The document discusses metastatic neck disease in head and neck cancer. It covers the natural history and evaluation of neck disease, including the levels and regions of cervical lymph nodes. It also discusses factors that affect the probability of cervical metastases based on primary tumor site and stage. Additionally, it summarizes the drainage patterns of different head and neck primary sites and describes investigations used to evaluate neck disease.

1. Metastatic neck disease
One of the most important prognostic factors in head &neck cancer is the presence or absence ,
level& size of metastatic neck disease.
Natural history &evalution of neck disease
The factors are which affect natural history of neck disease are
Tumour site;
Tumour size;
Tumour thickness;
Previous recurrence;
Tumour history;
Tumour immunology.
Perineural & perivascular invasion,the degree of tumour differtiation.
It is possible to predict the site of a primary tumour based upon the distribution of cervical
metastases.A number of levels or regions within neck which contain groups of lymph nodes
representing the first echelon sites for metastatic head –neck primary sites.
Level I ;Ia ,submental &Ib, submandibular lymph node,
Level II; Upper jugular chain above the level of the hyoid bone.IIa is anterior to accessory nerve& IIb
posterior to the accessory nerve.
Level III; middle jugular chain nodes from the level of the hyoid bone to the level of the cricoids.
LevelIV;lower jugular chain nodes from the level of the cricoids to the suprasternal notch.
Level V; posterior triangle lymph nodes, can be divided into Va above the level the of the
omohyoid,& Vb below the level of the omohyoid.
Level VI; Central compartment lymph nodes;
Level VII; superior mediastinal nodes.
Retropharyngeal & paraphyngeal nodes are not classified in these levels.
It is important to realize that the above drainage patterns apply to the nontreated neck.
An incision in the neck for a lymph node biopsy can altered patterns of lymphatic drainage for up to
one year following surgery. Further shunting of lymph with opening opening up of abnormal
channels occurs when more extensive surgery & radiotherapy is undertaken,& once a lymph node is
palpable & contains tumour there may be shunting of cells to the contralateral neck.

2. The probability of cervical metastases (N) related to primary (T) staging in patients with head &neck
cancer.
Primary site T-stage N0% N1% N2-3%
Floor of mouth T1 89% 9 2
Oral tongue T1 86 10 4
Retromolar
T1 88 2 9
trigone,anterior
faucial pillar
Nasopharynx T1 8 11 82
Soft palate T1 92 0 8
Base of tongue T1 30 15 55
Tonsilar fossa T1 30 41 30
Supraglottic
larynx
Hypopharynx
T1
T1
61
37
10
21
29
42
Organ specific drainage
The nasopharynx ,nasal cavities & sinuses drain via the junctional nodes into the upper deep cervical
nodes (levels II & III), having passed through retropharyngeal or submandibular lymph nodes.
Oropharynx similarly drains into the upper & middle deep cervical nodes, again either directly or via
the retropharyngeal or submandibular nodes.
Total lymph node in the body 500, & 200 of these are in the head & neck. The normal range in size is
from 3mm to 3cm but most nodes are less than a centimetre.
The jugulodigastric node(low-level II or high-levelII) is situated within the triangle formed by the
internal jugular vein, facial vein ,&posterior belly of digastrics muscle.Receives lymph from
submandibular region, the oropharynx & oral cavity.
The jugulo-omohyoid nodes(low-levelII or high level IV) where omohyoid crosses the internal vein,
Receives lymph from anterior floor of mouth, oropharynx, larynx.
Laryngeal drainage is separated into upper & lower systems at the level of the true vocal cords.

3. Supraglottis drains (Upper syetem) via thyroid membrane to reach the deep cervical nodes (levels
II/III).
The lower system drains directly via cricothyroid membrane to reach the deep cervical nodes (levels
III/IV).Behind the cricothyroid membrane drain into the prelaryngeal , pretracheal or paratracheal
nodes.
The first echelon of lymph node for oral cavity I,II,III.
The first echelon of lymph node for larynx & pharynx II,III,IV.
The first echelon of lymph node submandibular & sublingual I,II,III.
The first echelon of lymph node parotid preparotid,paraparotid.intraparotid.
The first echelon of lymph node for thyroid VI(trachea-oeshopheal groove) & IV.
Tumour biology:
Once squamous cells carcinoma is established within the lymphatic system,tumour growth is difficult
to arrest.Other reports that the regional lymph node are involved in effective tumourlysis.One
important question need to be resolved is if there is any benefit treating the regional lymphatic
basin early (N0) ,or later on in the disease process(N+).
Cancer cells gain access to the lymphatic system from the tumour periphery through gaps between
the lymphatic endothelial cells.Then passive transport to the regional lymph node within lymph.The
afferent lymphatic join the marginal sinus in the cortex of lymph nodes,so that cellular division
occurs first periphery in the cortex & TUMOUR MIGRATION can then occur to involve the medulla.
Once tumour cells arrive at a draining lymph node, they can proliferate, die, remain dormant, or
enter the circulation through nodal blood vessels.A number of important properities have recently
been assigned to tumour cells or metastatic seeds & these include cell growth
,chemotaxis,immunological, metabolic & hormonal factors.Similar host environment (soil factors)
include tissue & stromal environmental, hormonal ,inflammatory & immunological response& the
presence or absence of vital nutrients.
From lymph node, 1)efferent channels leave the hilum to join the terminal collecting trunks (Right &
left lymphatic ducts) then drainage is into venous system.
2)cancer cells can gain access the bloodstream entering directly from a node
3) alternatively lymph node may be completely bypassed through collateral channels
& this mechanism is enhanced by local obstruction due to metastasis ,reactive hyperplasia,&sinus
histiocytosis.This is called skip metastases.
Regional lymph node have a reasonable constant holding capacity & above that threshold ,all other
tumour cells pass to efferent channels & then into the general circulation.Lymph node are not
simple mechanical barrier but involved in conferring anti-tmour immunity,some lymphocyte are
cytotoxic to cancer cells.

4. Molecular method for the detection of metastases
Molecular assays are estimated to be over 500 more times more sensitive than histological methods
for detection of cancer cells.
1) Tumour specific p53 mutations
2) Oligonucleotide-mediated mismatch ligation assay for detection of cancer cells in
histologically negative regional lymph node in colorectal & lung cancer.
3) Recently, mitochondrial DNA mutations ,identification of these mutations in regional lymph
nodes may have potential for molecular staging in the future.
Patients with positive lymph nodes in head & neck cancer have approximately a 50% decreased
chance of survival when compared with those who are node negative.
This philosophy is now being questioned with regard to locoregional discase being cured with local
treatments (surgery & radiation),since distant metastasis are now a significant problem.Locoregional
controlled patient may die more frequently of second primaries or distant metastases.overall
survival has not changed.
The main arguments for prophylactic elective node treatment assumes that regional lymph node
are not only effective barriers to tumour ,but also represent further sources of disease dissemination
with regard to distant metastases.It Is now well recognized that metastatic lesions do have the
ability to metastasize.
Tumour metastasis
Tumour metastasis is a complex process which involves many different interaction between the
tumour & its host & influenced by a number of humoral factors endocrine, cellular,metabolic
&nutritional factors.
Treatment modalities can effect tumour-host equilibrium in unpredictable ways & these include the
following:
1)Surgery 2)chemotherapy3)radiotherapy4) trauma5) wound infection.
Surgery can alter the locoregional tumour environment, collateral channels form,alter patterns of
lymphatic metasatic spread & divert lymph flow to the contralateral neck.
Surgical scarring can trap tumour cells, leads to established local recurrence.
Extracapsular nodal spread
There is a general consensus that the presence of extracapsular spread outside a lymph node is
associated with a poor prognosis.Extracapsular spread due to increase in tumour burden or an
increase in tumour aggressiveness or may indicate the presence of a depressed host-immune
response.

5. Extracapsular spread are at increased risk of local recurrence ,distant metastases, & the time to
recurrence is shorter.In presence of extracapsular spread decrease survival rate by approximately
half compared with patients whose tumour was confined to the node.
In addition , postoperative radiotherapy doesnot appear to improve the outcome of patients with
extracapsular spread & have suggested that some form of systemic adjuvant therapy(chemotherapy)
is required as well, although this has not been of proven use in increasing locoregional control,
decreasing the incidence of distant metastases or improving overall survival.
Retropharyngeal nodes
The presence of retropharyngeal nodes with a very poor prognosis.Tumours that are associated with
these nodes include primary disease of the oropharynx,paranasal sinuses & pyriform sinus as well as
advanced primary tumour at any site together with massive unilateral or bilateral neck disease due
to shunting from obstructed lymphatic ducts or channels.
A new designation in the tumour node metastases TNM staging system N4/stageV
N4A represent Retropharyngeal lymph node positive without cervical lymphadenopathy.
N4B represent retropharyngeal lymph node positive with cervical lymphadenopathy.
MRI more accurate than CT scan to assess the retropharyngeal nodes.
Predictors for distant metastases
The overall five year survival rates are reduced by at least 50% when cervical nodes are positive &
reason for that is an aggressive primary tumour & its ability to metastases.The incidence of distant
metastases is related the size of the primary tumour,the presence of neck disease, & overall stage.
Another important finding is that the incidence of distant metastases increases by 50% when there
is recurrent disease present either at primary site or in the neck.
Prognostic nodal features
There are number of features of cervical lymph nodes which indicate a poor prognosis:
1) Site ,size& number
2) Level(low level& multiple level)
3) Extracapsular extension
4) Morphology(these include lymphocyte predominate &sinus histocytosis)
5) Laterality (,bilateral & contralateral disease)
Involvement of low level nodes & noncontiguous or multiple sites was associated a worse prognosis.

6. Criticism of the current staging system
The most important prognostic factors are the number of nodes involved& the presence of
extracapsular spread.
Bilateral lymph node particularly if they are N1 donot carry any worse prognosis than unilateral N1
nodes at certain sites (supraglottis).For other sites contralateral or bilateral nodes carry a dismal
prognosis as such deserve an N3 grouping.
Finally massive nodes on both side of the neck which is often fixed & almost universally fatal don’t
have independent classification.
Investigations
CT :There is no doubt that CT scanning can detect malignant cervical lymphadenopathy within neck.
The detection of malignant disease is based on the fact that a cancer invades the lymph node,Its
size, shape & characteristic change so that as it enlarges ,its centre dies, & appears necrotic & there
is a thin rim of inflammation around edge which shows up on scanning as rim enhancement.
The range of non-malignant cervical lymph node 3mm to 3cm, but greater than 1cm in size on CT
may contain metastatic disease. All nodes greater than 1 cm in size as containing malignant disease,
except those in the low level II high level III region when a 1.5 cm size criterion is often applied.
The two most difficult area in imaging head &neck region are the detection of low-volume neck
disease, residual & recurrent disease following surgery & irradiation.
CT or MRI should definiately be considered ,
1) If neck is being scanned as part of primary tumour assessment.
2) High chance of occult disease >20%
3) In the presence of significant ipsilateral disease when the presence of deep fixation or
contralateral spread may management from surgery to no treatment at all.
4) To assess the difficult neck;
5) Staging prior to non surgical treatment
6) For restaging.
MRI
Can detect cervical lymphadenopathy with similar accuracy rates to CT.However MRI may be better
in evaluating the N0 neck.
USG
USG useful in assessing of the carotid artery & jugular vein by lymph node metastases.

7. PET
We can assess the metabolic activity of cervical lymph nodes using 18 fluorodeoxyglucose. But poor
sensitivity & specificity for low volumne disease.CT/PET is confined to detect occult primary &
assessment of residual & recurrent disease following surgery &irradiation.
FNAC
The possibility of anaplastic carcinoma Or lymphoma usually makes a tru-cut or open biopsy
mandatory.
Open biopsy
Where FNAC not available, equivocal, or nondiagnostic or results suggest either a lymphoma Or
anaplastic carcinoma.An incision should be made to facilitate the removal of the scar via a
subsequent standard neck dissection.
Sentinel node biopsy;
Much attention has given non-head &neck melanoma ,breast cancer,Technique is injection of
radionuclide at the primary site & the patient is then imaged to identify the first lymph node that is
involved in the drainage of a tumour within the primary lymphatic basin of a N0 neck.Due to skip
metastases , & collateral channels are often present.So no role of sentinel node biopsy in head
&neck cancer.