open Biopsy

46. CLINICAL EXAMINATION
● Remains the most important initial method of assessment
● Variable in accuracy (Clinicians experience)
● Sensitivity of 74% specificity of 81% overall accuracy of 77% (Merrit et al)
● Difficult in short stocky necks
● Drawback is nodes may go unnoticed until they reach a considerable size

47. FINE NEEDLE ASPIRATION CYTOLOGY
● Technique is particularly useful in assessment of a palpable node when
searching for a primary
● In the presence of a primary less useful (evidence of HPV or EBV
transcripsts) (HPV oropharynx EBV nasopharynx)
● Easy to perform and quick in reporting
● Overall accuracy >90% (depends on pathologists experience)

48. ULTRASOUND SCAN
● Can detect the presence malignant cervical lymph nodes with sensitivity of
70% to 90%
● When combined with FNAC it increases to 90%
● No absolute criteria to differentiate between malignant vs benign nodes
[absent hilar echoes and increases in short axis length are generally
considered to be features of metastatic neck nodes.]

49. COMPUTED TOMOGRAPHY (C.T.)
• Detection of malignant neck nodes is higher than clinical examination
• Criteria to categorize as metastatic node
1) short axis diameter of 1cm
2) cluster of three or more nodes >0.8cm
3) nodal necrosis or patchy enhancement within nodes
Central Necrosis+Enlarged Nodes+Thin Rim of Inflammation (RIM enhancement)

50. MAGNETIC RESONANCE IMAGING (M.R.I.)
• Meta analysis suggests MRI can detect metastatic neck disease similar to CT
• MRI is better in assessing N0 neck in the presence of deep invasion

51. POSITRON EMISSION TOMOGRAPHY (Ρ.Ε.Τ.)
● Uses 18F-2-fluoro-2-deoxy-D-glucose (FDG) as radioactive tracer
● Can identify the areas of higher glucose uptake
● Anatomical localization difficult
● Coregistered anatomic and functional imaging systems (PET-CT) lead to
accurate image fusion by harvesting advantages of both techniques
● Role in occult primary, recurrent, residual disease & distant metastasis
● Sensitivity - 95 to 98%, Specificity - 95 to 98%
● False positive results are common first few weeks after chemo radiation.Scan
should be deferred for 10 to 12 weeks after completion of treatment

52. OPEN BIOPSY
● In general best avoided as initial diagnostic modality
● When FNAC not available, non diagnostic, results suggesting a lymphoma, or
anaplastic Carcinoma or primary site is occult may be necessary
● Prognosis will not be different if the definitive treatment is done within 6 weeks
● Any incision should made to facilitate to remove the scar via subsequent neck
dissection and vital structures like sternocleidomastoid may have to be
removed due to scar tissue

53. SENTINEL NODE BIOPSY
● Used to assess the presence of occult disease in N0 neck
● Assumption is "If these echelon nodes are negative for tumour deposits rest
of the neck is free of tumour metastasis"
● Technique uses radioactive probes and/or blue dye around tumour then first
to third echelon nodes identified using gamma cameras or peri-operative
hand held probes.
● The nodes thus identified are then sent for biopsy
● Melanoma, breast & other non head and neck tumours

54. TREATMENT OF METASTATIC NECK DISEASE
Decided by the stage of neck disease
General principles of neck spread
● Untreated neck patterns of spread is predictable
● In occult neck metastasis usually found at first echelon LN Region. This
permits principle of Selective Neck Dissection.
● Previous Treatment alters the pattern of spread
● Patients with palpable neck nodes likely to have non palpable spread in other
levels

55. N0 NECK
Historically evaluation and treatment for N0 is great dilemma and still controversial
Whether to treat or not to treat
Number of Treatment options
● Elective surgery
● Elective radiotherapy
● Wait and watch
● Elective neck investigations

57. INDICATIONS FOR ELECTIVE NECK TREATMENT
• 15% to 20% chance of subclinical neck disease
• Vigilant follow up not possible
• Clinical evaluation of the neck is difficult
• Access to the neck for reconstruction

58. CHOICE OF TREATMENT MODALITY FOR N0
• Elective neck dissection and irradiation are equally effective
• Choice dictated by many factors
Patient and surgeons choices
quality of life issues and how the primary is treated

59. THE CONTRALATERAL N0 NECK
• Incidence of occult metastases: 30-70%
• Supraglottic, Hypopharyngeal & Oropharyngeal Tumors
• Contralateral neck treatment is warranted

60. ARGUMENTS FOR ELECTIVE NECK SURGERY
• High incidence of occult metastatic disease
•Selective Neck Dissection got low morbidity and mortality
• Routine follow up will not detect the earliest conversion from No to N+
• Untreated neck mets can induce distant metastasis
• Elective neck surgery can be performed at primary surgery
• Patient compliance for regular follow ups cannot be assured
• Presence of multiple occult metastasis will dictate adjuvant irradiation

61. ARGUMENTS AGAINST ELECTIVE NECK SURGERY
• Careful clinical follow up combined with imaging has the potential to detect early
conversion
• Control rates no lower than when wait and watch policy is followed
• Elective surgery result in inevitable morbidity
• Elective Neck Dissection removes the natural barrier to the spread
• Elective Neck Dissection creates a scarred hypoxic field that can reduce the
radiation kill

62. THE N+ NECK (N1 NECK)
● Treatment modality is usually dictates by treatment to primary site
● Primary treated with Surgery → MRND (1)
● Primary treated with Radiation Neck—>Irradiation
● Upstaging after pathological assessment—>Adjuvant Radiotherapy
● Chemoradiation followed by Neck Dissection (Residual disease)
● In palpable neck disease all 5 LN levels should be dissected
● Majority of the cases accessory nerve can be preserved (MRND)

65. INDICATIONS OF POSTOPERATIVE RADIOTHERAPY
• Extracapsular spread
• Two or more positive nodes
• N2 N3 Stages
• Residual disease

66. N2A AND N2B NECK
• MRND sparing spinal accessory nerve where possible
• PORT(Totally implantable venous access device) is indicated
Primary treated with Surgery—>Comprehensive neck dissection
Adjuvant RT (success rate ↑10%)
• Adjuvant chemo-radiation in ENE
Primary treated with RT→ Residual—>Salvage surgery

67. N2C NECK
• Common primary site is tongue base, supraglottic larynx and hypopharynx
• Earlier it was considered as grave prognosis
• Now evidence shows the size number and the ECS determines the prognosis
rather than the laterality
• If operable (Radical neck dissection + conservative neck dissection on less
involved site)+ adjuvant radiotherapy
• Chemo-radiation

68. N3 NECK (MASSIVE NODES)
● Commonly fixed to skin or underlying structures
● High risk for distant metastasis -----PET CT may be warranted
● Mostly incurable
● Decision depends on stage of disease, presence or absence of fixation and
structure to which node is fixed, surgeon experience

69. ● Long term control is poor and the benefit of treatment should be carefully
weighed against morbidity
● Radical treatment is warranted in patients who have less advanced primary
● Fixation to mandible, SCM, midline muscles -------treatable
● Fixation to brachial plexus or skull base: contraindication to surgery
● Fixation to the skin may be treated by wide resection and flap repair
● Arterial invasion -------careful assessment
● RND OR ERND + chemoradiation
● MANY PATIENTS PALLIATION WILL BE THE BEST OPTION

70. NECK METASTASIS FROM UNKNOWN PRIMARY
● Unknown or occult primary carcinoma
● Presentation of metastatic neck lymphadenopathy without the development of
a primary lesion within a subsequent five year period.
● Failure to identify occult primary-
Spontaneous regression of primary tumour
Autoimmune destruction
Accelerated tumour progression

71. Metastatic carcinoma with no evidence of primary site after history, physical
examination and radiological imaging.
Secondary of neck<10% of all unknown primary
Most likely head and neck primary site: tonsil (45%), base of tongue (40%) and
piriform fossa (10%).

73. Unknown Primary treatment
T0N1M0
Single modality treatment (neck dissection or radiotherapy)
T0N2M0 AND T0N3M0
Neck dissection + adjuvant chemo-radiation

74. TREATMENT OUTCOMES
Nodal Status Recurrence rate/Failure rate
N0 3%-7%
N1 10%
N2 20–30%
N3 85%

75. Management of recurrence
Unresectable Re-irradiation +/- Chemotherapy
Resectable Wide Resection + Post op RT
Ipsilateral untreated neck Neck Dissection +/- Post op RT
RT+ Salvage surgery
Contralateral untreated neck Salvage surgery
Previously treated neck Radical radiotherapy (if primary was
surgery)
Salvage Surgery (if primary was radiation)
Recurrence after combination treatment Wide excision of the tumor & the overlying
skin + Flap reconstruction + Brachytherapy

76. Reference
Scott-Brown’s Otorhinolaryngology Head and Neck Surgery VOLUME 3
Stell and Maran’s Textbook of Head and Neck Surgery and Oncology