Lip and Oral Cavity

Primary Site(s)
The oral cavity extends from the skin-vermilion junction of the lips to the junction of the
hard and soft palate above, to the line of circumvallate papillae below, and to the anterior
tonsillar pillars laterally. It is additionally divided into multiple specific sites listed below.
Mucosal Lip
The lip begins at the junction of the vermilion border with the skin and includes only the
vermilion surface or that portion of the lip that comes into contact with the opposed lip.
The remainder of the vermillion is staged using the skin chapter . It is subdivided into an
upper and lower lip, joined at the commissures of the mouth.
Buccal Mucosa
The buccal mucosa includes all the mucous membrane lining of the inner surface of the
cheeks and lips from the line of contact of the opposing lips to the line of attachment of
mucosa of the alveolar ridge (upper and lower) and pterygomandibular raphe.
Lower Alveolar Ridge
The lower alveolar ridge refers to the mucosa overlying the alveolar process of the mandible,
which extends from the line o f attachment of m ucosa in the lower gingivobuccal sulcus
to the line of attachment of free mucosa o f the floor of the mouth. Posteriorly, it extends to
the ascending ramus of the mandible.
Upper Alveolar Ridge
The upper alveolar ridge refers to the mucosa overlying the alveolar process of the maxilla,
which extends from the line of attachment of mucosa in the upper gingivobuccal sulcus to
the junction o f the hard palate. Its posterior margin is the upper end o f the pterygopalatine
arch.
Retromolar Gingiva (Retromolar Trigone)
The retromolar gingiva, or retromolar trigone, is the attached mucosa overlying the
ascending ramus of the mandible from the level of the posterior surface of the last lower
molar tooth
to the apex superiorly, adjacent to the tuberosity of the maxilla.
Floor of the Mouth
The floor o f the mouth is a crescentic surface overlying the mylohyoid and hyoglossus
muscles, extending from the inner surface of the lower alveolar ridge to the undersurface
of the tongue. Its posterior boundary is the base of the anterior pillar of the tonsil. It is
divided into two sides by the frenulum of the tongue and harbors the ostia of the
submandibular and sublingual salivary glands.
Hard Palate
The hard palate is the semilunar area between the upper alveolar ridge and the mucous
membrane covering the palatine process o f the maxillary palatine bones. It extends from
the
inner surface of the superior alveolar ridge to the posterior edge o f the palatine bone.
Anterior Two-Thirds of the Tongue (Oral Tongue)
The anterior two-thirds o f the tongue is the freely mobile portion o f the tongue that
extends anteriorly from the line of circumvallate papillae to the undersurface of the tongue
at
the junction with the floor o f the mouth. It is composed of four areas: the tip, the lateral
borders, the dorsum, and the undersurface (nonvillous ventral surface o f the tongue). The
undersurface of the tongue is considered a separate category by the World Health
Organization (WHO).

Regional Lymph Nodes

In general, cervical lymph node involvement from oral cavity primary sites is predictable and
orderly, spreading from the primary to upper, then middle, and subsequently lower cervical
nodes. Any previous treatment o f the neck,through surgery or radiation, may alter normal
lymphatic drainage patterns and result in unusual dissemination of disease to the cervical
lymph nodes. Cancer of the lip, with a low metastatic risk, initially involves adjacent
submental and submandibular nodes, then jugular nodes.Cancers of the hard palate likewise
have a low metastatic potential and involve buccinator, pre-vascular facial and
submandibular, jugular and, occasionally, retropharyngeal nodes. Other oral
cancers spread primarily to submandibular and jugular nodes and uncommonly to posterior
triangle/supraclavicular nodes. Cancer of the anterior oral tongue may occasionally spread
directly to lower jugular nodes. The closer the primary is to the midline, the greater the
propensity for bilateral cervical nodal spread. Although patterns o f regional lymph node
metastases are typically predictable and sequential, disease in the anterior oral cavity also
may spread directly to bilateral or mid-cervical lymph nodes.
Metastatic Sites : the lungs are the most common site o f distant metastases; skeletal and
hepatic metastases occur less often.
Mediastinal lymph node metastases are considered distant metastases, except level VII
lymph nodes (anterior
superior mediastinal lymph nodes cephalad o f the innominate artery).

Major Salivary Glands

Primary Site(s)
The major salivary glands include the parotid, submandibular, and sublingual glands .Tumors
arising in minor salivary glands (mucus-secreting glands in the lining membrane of the upper
aerodigestive tract) are staged according to the anatomic site of origin (e.g., oral cavity,
sinuses, etc.).Primary tumors o f the parotid constitute the largest proportion of major
salivary gland tumors. The parotid is a paired gland that constitutes the majority o f the
salivary gland tissue and thus harbors the majority o f salivary gland tumors, although the
majority are benign. Submandibular glands also are paired and lie on the mylohyoid muscle
anteriorly and the hyoglossus muscle posteriorly. Relatively more malignancies arise in the
submandibular glands than the parotids. Sublingual primary cancers are rare and may be
difficult to distinguish with certainty from minor salivary gland primary tumors o f the
anterior floor o f the mouth.
Regional Lymph Nodes : Regional lymphatic spread from salivary gland cancer varies
according to the histology and size o f the primary tumor. Most nodal metastases will be
clinically apparent on initial evaluation. Low-grade tumors rarely metastasize to regional
nodes, whereas the risk of regional spread is substantially higher from high-grade cancers.
Regional dissemination tends to be orderly, progressing from intraglandular to adjacent
(periparotid, submandibular) nodes, then to upper and midjugular nodes, apex of the
posterior triangle (level VA) nodes, and occasionally to retropharyngeal nodes. Bilateral
lymphatic spread is rare.
Metastatic Sites : Distant metastatic spread is most frequently to the lungs.

Nasopharynx
Primary Site(s)
The pharynx is divided into three regions: nasopharynx, oropharynx, and hypopharynx.
The specific anatomic site of nasopharynx and regional lymphatics are described in
this section. The nasopharynx begins anteriorly at the posterior choana and extends along
the plane of the airway to the level of the free border of the soft palate. It includes the
superior wall, the posterior wall, and the lateral walls, which include the fossae of
Rosenmuller and the mucosa covering the torus tubaris forming the Eustachian tube orifice.
The floor is the superior surface of the soft palate. The posterior margins of the choanal
orifices and o f the nasal septum are included in the nasal fossa. Nasopharyngeal tumors
extending to the nasal cavity or oropharynx in the absence o f parapharyngeal space
involvement do not have a significantly worse outeome than tumors confined to the
nasopharynx. Involvement o f the parapharyngeal space is defined as posterolateral
infiltration from the nasopharynx beyond the buccopharyngeal fascia into the triangular
space lateral to the pharynx.
Regional Lymph Nodes
Nasopharyngeal carcinoma often presents with early lymphatic spread. The retropharyngeal
nodes and the cervical nodes (both jugular and spinal accessory chains) are involved,
often bilaterally. The lymphatic spread in NPC follows a predictable and orderly pattern from
upper to lower neck; “skip” metastasis is rare. In clinical evaluation, the maximum dimension
(in any direction) of the nodal mass, the laterality, and the lowest level of neck involvement
should be assessed. Midline nodes are considered ipsilateral nodes. Nodal size larger than 6
cm in greatest dimension and/or extension below the caudal border of the cricoid cartilage
are associated with the worst prognosis.
Metastatic Sites
Nasopharyngeal carcinoma is notorious for a high risk of distant metastasis. The most
common sites include lung, bone, liver, and distant lymph nodes. Involvement of lymph
nodes below the clavicle (including mediastinum, infraclavicular region, axilla, or groin) is
considered as distant metastases.

HPV-Mediated (p16+) Oropharyngeal Cáncer

Primary Site(s)
The oropharynx is the portion of the continuity of the pharynx extending from the plane of
the superior surface of the soft palate to the superior surface of the hyoid bone (or
vallecula). It includes the base of the tongue, including the lingual tonsil; the inferior
(anterior) surface of the soft palate and the uvula; the anterior and posterior tonsillar pillars
with the palatine tonsils; the glossotonsillar sulci; and the lateral and posterior
pharyngealwalls. HPV-mediated cancers most commonly arise in the lymphatic tissue of the
palatine and lingual tonsil but may arise in any of the regions of the oropharynx.
Regional Lymph Nodes
Oropharyngeal cancers usually involve upper and midjugular lymph nodes and (less
commonly) submental/submandibular nodes. Base-of-tongue cancers commonly manifest
bilateral lymphatic drainage. Unknown primary (TO) nodal positive disease should be
staged using this section if a node is p l6 + and no primary site is identified.
Metastatic Sites
The most common site of distant metastasis is the lung followed by bone.

Oropharynx (p16-) and Hypopharynx

Primary Site(s)
Cancers arise in the mucosa of the oropharynx and hypopharynx. They invade into
neighboring structures as they advance.
Oropharynx
The oropharynx is the portion o f the continuity o f the pharynx extending from the plane o f
the superior surface of the soft palate to the superior surface o f the hyoid bone (or
vallecula). It includes the base of the tongue, the inferior (anterior) surface of the soft palate
and the uvula, the anterior and posterior tonsillar pillars, the glossotonsillar sulci, the
pharyngeal tonsils, and the lateral and posterior pharyngeal walls.
Hypopharynx
The hypopharynx is that portion o f the pharynx extending from the plane o f the superior
border of the hyoid bone (or vallecula) to the plane corresponding to the lower border of
the cricoid cartilage. It includes the pyriform sinuses (right and left), the lateral and posterior
hypopharyngeal walls, and the postcricoid region. The postcricoid area extends from the
level o f the arytenoid cartilages and connecting folds to the plane of the inferior border of
the cricoid cartilage. It connects the two pyriform sinuses, thus forming the anterior
wall o f the hypopharynx. The pyriform sinus extends from the pharyngoepiglottic fold to the
upper end o f the esophagus at the lower border o f the cricoid cartilage and is bounded
laterally by the lateral pharyngeal wall and medially by the lateral surface o f the
aryepiglottic fold and the arytenoid and cricoid cartilages. The posterior pharyngeal wall
extends from the level o f the superior surface of the hyoid bone (or vallecula) to the inferior
border of the cricoid cartilage and from the apex o f one pyriform sinus to the other.
Regional Lymph Nodes
The risk of regional nodal spread from cancers of the pharynx is high. Oropharyngeal cancers
usually involve upper and midjugular lymph nodes and (less commonly)
submental/submandibular nodes. Base of tongue cancers often manifest bilateral
lymphatic drainage. Hypopharyngeal cancers spread to adjacent parapharyngeal,
paratracheal, and mid- and lower jugular nodes. Bilateral lymphatic drainage is common. In
clinical evaluation, the maximum size of the nodal mass should be measured. Midline nodes
are considered ipsilateral nodes. Superior mediastinal lymph nodes are considered regional
lymph nodes (level VII). In addition to the components to describe the N category, regional
lymph nodes should also be described according to the level of the neck that is involved.
Metastatic Sites
The lungs are the most common site o f distant metastases; skeletal or hepatic metastases
occur less often. Mediastinal lymph node metastases are considered distant metastases,
except level Vil lymph nodes.
Nasal Cavity and Paranasal Sinuses
Primary Site(s)
The location and the extent of the mucosal lesion within the maxillary sinus have prognostic
significance. Historically, a plane connecting the medial canthus of the eye to the angle
of the mandible, represented by Ohngren's line, is used to divide the maxillary sinus into an
anteroinferior portion (infrastructure), which is associated with a good prognosis, and a
posterosuperior portion (suprastructure), which has a poor prognosis. The poorer outeome
associated with suprastructure cancers refleets early invasion by these tumors to critical
structures, including the orbit, skull base, pterygoid plates, and infratemporal fossa.
For the purpose o f staging, the nasoethmoidal complex is divided into two sites: nasal cavity
and ethmoid sinuses. The ethmoids are further subdivided into two subsites: left and right,
separated by the nasal septum (perpendicular piate of ethmoid). The nasal cavity is divided
into four subsites: the septum, floor, lateral wall, and the edge of naris to mucocutaneous
junction.
Regional Lymph Nodes
Regional lymph node spread from cancer o f nasal cavity and paranasal sinuses is relatively
uncommon. Involvement of buccinator, prevascular facial, submandibular, upper jugular,
and (occasionally) retropharyngeal nodes may occur with advanced maxillary sinus cancer,
particularly those extending beyond the sinus walls to involve adjacent structures,
including soft tissues of the cheek, upper alveolus, palate, and buccal mucosa or overlying
skin. Ethmoid sinus cancers are less prone to regional lymphatic spread. When only one
side of the neck is involved, it should be considered ipsilateral. Bilateral spread may occur
with advanced primary cancer, particularly with spread o f the primary beyond the midline.
Metastatic Sites
Distant spread usually occurs to lungs, but occasionally there is spread to bone.

Larynx
Primary Site(s)
The following anatomic definition of the larynx allows classification of carcinomas arising in
the encompassed mucous membranes but exeludes cancers arising on the lateral or
posterior pharyngeal wall, pyriform fossa, postcricoid area, or base of tongue. The anterior
limit o f the larynx is composed o f the anterior or lingual surface o f the suprahyoid
epiglottis, the thyrohyoid membrane, the anterior commissure, and the anterior wall o f the
subglottic region, which is composed o f the thyroid cartilage, the cricothyroid membrane,
and the anterior arch of the cricoid cartilage. The posterior and lateral limits include the
laryngeal aspect o f the aryepiglottic folds, the arytenoid region, the interarytenoid space,
and the posterior surface o f the subglottic space, represented by the mucous membrane
covering the surface of the cricoid cartilage. The superolateral limits are composed o f the tip
and the lateral borders of the epiglottis. The inferior limits are made up of the plane passing
through the inferior edge o f the cricoid cartilage. For purposes of this clinical stage
classification, the larynx is divided into three regions: supraglottis, glottis, and subglottis. The
supraglottis is composed o f the epiglottis (both its lingual and laryngeal aspeets),
aryepiglottic folds (laryngeal aspect), arytenoids, and ventricular bands (false cords). The
epiglottis is divided for staging purposes into suprahyoid and infrahyoid portions by a plane
at the level of the hyoid bone. The inferior boundary of the supraglottis is a horizontal plane
passing through the lateral margin o f the ventricle at its junction with the superior surface
of the vocal cord. The glottis is composed o f the superior and inferior surfaces o f the true
vocal cords, including the anterior and posterior commissures. It occupies a horizontal plane
1 cm in thickness, extending inferiorly from the lateral margin o f the ventricle. The
subglottis is the region extending from the lower boundary of the glottis to the lower margin
of the cricoid cartilage.
Regional Lymph Nodes
The risk o f regional metastasis generally is related to the T category. The incidence and
distribution o f cervical nodal metastases from cancer o f the larynx vary with the site of
origin and the T category o f the primary tumor. The true vocal cords are nearly devoid of
lymphatics, and tumors limited to the glottis alone rarely spread to regional nodes.
By contrast, the supraglottis has a rich and bilaterally interconnected lymphatic network, so
primary supraglottic cancers commonly are accompanied by regional lymph node spread.
Advanced glottic tumors may spread directly to adjacent soft tissues, to prelaryngeal,
pretracheal, paralaryngeal, and paratracheal nodes, as well as to upper,
mid, and lower ju g u la r nodes. Supraglottic tumors commonly spread to upper and
midjugular nodes, considerably less commonly to submental or submandibular nodes, and
occasionally to retropharyngeal nodes. The rare subglottic primary tumors spread first to
adjacent soft tissues and prelaryngeal, pretracheal, paralaryngeal, and paratracheal nodes,
then to mid and lower ju g u la r nodes. Contralateral lymphatic spread is common. Any
previous manipulation to the neck, through surgery or radiation, may alter normal lymphatic
drainage patterns, resulting in unusual distribution o f regional spread of disease to the
cervical lymph nodes.
Metastatic Sites
Distant spread is common only for patients who have bulky regional lymphadenopathy.
When distant metastases occur, spread to the lungs is most common; skeletal or hepatic
metastases occur less often. Mediastinal lymph node metastases are considered distant
metastases, except Level Vil lymph nodes (in the anterior superior mediastinum, cephalad to
the innominate artery).

Mucosal Melanoma of the Head and Neck

Primary Site(s)
MMs occur throughout the mucosa o f the upper aerodigestive tract. For a description of
anatomy, refer to the appropriate anatomic site chapter based on the location o f the
mucosal melanoma (e.g., paranasal sinus and oral cavity). MM originates from benign
intramucosal melanocytes that reside in the mucosa o f the upper aerodigestive tract
(paranasal sinuses, oral cavity, pharynx, and larynx). There is no T0 category for MM,
because melanoma of unknown primary is unlikely to arise from the mucosal surfaces and
far more likely to arise from skin.
Regional Lymph Nodes
The cervical nodes are the primary lymphatic drainage, and those at risk are in the basin that
corresponds to the anatomic site where the tumor arises. Due to the rarity o f the disease,
the role of nodal metastasis is confined to either present (N+) or absent (NO). At this time,
the role of extranodal extension (ENE) is unknown and this modifier is not incorporated
intothe system for MM.Metastatic Sites
Distant metastases are common at some point in the course of the disease. The most
common sites are lung and liver.

Cutaneous Squamous Cell Carcinoma of the Head and Neck

Primary Site(s)
CSCC and other carcinomas can occur any where on the skin. CSCC and BCC most commonly
arise on anatomic sites that have been exposed to sunlight.6 CSCC can also arise in skin that
was previously scarred or ulcerated, that is, at the sites of burns and chronic ulcers (chronic
inflammation). All of the components of the skin (epidermis, dermis, and adnexal
structures) can give rise to malignant neoplasms. Nonaggressive NMSC, such as BCC, usually
grow solely by local extension, both horizontally and vertically. Continued local extension
may result in growth into deep structures, including adipose tissue, cartilage, muscle, and
bone. Perineural extension is a particularly insidious form of local extension, as this is often
clinically occult. If neglected for an extended length o f time, nodal metastasis can occur with
otherwise nonaggressive NMSC. Aggressive NMSC, including CSCC and some types of
sebaceous and eccrine neoplasms, also grow by local lateral and vertical extension early in
their natural history. Once deeper extension occurs, growth may become discontinuous,
resulting in deeper local extension, in-transit metastasis, and nodal metastasis. In more
advanced cases, CSCC and other tumors can extend along cranial foramina through the skull
base into the cranial vault. Uncommon types o f NMSC vary considerably in their propensity
for metastasis.
Regional Lymph Nodes When deep invasion and eventual metastasis occurs, local
and regional lymph nodes are the most common sites of metastasis. Nodal metastasis
usually occurs in an orderly manner, initially in a single node, which expands in size.
Eventually, multiple nodes become involved with metastasis. Metastatic disease may spread
to secondary nodal basins, including contralateral nodes when advanced. Uncommonly,
nodal metastases may bypass a primary nodal basin.
Metastatic Sites
Nonaggressive NMSC more often involves deep tissue by direct extension than by
metastasis. After metastasizing to nodes, CSCC may spread to visceral sites, including lung.
Unlike most other forms of cancer, the majority of deaths from CSCC (81 %) appear to result
from uncontrolled loco-regional recurrence, rather than from distant organ metastasis.
LUNG
Cancers Staged Using This Staging System: This classification applies to carcinom as of the
lung, including non-sm all cell and small cell carcinom as, and bronchopul-
monary carcinoid tumors. This classification does not apply to sarcom as or other rare tum
ors o f the lung.

ANATOMY
Primary Site(s)
For the purpose of TNM classification, the lungs are not paired organs but a single organ.
Basically, they are formed by the bronchi and the lung parenchyma. Lung cáncer is a
bronchogenic neoplasm arising from the epithelial cells of the bronchial mucosa or from the
cells lining the alveoli. The right lung has three lobes— upper, middle, and lower— with
three, two, and five segments, respectively. The left lung has two lobes— upper and lower—
with five and four segments, respectively. The segment is considered the smallest anatomic
unit of the lung. Although all lung cancers may be located in any part of the lung, squamous
cell and small cell carcinomas tend to arise from the mucosa of the more central bronchi,
involving the lobar origins and the main bronchi. This central location often causes bronchial
obstruction and atelectasis, either lobar or complete. The natural progression of these
central tumors is to invade the bronchial wall and the mediastinal structures, such as the
pericardium, the phrenic nerve, the superior vena cava, and more rarely, the esophagus, the
aorta, and the heart. On the other hand, adenocarcinomas tend to lócate in the periphery of
the lung, with extensión to the visceral pleura, often causing pleural dissemination and
malignant pleural effusion, and to the chest wall. The earlier adenocarcinomas, such as
adenocarcinoma in situ and minimally invasive adenocarcinoma, also tend to be located
peripherally. The fact that lung lesions do not generate pain and that lung compliance allows
tumors to grow within the lung parenchyma accounts for the late diagnosis of the disease.
Only when the tumor causes bronchial obstruction and subsequent atelectasis, pneumonía
or dyspnea, bleeding from the bronchial mucosa, or pain due to invasión of the parietal
pleura, do patients present with symptoms, and the diagnostic process begins. A high index
of suspicion is needed to avoid minimizing the nonspecific symptoms and attributing them to
benign diseases.

Regional Lymph Nodes

Spread to the regional lymph nodes is a common feature in lung cáncer. The natural
progression from the primary tumor to the intrapulmonary, hilar, mediastinal, and
supraclavicular lymph nodes is not found in every patient with lung cáncer and nodal disease.
Some patients have mediastinal nodal disease without intrapulmonary or hilar nodal
involvement, which is referred to as skip metastases.

Metastatic Sites
Although any organ may be the site of metástasis from primary lung cáncer, the brain,
bones, adrenal glands, contralateral lung, liver, pericardium , kidneys, and subcutaneous
tissue are the most common sites of metastatic spread. In the absence of specific clinical
findings, the staging process should focus on ruling out metástasis in these common sites.