Oral Cavity and Mucosal Lip (ICD-O-4, C00.3-5, C02-06)
The classification applies only to carcinomas (excluding carcinomas of minor salivary glands) of the mucosal surfaces of the lips and of the oral cavity. (For vermillion border of the lip, see page 138)
There should be histological confirmation of the disease.
Anatomical Sites and Subsites
Oral Cavity including Mucosal Lip (ICD-O-4C00.3-5, C02.0-C02.3, C02.9, C03-C06)
- Buccal mucosa
a) Mucosa of upper and lower lips (C00.3-5)
b) Cheek mucosa (C06.0)
c) Retromolar areas (C06.2)
d) Buccoalveolar sulci, upper and lower (vestibule of mouth) (C06.1) - Upper alveolus and gingiva (upper gum) (C03.0)
- Lower alveolus and gingiva (lower gum) (C03.1)
- Hard palate (C05.0)
- Tongue
a) Dorsal surface and lateral borders anterior to circumvallate papillae (anterior two-thirds) (C02.0, 1)
b) Inferior (ventral) surface (C02.2) - Floor of mouth (C04)
The dry lip and vermillion border of the lip (C00.0, C00.1, C00.2) and commissure (C00.6) are included in skin of the head and neck (page 138).
Base of tongue/lingual tonsil C02.4), posterior to circumvallate papillae, is classified in the oropharynx.
The regional lymph nodes are the cervical nodes.
Clinical TNM Classification
T – Primary Tumour
- cTX Primary tumour cannot be assessed
- cT0 No evidence of primary tumour
- cTis Carcinoma in situ
- cT1 Tumour 2 cm or less in greatest dimension and 5 mm or less depth of invasion
- cT2 Tumour 2 cm or less in greatest dimension and more than 5 mm depth of invasion or Tumour more than 2 cm but not more than 4 cm in greatest dimension and depth of invasion not more than 10 mm
- cT3 Tumour more than 2 cm but not more than 4 cm in greatest dimension and depth of invasion more than 10 mm or Tumour more than 4 cm in greatest dimension and not more than 10 mm depth of invasion
- cT4a Tumour more than 4 cm in greatest dimension and more than 10 mm depth of invasion or Tumour invades through the cortical bone (with involvement of spongiosa/spongy bone) of the mandible or maxilla or involves the maxillary sinus, or invades the skin of the face
- cT4b Tumour invades masticator space, pterygoid plates or skull base, or encases
internal carotid artery
Superficial erosion alone of bone/tooth socket by gingival primary is not sufficient to classify a tumour as cT4a.
Superficial invasion of adjacent skin (i.e., dry vermillion and vermillion border of the lip) from mucosal lip is not sufficient to be classified as a T4a tumour.
N – Regional Lymph Nodes
- cNX Regional lymph nodes cannot be assessed
- cN0 No regional lymph node metastasis
- cN1 Metastasis in a single ipsilateral lymph node, 3 cm or less in greatest dimension without clinical extranodal extension
- cN2 Metastasis described as:
- cN2a Metastasis in a single ipsilateral lymph node more than 3 cm but not more than 6 cm in greatest dimension without clinical extranodal extension
- cN2b Metastasis in multiple ipsilateral lymph nodes, not more than 6 cm in greatest dimension, without clinical extranodal extension
- cN2c Metastasis in bilateral or contralateral lymph nodes, not more than 6 cm in greatest dimension, without clinical extranodal extension
- cN3a Metastasis in a lymph node more than 6 cm in greatest dimension without clinical extranodal extension
- cN3b Metastasis in a single or multiple lymph nodes with clinical extranodal extension
Clinical extranodal extension is defined as the presence of skin involvement or soft tissue invasion with deep fixation to underlying muscle or adjacent anatomical structures or clinical signs of nerve involvement. Imaging is becoming a standard method of detecting unequivocal extranodal extension.
Midline nodes are considered ipsilateral nodes.
M – Distant Metastasis
- cM0 No distant metastasis
- cM1 Distant metastasis
Pathological TNM Classification
The pT categories correspond to the clinical cT categories.
Histological examination of a selective neck dissection specimen should ordinarily include six or more lymph nodes. Histological examination of a radical or modified radical neck dissection specimen should ordinarily include 15 or more lymph nodes.
- pNX Regional lymph nodes cannot be assessed
- pN0 No regional lymph node metastasis
- pN1 Metastasis in a single ipsilateral lymph node, 3 cm or less in greatest dimension without pathological extranodal extension
- pN2 Metastasis described as:
- pN2a Metastasis in a single ipsilateral lymph node, 3 cm or less in greatest dimension with pathological extranodal extension or Metastasis in a single ipsilateral lymph node, more than 3 cm but not more than 6 cm in greatest dimension without pathological extranodal extension
- pN2b Metastasis in multiple ipsilateral lymph nodes, none more than 6 cm in greatest dimension, without pathological extranodal extension
- pN2c Metastasis in bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension, without pathological extranodal extension
- pN3a Metastasis in a lymph node more than 6 cm in greatest dimension without pathological extranodal extension
- pN3b Metastasis in a single lymph node more than 3 cm in greatest dimension with pathological extranodal extension or Metastasis in multiple ipsilateral, or any contralateral or bilateral node(s) with pathological extranodal extension
Pathological extranodal extension (pENE) should only be diagnosed when tumour that is present within the confines of a lymph node definitively transgresses through the entire thickness of the lymph node capsule into the surrounding connective tissue, with or without stromal reaction.
A soft tissue deposit should be considered as at least one lymph node with extranodal extension if it occurs at a site where a regional lymph node would be expected.
Stage
| Stage | T | N | M |
|---|---|---|---|
| Stage 0 | Tis | N0 | M0 |
| Stage I | T1 | N0 | M0 |
| Stage II | T2 | N0 | M0 |
| Stage III | T3 | N0 | M0 |
| T1, T2, T3 | N1 | M0 | |
| Stage IVA | T4a | N0, N1 | M0 |
| T1, T2, T3, T4a | N2 | M0 | |
| Stage IVB | Any T | N3 | M0 |
| T4b | Any N | M0 | |
| Stage IVC | Any T | Any N | M1 |
Prognostic Factors Grid – Oral Cavity
| Prognostic factors | Tumour related | Host related | Environment related* |
|---|---|---|---|
| Essential | TNM Surgical resection margin Lymphovascular invasion |
Performance status Smoking during radiotherapy |
Distance from treatment centre Access to specific investigations and/or treatments Socioeconomic status |
| Additional | Tumour budding, tumour hypoxia, lymph node ratio, extensive perineu-ral invasion Worst pattern of invasion PD-L1 status Tumour grade Perineural invasion |
Age, co-morbidity, Betel or areca nut chewing | Expertise of a treatment at the specific level (e.g., surgery or radiotherapy) Access to information R status after surgery |
Salivary gland (ICD-O-4C00-C14, C15.0, C15.3, C30-C33, C41.1)
The definitions of the T, N and M categories are new and are expected to correspond
with the AJCC 9th version.
The classification applies only to carcinomas of the salivary glands. There should be histological confirmation of the disease.
Anatomical Sites Include
- Parotid gland (C07.9)
- Submandibular (submaxillary) gland (C08.0)
- Sublingual gland (C08.1)
- Minor salivary glands (C00-C06, C09-14, C15.0, C15.3, C30-33, C41.1)
The regional lymph nodes are the cervical nodes.
Clinical TNM Classification
T – Primary Tumour
- cTX Primary tumour cannot be assessed
- cT0 No evidence of primary tumour
- cTis Carcinoma in situ
- cT1 Tumour 2 cm or less in greatest dimension without extraparenchymal extension
- cT2 Tumour more than 2 cm but not more than 4 cm in greatest dimension without extraparenchymal extension
- cT3 Tumour more than 4 cm, or gross extraparenchymal or adjacent site mucosal/soft tissue extension beyond site without structural involvement
- cT4a Tumour invades immediately adjacent structures, including skin, bone**, cartilage, solid organ parenchyma, oesophagus, trachea, and/or named nerve
- cT4b Tumour invades beyond adjacent structures, e.g. encasement of carotid artery, and/or base of skull invasion (except nasopharynx), and/or spinal column invasion, and/or intracranial invasion, and/or orbital apex, and/or prevertebral space, and/or mediastinal structures, and/or masticator space, etc.
Extraparenchymal extension is clinical or macroscopic evidence of invasion of soft tissues or nerve, except those listed under T4a and T4b. Microscopic evidence alone does not constitute extraparenchymal extension for classification purposes.
Destruction of intrinsic sinus bones is not considered bone invasion for skull base tumors. Erosion of cortical bone is not considered bone invasion; a minor salivary gland tumor arising within the bone is not considered bone invasion.
N – Regional Lymph Nodes
- cNX Regional lymph nodes cannot be assessed
- cN0 No regional lymph node metastasis
- cN1 Metastasis in 1–3 ipsilateral lymph node(s) without unequivocal imaging-detected or clinical extranodal extension
- cN2 Metastasis in more than 3 lymph nodes or any lymph node with unequivocal imaging-detected and/or clinical extranodal extension
Extranodal extension can be detected clinically or radiologically. Imaging- detected extranodal extension (iENE) on appropriate morphological imaging refers to unequivocal radiologic signs of tumour invasion through the capsule of a lymph node into either perinodal fat or adjacent tissues (e.g. skin, muscle or neurovascular structures) or a coalescent nodal mass (A coalescent nodal mass comprises ≥2 adjacent lymph nodes that have lost their intervening tissue planes and capsules to merge into a single indivisible structure).
Clinical extranodal extension is defined as the presence of skin involvement or soft tissue invasion with deep fixation to underlying muscle or adjacent anatomical structures or clinical signs of nerve involvement. Imaging- detected unequivocal extranodal extension is becoming standard.
Midline nodes are considered ipsilateral nodes.
M – Distant Metastasis
- M0 No distant metastasis
- M1 Distant metastasis
pTNM Pathological Classification
The pT categories correspond to the clinical cT categories.
pN – Regional Lymph Nodes
Histological examination of a selective neck dissection specimen should ordinarily include 10 or more lymph nodes. Histological examination of a radical or modified radical neck dissection specimen should ordinarily include 15 or more lymph nodes. Negative pathological examination of fewer lymph nodes is acceptable for pN0 designation.
- pNX Regional lymph nodes cannot be assessed
- pN0 No regional lymph node metastasis
- pN1 Metastasis in 1–3 lymph node without definitive pathological extranodal extension
- pN2 Metastasis in >3 lymph nodes or Metastasis in any lymph node with definitive pathological extranodal extension
Pathological extranodal extension (pENE) should only be diagnosed when tumour that is present within the confines of a lymph node definitively transgresses through the entire thickness of the lymph node capsule into the surrounding connective tissue, with or without stromal reaction.
A soft tissue deposit should be considered as at least one lymph node with extranodal extension if it occurs at a site where a regional lymph node would be expected.
Stage
| Stage | T | N | M |
|---|---|---|---|
| Stage 0 | Tis | N0 | M0 |
| Stage I | T1 | N0 | M0 |
| Stage II | T2 | N0 | M0 |
| Stage IIIA | T3, T4 | N0 | M0 |
| T1, T2 | N1 | M0 | |
| Stage IIIB | T1, T2 | N2 | M0 |
| T3, T4 | N1, N2 | M0 | |
| Stage IV | Any T | Any N | M1 |
Prognostic Factors Grid – Salivary Glands
Prognostic factors for salivary gland tumour survival
| Prognostic factors | Tumour related | Host related | Environment related* |
|---|---|---|---|
| Essential | Histologic aggression type and grade Tumour size Local invasion Perineural invasion Surgical resection margin |
Age | Distance from treatment centre Access to specific investigations and/or treatments Socioeconomic status |
| Additional | Nodal metastases Molecular markers |
Facial palsy, pain |
Expertise of a treatment at the specific level (e.g., surgery or radiotherapy) Access to information R status after surgery |
Pharynx
The classification applies only to carcinomas (excluding carcinomas of minor salivary glands). There should be histological confirmation of the disease.
Anatomical Sites and Subsites
Nasopharynx (C11):
- Posterosuperior wall: extends from the level of the junction of the hard and soft palates to the base of the skull (C11.0, 1)
- Lateral wall: including the fossa of Rosenmüller (C11.2)
- Inferior wall: consists of the superior surface of the soft palate (C11.3).
The margin of the choanal orifices, including the posterior margin of the nasal septum, is included with the nasal fossa.
Oropharynx (ICD-O- 4C01, C02.4, C05.1-2, C09.0-1, 9, C10.0, C10.2-3, C10.9):
- Anterior wall (glossoepiglottic area)
a) Base of tongue (posterior to the vallate papillae or posterior third) (C01)
b) Vallecula (C10.0)
c) Lingual Tonsil (C02.4) - Lateral wall (C10.2)
a) Tonsil (C09.9)
b) Tonsillar fossa (C09.0) and tonsillar (faucial) pillars (C09.1)
c) Glossotonsillar sulci (tonsillar pillars) (C09.1) - Posterior wall (C10.3)
- Superior wall
a) Inferior surface of soft palate (C05.1)
b) Uvula (C05.2)
Hypopharynx (C12, C13):
- Piriform sinus (C12.9): extends from the pharyngoepiglottic fold to the upper end of the oesophagus. It is bounded laterally by the thyroid cartilage and medially by the hypopharyngeal surface of the aryepiglottic fold (C13.1) and the arytenoid and cricoid cartilages.
- Pharyngo- oesophageal junction (postcricoid area) (C13.0): extends from the level of the arytenoid cartilages and connecting folds to the inferior border of the cricoid cartilage, thus forming the anterior wall of the hypopharynx.
- Posterior pharyngeal wall (C13.2): extends from the superior level of the hyoid bone (or floor of the vallecula) to the level of the inferior border of the cricoid cartilage and from the apex of one piriform sinus to the other.
The regional lymph nodes are the cervical nodes.
Clinical TNM Classification
Nasopharynx (C11)
T – Primary Tumour
- cTX Primary tumour cannot be assessed
- cT0 No evidence of primary tumour, but EBV- positive (EBV- associated) cervical node(s) metastasis present
- cTis Carcinoma in situ
- cT1 Tumour confined to nasopharynx or Tumour extends to oropharynx and/or nasal cavity without parapharyngeal involvement
- cT2 Tumour with extension to parapharyngeal space or Tumour infiltration of the medial pterygoid, lateral pterygoid and/or prevertebral muscles
- cT3 Tumour invades bony structures of skull base, cervical vertebrae, pterygoid structures and/or paranasal sinuses
- cT4 Tumour with any of the following:
- Intracranial extension
- Unequivocal clinical and/or radiological involvement of cranial nerves
- Involvement of hypopharynx
- Invading orbit (including inferior orbital fissure)
- Involvement of parotid gland
- Infiltration beyond the anterolateral surface of the lateral pterygoid muscle
N – Regional Nodes
- cNX Regional lymph nodes cannot be assessed
- cN0 No regional lymph node metastasis
- cN1 Unilateral metastasis in cervical lymph node(s), and/or unilateral or bilateral metastasis in retropharyngeal lymph nodes, and 6 cm or less in greatest dimension, and above the caudal border of cricoid cartilage, and without advanced clinical/radiological extranodal extension
- cN2 Bilateral metastasis in cervical lymph nodes, and 6 cm or less in greatest dimension, and above the caudal border of cricoid cartilage, and without advanced clinical/radiological extranodal extension
- Metastasis in cervical lymph node(s) greater than 6 cm in greatest dimension or Extension below the caudal border of cricoid cartilage or Advanced clinical/radiological extranodal extension
Advanced radiological and/or clinical extranodal extension is unequivocal evidence of tumour invasion into adjacent structures (i.e., skin, muscle, salivary gland and/or neurovascular bundles) identified by appropriate morphological imaging or clinical examination. Midline nodes are considered ipsilateral nodes.
The pT, pN, and pM1 categories correspond to the cT, cN, and cM1 categories. Extranodal extension however is defined pathologically not clinically or radiologically. As treatment for the primary is invariably non- surgical pT category is rarely appropriate
M – Distant Metastasis
- cM0 No distant metastasis
- M1 Distant metastasis.
- M1a Distant metastasis. Three or fewer lesion(s) in one or more organs
- M1b Distant metastasis of more than three lesions in one or more organs
Stage – Nasopharynx
| Stage | T | N | M |
|---|---|---|---|
| Stage 0 | Tis | N0 | M0 |
| Stage IA | T1, T2 | N0 | M0 |
| Stage IB | T0, T1, T2 | N1 | M0 |
| Stage II | T0, T1, T2 | N2 | M0 |
| T3 | N0, N1, N2 | M0 | |
| Stage III | T4 | Any N | M0 |
| Any T | N3 | M0 | |
| Stage IVA | Any T | Any N | M1a |
| Stage IVB | Any T | Any N | M1b |
Oropharynx – HPV Associated
T – Primary Tumour
- cT0 No evidence of primary tumour, but p16 positive (HPV- associated) cervical node(s) metastasis present
- cT1 Tumour 2 cm or less in greatest dimension
- cT2 Tumour more than 2 cm but not more than 4 cm in greatest dimension
- cT3 Tumour more than 4 cm in greatest dimension or extension to lingual surface of epiglottis
- cT4 Tumour invades any of the following: larynx**, deep/extrinsic muscle of tongue (genioglossus, hyoglossus, palatoglossus and styloglossus), medial or lateral pterygoid muscle, hard palate, mandible, pterygoid plates (medial and/or lateral), nasopharynx, skull base, encases carotid artery
The anatomical structure of the tonsillar crypts and lingual tonsil means that the basement membrane is incomplete and no carcinoma in situ is recognised.
Mucosal extension to lingual surface of epiglottis from primary tumours of the base of the tongue and vallecula does not constitute invasion of the larynx.
N – Regional Lymph Nodes
- cNX Regional lymph nodes cannot be assessed
- cN0 No regional lymph node metastasis
- cN1 Metastasis in ipsilateral lymph node(s), all 6 cm or less in greatest dimension, without unequivocal imaging- detected and/or clinical extranodal extension
- cN2 Metastasis in ipsilateral lymph node(s), all 6 cm or less in greatest dimension, with unequivocal imaging- detected and/or clinical extranodal extension or Contralateral or bilateral metastasis in lymph node(s), all 6 cm or less in greatest dimension without unequivocal imaging- detected and/or clinical extranodal extension
- cN3 Metastasis in lymph node(s) greater than 6 cm in greatest dimension or Contralateral or bilateral metastasis in lymph node(s) with unequivocal imaging- detected and/or clinical extranodal extension
Imaging- detected extranodal extension (iENE) on appropriate morphological imaging refers to unequivocal radiologic signs of tumour invasion through the capsule of a lymph node into either perinodal fat or adjacent tissues (e.g. skin, muscle or neurovascular structures) or a coalescent nodal mass, which comprises ≥2 adjacent lymph nodes with loss of their intervening tissue planes and capsules to merge into a single indivisible structure.
Clinical extranodal extension is defined as per Oral Cavity and Mucosal Lip on page 20.
Midline nodes are considered ipsilateral nodes.
M – Distant Metastasis
- M0 No distant metastasis
- M1 Distant metastasis
Oropharynx – HPV Independent
T – Primary Tumour
- cTX Primary tumour cannot be assessed
- cT0 No evidence of primary tumour
- cTis Carcinoma in situ
- cT1 Tumour 2 cm or less in greatest dimension
- cT2 Tumour more than 2 cm but not more than 4 cm in greatest dimension
- cT3 Tumour more than 4 cm in greatest dimension or extension to lingual surface of epiglottis
- cT4a Tumour invades any of the following: larynx,* deep/extrinsic muscle of tongue (genioglossus, hyoglossus, palatoglossus and styloglossus), medial pterygoid, hard palate, mandible
- cT4b Tumour invades any of the following: lateral pterygoid muscle, pterygoid plates, nasopharynx, skull base; or encases carotid artery
Mucosal extension to the lingual surface of epiglottis from primary tumours of the base of the
tongue and vallecula does not constitute invasion of the larynx.
Hypopharynx
T – Primary Tumour
- cTX Primary tumour cannot be assessed
- cT0 No evidence of primary tumour
- cTis Carcinoma in situ
- cT1 Tumour limited to one subsite of hypopharynx (see pages 24 and 25) and 2 cm or less in greatest dimension
- cT2 Tumour invades more than one subsite of hypopharynx or an adjacent site or Tumour measures more than 2 cm but not more than 4 cm in greatest dimension, without fixation of hemilarynx
- cT3 Tumour more than 4 cm in greatest dimension or Tumour with fixation of hemilarynx or Tumour with extension to oesophageal mucosa
- cT4a Tumour invades any of the following: thyroid/cricoid cartilage, hyoid bone, thyroid gland, oesophagus beyond the mucosa, central compartment soft tissue
- cT4b Tumour invades prevertebral fascia, encases carotid artery or invades mediastinal structures
Central compartment soft tissue includes prelaryngeal strap muscles and subcutaneous fat.
Midline nodes are considered ipsilateral nodes.
Oropharynx – HPV Independent and Hypopharynx
N – Regional Nodes
- cNX Regional lymph nodes cannot be assessed
- cN0 No regional lymph node metastasis
- cN1 Metastasis in a single ipsilateral lymph node, 3 cm or less in greatest dimension without clinical extranodal extension
- cN2 Metastasis described as:
- cN2a Metastasis in a single ipsilateral lymph node more than 3 cm but not more than 6 cm in greatest dimension without clinical extranodal extension
- cN2b Metastasis in multiple ipsilateral lymph nodes, none more than 6 cm in greatest dimension, without clinical extranodal extension
- cN2c Metastasis in bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension, without clinical extranodal extension
- cN3a Metastasis in a lymph node more than 6 cm in greatest dimension without clinical extranodal extension
- cN3b Metastasis in a single or multiple lymph nodes with clinical extranodal extension
Clinical extranodal extension is defined as the presence of skin involvement or soft tissue
invasion with deep fixation to underlying muscle or adjacent anatomical structures or clinical
signs of nerve involvement. Imaging is becoming a standard method of detecting unequivocal
extranodal extension.
Midline nodes are considered ipsilateral nodes.
M – Distant Metastasis
- M0 No distant metastasis
- M1 Distant metastasis
Pathological TNM Classification
The pT categories correspond to the cT categories.
pN – Regional Nodes
- pNX Regional lymph nodes cannot be assessed
- pN0 No regional lymph node metastasis
- pN1 Metastasis in 1–4 lymph nodes without definitive pathologic extranodal extension
- pN1a Metastasis in 1 lymph node without definitive pathological extranodal extension
- pN1b Metastasis in 2–4 lymph nodes without definitive pathological extranodal extension
- pN2 1–4 lymph nodes with definitive pathologic extranodal extension or Metastasis in >4 lymph nodes without definitive pathological extranodal extension
- pN3 Metastasis in >4 lymph nodes with definitive pathological extranodal extension
Pathological extranodal extension (pENE) should only be diagnosed when tumour that is present within the confines of a lymph node definitively transgresses through the entire thickness of the lymph node capsule into the surrounding connective tissue, with or without stromal reaction.
A soft tissue deposit should be considered as at least one lymph node with extranodal extension if it occurs at a site where a regional lymph node would be expected.
The pT categories correspond to the cT categories. Histological examination of a selective neck dissection specimen should ordinarily include six or more lymph nodes. Histological examination of a radical or modified radical neck dissection specimen should ordinarily include 15 or more lymph nodes.
Oropharynx – HPV Independent and Hypopharynx
- pNX Regional lymph nodes cannot be assessed
- pN0 No regional lymph node metastasis
- pN1 Metastasis in a single ipsilateral lymph node, 3 cm or less in greatest dimension without pathological extranodal extension
- pN2 Metastasis described as:
- pN2a Metastasis in a single ipsilateral lymph node, 3 cm or less in greatest dimension with pathological extranodal extension or Metastasis in a single ipsilateral lymph node more than 3 cm but not more than 6 cm in greatest dimension without pathological extranodal extension
- pN2b Metastasis in multiple ipsilateral lymph nodes, none more than 6 cm in greatest dimension, without pathological extranodal extension
- pN2c Metastasis in bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension, without pathological extranodal extension
- pN3a Metastasis in a lymph node more than 6 cm in greatest dimension without extranodal extension
- pN3b Metastasis in a single lymph node more than 3 cm in greatest dimension with pathological extranodal extension or Metastasis in multiple ipsilateral or any contralateral or bilateral node(s) with pathological extranodal extension
Pathological extranodal extension (pENE) should only be diagnosed when tumour that is present within the confines of a lymph node definitively transgresses through the entire thickness of the lymph node capsule into the surrounding connective tissue, with or without stromal reaction.
A soft tissue deposit should be considered as at least one lymph node with extranodal extension if it occurs at a site where a regional lymph node would be expected.
Stage
Oropharynx – HPV Associated
- Clinical
| Stage | T | N | M |
|---|---|---|---|
| Stage I | T0, T1, T2 | N0, N1 | M0 |
| Stage II | T0, T1, T2 | N2 | M0 |
| T3 | N0, N1, N2 | M0 | |
| Stage III | Any T | N3 | M0 |
| T4 | Any N | M0 | |
| Stage IV | Any T | Any N | M1 |
- Pathological
| Stage | T | N | M |
|---|---|---|---|
| Stage I | T0, T1, T2 | N0, N1a, N1b | M0 |
| Stage II | T0, T1, T2 | N2, N3 | M0 |
| T3 | N0, N1a, N1b, N2 | M0 | |
| Stage III | T3 | N3 | M0 |
| T4 | Any N | M0 | |
| Stage IV | Any T | Any N | M1 |
HPV- Independent Oropharynx and Hypopharynx
| Stage | T | N | M |
|---|---|---|---|
| Stage 0 | Tis | N0 | M0 |
| Stage I | T1 | N0 | M0 |
| Stage II | T2 | N0 | M0 |
| Stage III | T3 | N0 | M0 |
| T1, T2, T3 | N1 | M0 | |
| Stage IVA | T1, T2, T3 | N2 | M0 |
| T4a | N0, N1, N2 | M0 | |
| Stage IVB | T4b | Any N | M0 |
| Any T | N3 | M0 | |
| Stage IVC | Any T | Any N | M1 |
Prognostic Factors Grid
Nasopharynx
| Prognostic factors | Tumour related | Host related | Environment related* |
|---|---|---|---|
| Essential | TNM Histological type |
Age Performance status |
Distance from treatment centre Access to specific investigations and/or treatments Socioeconomic status |
| Additional | Plasma EBV-DNA copy number Gross tumour volume Site of metastases SUVmax PD-L1 status |
Co-morbidities | Expertise of a treatment at the specific level (e.g., surgery or radiotherapy) Access to information R status after surgery |
Oropharynx
HPV- associated oropharyngeal carcinoma
| Prognostic factors | Tumour related | Host related | Environment related* |
|---|---|---|---|
| Essential | TNM Surgical resection margin |
Performance status Smoking during radiotherapy |
Distance from treatment centre Access to specific investigations and/or treatments Socioeconomic status |
| Additional | HPV genotype Tumour volume Hypoxia PD-L1 status |
Age, co-morbidities |
Expertise of a treatment at the specific level (e.g., surgery or radiotherapy) Access to information R status after surgery |
HPV- independent oropharyngeal carcinoma
| Prognostic factors | Tumour related | Host related | Environment related* |
|---|---|---|---|
| Essential | TNM Surgical resection margin |
Smoking during radiotherapy | Distance from treatment centre Access to specific investigations and/or treatments Socioeconomic status |
| Additional | Number of involved nodes Tumour volume Hypoxia PD-L1 status |
Age, co-morbidities |
Expertise of a treatment at the specific level (e.g., surgery or radiotherapy) Access to information R status after surgery |
Hypopharynx
| Prognostic factors | Tumour related | Host related | Environment related* |
|---|---|---|---|
| Essential | TNM Surgical resection margin |
Smoking during radiotherapy |
Distance from treatment centre Access to specific investigations and/or treatments Socioeconomic status |
| Additional | Number of involved nodes Tumour volume Hypoxia PD-L1 status |
Age, co-morbidities |
Expertise of a treatment at the specific level (e.g., surgery or radiotherapy) Access to information R status after surgery |
Bone (ICD-O-4C40, 41)
The classification applies to all primary malignant bone tumours except lymphoma, plasmacytoma, plasma cell myeloma/multiple myeloma, surface/juxtacortical osteosarcoma and juxtacortical chondrosarcoma. There should be histological
confirmation of the disease and division of cases by histological type and grade.
The regional lymph nodes are those appropriate to the site of the primary
tumour. Regional node involvement is rare, and cases in which nodal status is
not assessed either clinically or pathologically could be considered N0 instead of
NX or pNX.
TNM Clinical Classification
T – Primary Tumour
- cTX Primary tumour cannot be assessed
- cT0 No evidence of primary tumour
Appendicular Skeleton, Trunk, Skull and Facial Bones
- cT1 Tumour 8 cm or less in greatest dimension
- cT2 Tumour more than 8 cm in greatest dimension
- cT3 Discontinuous tumours in the primary bone site
N – Regional Lymph Nodes
- cNX Regional lymph nodes cannot be assessed
- cN0 No regional lymph node metastasis
- cN1 Regional lymph node metastasis
M – Distant Metastasis
- cM0 No distant metastasis
- cM1 Distant metastasis
- M1a Lung
- M1b Other distant sites
pTNM Pathological Classification
The pT and pN categories correspond to the cT and cN categories, respectively.
Stage – Appendicular Skeleton, Trunk, Skull and Facial Bones
| Stage | T | N | M | Grade |
|---|---|---|---|---|
| Stage IA | T1 | N0 | M0 | G1, GX low grade |
| Stage IB | T2, T3 | N0 | M0 | G1, GX low grade |
| Stage IIA | T1 | N0 | M0 | G2, G3 high grade |
| Stage IIB | T2 | N0 | M0 | G2, G3 high grade |
| Stage III | T3 | N0 | M0 | G2, G3 high grade |
| Stage IVA | Any T | N0 | M1a | Any G |
| Stage IVB | Any T | N1 | Any M | Any G |
| Any T | Any N | M1b | Any G |
Carcinoma of Skin of the Head and Neck Region (ICD-O-4C00.0-2, C00.6, C44.0, C44.2-4)
The classification applies only to cutaneous carcinomas of the head and neck region, excluding the eyelid and excluding Merkel cell carcinoma and melanoma. There should be histological confirmation of the disease.
Anatomical Sites
The following sites are identified by ICD-o-3 topography rubrics:
- Lip including vermillion border and commissure (C00.0-2, C00.6, C44.0).
- External ear (C44.2)
- Other and unspecified parts of face (C44.3)
- Scalp and neck (C44.4).
TNM Clinical Classification
T – Primary Tumour
- cTX Primary tumour cannot be identified
- cT0 No evidence of primary tumour
- cTis Carcinoma in situ
- cT1 Tumour 2 cm or less in greatest dimension
- cT2 Tumour >2 cm and ≤4 cm in greatest dimension
- cT3 Tumour >4 cm in greatest dimension or minor bone erosion or perineural
invasion or deep invasion - cT4a Tumour with gross cortical bone/marrow invasion
- cT4b Tumour with foraminal involvement of the axial skeleton invasion with
foraminal involvement or invasion into the epidural space
Deep invasion is defined as invasion beyond the subcutaneous fat or >6 mm (as measured from the granular layer of adjacent normal epidermis to the base of the tumour). Perineural invasion is defined as tumour cells within the nerve sheath of a nerve lying deeper than the dermis or measuring 0.1 mm or larger in calibre or involvement of five or more nerves per section, without foramen or skull base invasion or transgression.
Axial skeleton includes the skull, vertebrae and sacrum.
N – Regional Lymph Nodes
- cNX Regional lymph nodes cannot be assessed.
- cN0 No regional lymph node metastasis
- cN1 Metastasis in a single ipsilateral lymph node, 3 cm or less in greatest dimension without extranodal extension
- cN2 Metastasis described as:
- cN2a Metastasis in a single ipsilateral lymph node more than 3 cm but not more than 6 cm in greatest dimension without extranodal extension
- cN2b Metastasis in multiple ipsilateral lymph nodes, not more than 6 cm in greatest dimension, without extranodal extension
- cN2c Metastasis in bilateral or contralateral lymph nodes, not more than 6 cm in greatest dimension, without extranodal extension
- cN3a Metastasis in a lymph node more than 6 cm in greatest dimension without extranodal extension
- cN3b Metastasis in a single or multiple lymph nodes with clinical extranodal extension
Clinical extranodal extension is defined as the presence of skin involvement or soft tissue invasion with deep fixation to underlying muscle or adjacent anatomical structures or clinical signs of nerve involvement. Image detected unequivocal extranodal extension is becoming standard.
M – Distant Metastasis
- M0 No distant metastasis
- M1 Distant metastasis
pTNM Pathological Classification
The pT categories correspond to the clinical cT categories.
pN – Regional Lymph Nodes
Histological examination of a selective neck dissection specimen should ordinarily include 10 or more lymph nodes. Histological examination of a radical or modified radical neck dissection specimen should ordinarily include 15 or more lymph nodes.
- pNX Regional lymph nodes cannot be assessed
- pN0 No regional lymph node metastasis
- pN1 Metastasis in a single ipsilateral lymph node, 3 cm or less in greatest dimension without extranodal extension
- pN2 Metastasis described as:
- pN2a Metastasis in a single ipsilateral lymph node, less than 3 cm in greatest dimension with extranodal extension or, more than 3 cm but not more than 6 cm in greatest dimension without extranodal extension
- Metastasis in multiple ipsilateral lymph nodes, not more than 6 cm in greatest dimension, without extranodal extension
- pN2c Metastasis in bilateral or contralateral lymph nodes, not more than 6 cm in greatest dimension, without extranodal extension
- pN3a Metastasis in a lymph node more than 6 cm in greatest dimension without extranodal extension
- pN3b Metastasis in a lymph node more than 3 cm in greatest dimension with extranodal extension or multiple ipsilateral, or any contralateral or bilateral node(s) with extranodal extension
Stage
| Stage | T | N | M |
|---|---|---|---|
| Stage 0 | Tis | N0 | M0 |
| Stage I | T1 | N0 | M0 |
| Stage II | T2 | N0 | M0 |
| Stage III | T3 | N0 | M0 |
| T1, T2, T3 | N1 | M0 | |
| Stage IVA | T1, T2, T3 | N2, N3 | M0 |
| T4 | Any N | M0 | |
| Stage IVB | Any T | Any N | M1 |
Malignant Melanoma of Upper Aerodigestive Tract (ICD-O-4C00-06, C09-14, C30-32)
The classification applies only to mucosal malignant melanomas of the head and neck region, i.e., of the upper aerodigestive tract. There should be histological confirmation of the disease and division of cases by site.
The regional lymph nodes are those appropriate to the site of the primary tumour.
Clinical TNM Classification
T – Primary Tumour
- cTX Primary tumour cannot be assessed
- cT0 No evidence of primary tumour
- cT3 Tumour limited to the epithelium and/or submucosa (mucosal disease)
- cT4a Tumour invades deep soft tissue, cartilage, bone or overlying skin
- cT4b Tumour invades any of the following: brain, dura, skull base, lower cranial nerves (IX, X, XI, XII), masticator space, carotid artery, prevertebral space and mediastinal structures
Mucosal melanomas are aggressive tumours; therefore, T1 and T2 are omitted as are stages I and II.
N – Regional Lymph Nodes
- cNX Regional lymph nodes cannot be assessed
- cN0 No regional lymph node metastasis
- cN1 Regional lymph node metastasis
M – Distant Metastasis
- cM0 No distant metastasis
- cM1 Distant metastasis
Pathological TNM Classification
The pT and pN categories correspond to the cT and cN categories.
- pN0 Histological examination of a regional lymphadenectomy specimen should ordinarily include six or more lymph nodes. If the lymph nodes are negative, but the number ordinarily examined is not met, classify as pN0.
Stage
| Stage | T | N | M |
|---|---|---|---|
| Stage III | T3 | N0 | M0 |
| Stage IVA | T4a | N0 | M0 |
| T3, T4a | N1 | M0 | |
| Stage IVB | T4b | Any N | M0 |
| Stage IVC | Any T | Any N | M1 |
Prognostic Factors Grid – Malignant Melanoma of Upper Aerodigestive Tract
| Prognostic factors | Tumour related | Host related | Environment related* |
|---|---|---|---|
| Essential | TNM Depth of invasion Surgical resection margin |
Co-morbidity Age |
Distance from treatment centre Access to specific investigations and/or treatments Socioeconomic status |
| Additional | Site of primary Tumour Size Tumour mitotic rate Ulceration BRAF mutation status |
Expertise of a treatment at the specific level (e.g., surgery or radiotherapy) Access to information R status after surgery |
Melanoma of Skin (ICD-O-4C00.0-2, C00.6, C21.3, C44, C51, C60, C63.2)
There should be histological confirmation of the disease.
The following are the procedures for assessing N and M categories:
- N categories Physical examination and imaging
- M categories Physical examination and imaging
When patients present with multiple primary melanomas, each different anatomical
site of the skin is considered a different primary.
The classifications applies to melanomas of the skin, including vulva, penis and
perianal skin, but excludes melanomas of the upper aerodigestive tract.
The regional lymph nodes are those appropriate to the site of the primary tumour.
TNM Clinical Classification
T – Primary Tumour
The extent of the tumour is classified after excision, see pT.
N – Regional Lymph Nodes
- cNX Regional lymph nodes cannot be assessed
- cN0 No regional lymph node metastasis
- cN1 Metastasis in one regional lymph node or intralymphatic regional metastasis without nodal metastases
- cN1a Only microscopic metastasis (clinically occult)
- cN1b Macroscopic metastasis (clinically apparent)
- cN1c Satellite or in- transit metastasis without regional nodal metastasis
- cN2 Metastasis in two or three regional lymph nodes or satellite or in- transit metastasis with lymph node metastases
- cN2a Metastasis in two or three regional lymph nodes, with only microscopic nodal metastasis
- cN2b Metastasis in two or three regional lymph nodes, clinically detected in at least one node
- cN2c cN2c Satellite or in- transit metastasis with only one regional nodal metastasis, (microscopic or clinical)
- cN3 Metastasis in four or more regional lymph nodes, or matted metastatic regional lymph nodes, or satellite(s) or in- transit metastasis with metastasis in two or more regional lymph node(s)
- cN3a Metastasis in four or more regional lymph nodes with only microscopic nodal metastasis
- cN3b Metastasis in four or more regional lymph nodes clinically detected in at least one node, or two or more matted nodes.
- cN3c Satellite(s) or in- transit metastasis either with two or more regional nodal metastasis (microscopic or clinical) or two or more matted nodes.
M – Distant Metastasis
- M0 No distant metastasis
- M1 Distant metastasis*
- M1a Skin, subcutaneous tissue or lymph node(s) beyond the regional lymph nodes
- M1b Lung
- M1c Other non- central nervous system sites
- M1d Central nervous system
Suffixes for M category:
(0) lactic dehydrogenase (LDH) – not elevated
(1) LDH – elevated
so that M1a(1) is metastasis in skin, subcutaneous tissue, or lymph node(s) beyond the regional lymph nodes with elevated LDH.
No suffix is used if LDH is not recorded or unspecified.
pTNM Pathological Classification
pT – Primary Tumour
- pTX Primary tumour cannot be assessed
- pT0 No evidence of primary tumour or regressed melanomas
- pTis Melanoma in situ (Clark level I)
pTX includes shave biopsies and curettage that do not fully assess the thickness of the primary.
- pT1 Tumour 1 mm or less in thickness
- pT1a less than 0.8 mm in thickness without ulceration
- oT1b less than 0.8 mm in thickness with ulceration or 0.8 mm or more, but not more than 1 mm in thickness, with or without ulceration
- pT2 Tumour more than 1 mm, but not more than 2 mm in thickness
- pT2a without ulceration
- pT2b with ulceration
- pT3 Tumour more than 2 mm, but not more than 4 mm in thickness
- pT3a without ulceration
- pT3b with ulceration
- pT4 Tumour more than 4 mm in thickness
- pT4a without ulceration
- pT4b with ulceration
Tumour thickness measurements are rounded to the nearest 0.1 mm before the T category is assigned.
pN – Regional Lymph Nodes
The pN categories correspond to the N categories.
- pN0 Histological examination of a regional lymphadenectomy specimen will ordi-
narily include six or more lymph nodes. If the lymph nodes are negative, but
the number ordinarily examined is not met, classify as pN0. Classification
based solely on sentinel node biopsy without subsequent axillary lymph node
dissection is designated (sn) for sentinel nodes, e.g., (p)N1(sn).
Stage
Clinical stage
| Stage | T | N | M |
|---|---|---|---|
| Stage 0 | Tis | N0 | cM0 |
| Stage IA | T1a | N0 | cM0 |
| Stage IB | T1b | N0 | cM0 |
| T2a | N0 | cM0 | |
| Stage IIA | T2b | N0 | cM0 |
| T3a | N0 | cM0 | |
| Stage IIB | T3b | N0 | cM0 |
| T4a | N0 | cM0 | |
| Stage IIC | T4b | N0 | cM0 |
| Stage III | Any T | N1, N2, N3 | cM0 |
| Stage IV | Any T | Any N | cM1 |
Pathological Stage
| Stage | T | N | M |
|---|---|---|---|
| Stage 0 | pTis | c/pN0 | cM0 |
| Stage I | pT1 | c/pN0 | cM0 |
| Stage IA | pT1a | c/pN0 | cM0 |
| pT1b | c/pN0 | cM0 | |
| Stage IB | pT2a | pN0 | cM0 |
| Stage IIA | pT2b | pN0 | cM0 |
| pT3a | pN0 | cM0 | |
| Stage IIB | pT3b | pN0 | cM0 |
| pT4a | pN0 | cM0 | |
| Stage IIC | pT4b | pN0 | cM0 |
| Stage III | Any pT | pN1, pN2, pN3 | cM0 |
| Stage IIIA | pT1a, T1b, T2a | pN1a, pN2a | cM0 |
| Stage IIIB | pT1a, T1b, T2a | pN1b, pN1c, pN2b | cM0 |
| pT2b-T3a | pN1, pN2a, pN2b | cM0 | |
| Stage IIIC | pT1a, T1b, T2a, T2b, T3a | pN2c, pN3 | cM0 |
| pT3b, T4a | N1, N2, N3 | cM0 | |
| pT4b | N1, N2 | cM0 | |
| Stage IIID | pT4b | N3 | cM0 |
| Stage IV | Any pT | Any N | M1 |
If lymph node(s) are identified with no apparent primary, the stage is as follows:
| Stage | T | N | M |
|---|---|---|---|
| Stage IIIB | pT0 | N1b, N1c | M0 |
| Stage IIIC | pT0 | N2b, N2c, N3b, N3c | M0 |
Merkel Cell Carcinoma of Skin (ICD-O-4C00, C44, C51, C60, C63.2, C80)
The classification applies only to Merkel cell carcinomas. There should be histological confirmation of the disease.
The following are the procedures for assessing T, N and M categories:
- T categories Physical examination
- N categories Physical examination and imaging
- M categories Physical examination and imaging
The regional lymph nodes are those appropriate to the site of the primary tumour.
TNM Clinical Classification
T – Primary Tumour
- TX Primary tumour cannot be assessed
- T0 No evidence of primary tumour
- Tis Carcinoma in situ
- T1 Tumour 2 cm or less in greatest dimension
- T2 Tumour more than 2 cm, but not more than 5 cm in greatest dimension
- T3 Tumour more than 5 cm in greatest dimension
- T4 Tumour invades deep extradermal structures, i.e., cartilage, skeletal muscle,
fascia or bone
N – Regional Lymph Nodes
- NX Regional lymph nodes cannot be assessed
- N0 No regional lymph node metastasis
- N1 Regional lymph node metastasis
- N2 In-transit metastasis without lymph node metastasis
- N3 In-transit metastasis with lymph node metastasis
In-transit metastasis: a discontinuous tumour distinct from the primary lesion and located between the primary lesion and the draining regional lymph nodes or distal to the primary lesion.
M – Distant Metastasis
- M0 No distant metastasis
- M1 Distant metastasis
- M1a M1b Lung
- M1c Other site(s)
pTNM Pathological Classification
The pT category corresponds to the T category.
- pN0 Histological examination of a regional lymphadenectomy specimen will ordinarily include six or more lymph nodes. If the lymph nodes are negative, but the number ordinarily examined is not met, classify as pN0.
- pNX Regional lymph nodes cannot be assessed
- pN0 No regional lymph node metastasis
- pN1 Regional lymph node metastasis
- pN1a(sn) Microscopic metastasis detected on sentinel node biopsy
- pN1a Microscopic metastasis detected on node dissection
- pN1b Macroscopic metastasis (clinically apparent)
- pN2 In-transit metastasis without lymph node metastasis
- pN3 In-transit metastasis with lymph node metastasis
In-transit metastasis: a discontinuous tumour distinct from the primary lesion and located between the primary lesion and the draining regional lymph nodes or distal to the primary lesion.
Stage
Clinical stage
| Stage | T | N | M |
|---|---|---|---|
| Stage 0 | Tis | N0 | M0 |
| Stage I | T1 | N0 | M0 |
| Stage IIA | T2, T3 | N0 | M0 |
| Stage IIB | T4 | N0 | M0 |
| Stage III | Any T | N1, N2, N3 | M0 |
| Stage IV | Any T | Any N | M1 |
Pathological stage
| Stage | T | N | M |
|---|---|---|---|
| Stage 0 | Tis | N0 | M0 |
| Stage I | T1 | N0 | M0 |
| Stage IIA | T2, T3 | N0 | M0 |
| Stage IIB | T4 | N0 | M0 |
| Stage IIIA | T0 | N1b | M0 |
| T1, T2, T3, T4 | N1a, N1a(sn) | M0 | |
| Stage IIIB | T1, T2, T3, T4 | N1b, N2, N3 | M0 |
| Stage IV | Any T | Any N | M1 |
Soft Tissues (ICD-O-4 C15-C26, C34-C37, C38.1-3, C47-C49, C51-C53, C58, C60-C68)
The classification only applies to malignant and uncertain behaviour mesenchymal
tumours with metastatic potential (including sarcomas). There should be histological
confirmation of the disease and division of cases by histological type and grade.
Anatomical Sites
- Connective, subcutaneous and other soft tissues (C49); peripheral nerves (C47)
- Retroperitoneum (C48.0)
- Mediastinum: anterior (C38.1); posterior (C38.2); mediastinum, NOS (C38.3).
Histological Types of Tumour
The following histological types are not included:
- Kaposi sarcoma
- Dermatofibrosarcoma (protuberans)
- Fibromatosis (desmoid tumour)
- Sarcoma arising from the dura mater and brain
- Angiosarcoma, an aggressive sarcoma, is excluded because its natural history is not consistent with the classification.
For tumours in paediatric patients, please see page 242.
Malignant phyllodes tumour is staged as a soft tissue sarcoma of the superficial trunk.
The regional lymph nodes are those appropriate to the site of the primary tumour. Regional node involvement is rare, and cases in which nodal status is not assessed either clinically or pathologically could be considered N0 instead of cNX or pNX.
TNM Clinical Classification
T – Primary Tumour
- cTX Primary tumour cannot be assessed
- cT0 No evidence of primary tumour
Head and Neck
- cT1 Tumour 2 cm or less in greatest dimension
- cT2 Tumour more than 2 cm but not more than 4 cm in greatest
- cT3 Tumour more than 4 cm in greatest dimension
- cT4a Tumour invades the orbit, skull base or dura, central compartment viscera, facial skeleton and or pterygoid muscles
- cT4b Tumour invades the brain parenchyma, encases the carotid artery, invades prevertebral muscle or involves the central nervous system by perineural spread
N – Regional Lymph Nodes
- cNX Regional lymph nodes cannot be assessed
- cN0 No regional lymph node metastasis
- cN1 Regional lymph node metastasis
M – Distant Metastasis
- M0 No distant metastasis
- M1 Distant metastasis
pTNM Pathological Classification
The pT and pN categories correspond to the cT and cN categories, respectively.
Stage
There is no stage for soft tissue sarcoma of the head and neck and thoracic and
abdominal viscera.