# Diagnosis and staging of head and neck cancer
# Clinical Presentation
## Otalgia
RED FLAG!!
CN 5, 7, 9, 10
## NPC
Neck mass due to LNP: 90% of all pt's
Hearing loss w/ serous otitis media, tinnitus, nasal obstruction and pain
Unilateral middle ear effusion
CN 2-6 palsy
## Oral Cavity Tumors
Pain, nonhealing mouth ulcers, loosening of teeth, ill-fitting dentures, dysphagia, odynophagia
Cervial LN involvement: 66% of all pt's
## Oropharyngeal Tumors
Dysphagia, odynophagia, otalgia, obstructive sleep apnea, snoring, bleeding, neck mass
* HPV(+) oropharyngeal tumors
* Often present with "cystic" neck mass
* DDx for cystic neck mass: branchial cleft cyst carcinoma (super rare)
* Many don't have other clinical complaints
## Hypopharyneal Tumors
Mostly asymptomatic till late stages
Dysphagia, odynophagia, otalgia, weight loss, hemoptysis, dyspnea, neck mass
## Laryngeal Cancer
Sx dependent on location
Glottic cancers: persistent hoarsness
Supraglottic cancers: discovered lately with airway obstruction and LNP
Primary subglottic cancers: rare. Present with stridor and DOE
## Sinus Tumors
Epistaxis, unilateral nasal obstruction
Late stages: facial and/or head pain (tumor infiltration to nerve and periosteum)
# Pathology
* Squamous cell carcinoma
* 90-95% of all lesions in the oral cavity and larynx
* Well differentiated (greater than 75% of keratinization)
* Moderately differentiated (25-75% keratinization)
* Poorly differentiated (<25% keratinization)
* Verrucous carcinoma (variant of SqCC)
* Adenocarcinoma
* Adenoid cystic carcinoma
* Mucoepidermoid carcinoma
* Leukoplakia: hyperparakeratosis with underlying epithelial hyperplasia. Chance of malignant change: <5%
* Erythroplakia: epithelial dysplasia. Association with CIS or cancer is 40%.
# Staging System
TNM staging system of AJCC (American Joint Committee on Cancer) and UICC (Union for International Cancer Control) 2017
DOI: depth of invasion
ENE: extranodal extension
## Lip and Oral Cavity
|T||
|----|-----|
|TX|primary tumor cannot be assessed|
|Tis|carcinoma in situ|
|T1|size ≦2cm, DOI ≦5mm
|T2|size ≦2cm, DOI >5mm and ≦10mm **OR** size >2cm and ≦4cm, DOI ≦10mm
|T3|size >2cm and ≦4cm, DOI >10mm **OR** size >4cm, DOI ≦10mm
|T4||
|T4a: moderately advanced local disease|size >4cm, DOI >10mm **OR** tumor invades adjacent structures only (eg. through cortical bone of the mandible or maxilla, or involves the maxillary sinus or skin of the face) *Note:* superficial erosion of bone/tooth socket (alone) by a gingival primary is not sufficient for T4 |
|T4b: very advanced local disease|invades masticator space, pterygoid plates, or skull base and/or encases the internal carotid artery|

|N|Clinical|Pathological|
|---|---|---|
|Nx|regional LN cannot be assessed|
|N0|no regional LN mets|
|N1|single ipsilateral LN, ≦3cm
|N2|
|N2a|single ipsilateral LN, >3cm and ≦6cm|single ipsilateral LN, ≦3cm, **ENE(+)** **OR** single ipsilateral LN, >3cm and ≦6cm
|N2b|multiple ipsilateral LN, all ≦6cm
|N2c|bilateral or contralateral LN, all ≦6cm
|N3|
|N3a|LN >6cm
|N3b|LN with **ENE(+)**| **ENE(+)** 但不是pN2a
加註"U"或"L"來表示LN mets在cricoid以上或以下; ENE有無也要加註
cN只要有ENE就算N3b，pN有ENE但單顆且小顆，就只算pN2a

|M||
|---|---|
|M0|no distant mets|
|M1|distant metastasis|

Prognostic staging groups
|T|N|M|staging|
|---|---|---|---|
|Tis|N0|M0|0|
|T1|N0|M0|I|
|T2|N0|M0|II|
|T3|N0|M0|III|
|T1-T3|N1|M0|III|
|T4a|N0-N2|M0|IVA|
|T1-T4a|N2|M0|IVA|
||N3|M0|IVB|
|T4b||M0|IVB
|||M1|IVC|
## Nasopharynx
|T||
|---|---|
|TX|primary tumor cannot be assessed|
|T0|no tumor, EBV-positive cervical LN|
|Tis|carcinoma in situ|
|T1|confined in nasopharynx **OR** extension to oropharynx and/or nasal cavity **WITHOUT** parapharyngeal involvement
|T2|extension to parapharyngeal space **and/or** adjacent soft tissue involvement (medial pterygoid, lateral pterygoid, prevertebral m.)|
|T3|infiltration of bone at skull base, cervical vertebra, pterygoid **and/or** paranasal sinuses
|T4|intracranial extension, involvement of CNs, hypopharynx, orbit, parotid gland **and/or** extensive soft tissue infiltration beyond the lateral surface of the lateral pterygoid m.
[何謂parapharyngeal space請看這](https://hackmd.io/kjmVwal0Sem840kSN78J3Q?both#Parapharyngeal-space)

|N||
|---|---|
|NX|reginal LN cannot be assessed|
|N0|No LN mets|
|N1|unilateral cervical LNs **and/or** unilateral or bilateral mets in retropharyngeal LNs, all ≦6cm, all above the caudal border of cricoid cartilage
|N2|bilateral cervical LNs, all ≦6cm, all above the caudal border of cricoid cartilage
|N3|LN >6cm **and/or** below the caudal border of cricoid cartilage

|M||
|---|---|
|M0|No distant mets|
|M1|Distant mets|
Prognostic staging groups
|T|N|M|staging|
|---|---|---|---|
|Tis|N0|M0|0|
|T1|N0|M0|I|
|T0-T1|N1|M0|II|
|T2|N0-N1|M0|II
|T0-T2|N2|M0|III
|T3|N0-N2|M0|III
|T4|N0-N2|M0|IVA
||N3|M0|IVA
|||M1|IVB
## Oropharynx
|T|p16(-) clinical|p16(-) pathological|p16(+) clinical|p16(+) pathological|
|---|---|---|---|---|
|TX|primary tumor cannot be assessed
|Tis|carcinoma in situ
|T0|X|X|no primary identified
|T1|size ≦2cm
|T2|size >2cm and ≦4cm
|T3|size >4cm **OR** extension to lingual surface of epiglottis
|T4|||invades larynx, extrinsic muscle of tongue, medial pterygoid, hard palate, mandible, or **BEYOND**|
|T4a: moderately advanced local disease|invades larynx, extrinsic muscle of tongue, medial pterygoid m., hard palate, or mandible(註)||X|
|T4b: very advanced local disease|invades lateral pterygoid m., pyterygoid plates, lateral nasopharynx, skull base, or encases carotid artery||X|
p16(-)與p16(+)的差別在於p16(+)不細分T4a和T4b
註：從舌根和會厭谿(vallecula)長出來的腫瘤，如果只入侵會厭lingual side黏膜，並不算laryngeal invasion

|N|p16(-) clinical|p16(-) pathological|p16(+) clinical|p16(+) pathological|
|---|---|---|---|---|
|NX|regional LN cannot be assessed
|N0|no regional LN mets
|N1|single ipsilateral LN, ≦3cm||single or multiple ipsilateral LN, all ≦6cm|≦4LN
|N2|||contralateral or bilateral LN, all ≦6cm|>4LN|
|N2a|single ipsilateral LN, >3cm and ≦6cm|single ipsilateral LN, ≦3cm, **ENE(+)** **OR** single ipsilateral LN, >3cm and ≦6cm|X|X
|N2b|multiple ipsilateral LN, all ≦6cm||X|X
|N2c|bilateral or contralateral LN, all ≦6cm||X|X
|N3|||LN >6cm|X
|N3a|LN >6cm||X|X
|N3b|LN with **ENE(+)**|**ENE(+)** 但不是pN2a|X|X
p16(-)的N算法跟oral cavity的一樣。
p16(+)clinical N只看位置跟大小，不看數量。
p16(+)pathological N只看數量且沒有pN3。

|M|大家都一樣
|---|---|
|M0|no distant mets
|M1|distant mets
Prognostic staging groups
**p16(-) clinical/pathological staging**
|T|N|M|staging|
|---|---|---|---|
|Tis|N0|M0|0
|T1|N0|M0|I
|T2|N0|M0|II
|T3|N0|M0|III
|T1-T3|N1|M0|III
|T4a|N0-N1|M0|IVA
|T1-T4a|N2|M0|IVA
||N3|M0|IVB
|T4b||M0|IVB
|||M1|IVC
**p16(+) clinical staging**
|T|N|M|staging|
|---|---|---|---|
|T0-T2|N0-N1|M0|I
|T0-T2|N2|M0|II
|T3|N0-N2|M0|II
||N3|M0|III
|T4||M0|III
|||M1|IV
**p16(+) pathological staging**
|T|N|M|staging|
|---|---|---|---|
|T0-T2|N0-N1|M0|I
|T0-T2|N2|M0|II
|T3-T4|N0-N1|M0|II
|T3-T4|N2|M0|III
|||M1|IV
## Hypopharynx
|T|clinical/pathological|
|---|---|
|TX|primary tumor cannot be assessed|
|Tis|carcinoma in situ
|T1|limited to one subsite of hypopharynx **and/or** size ≦2cm|
|T2|invades multiple subsite or an adjacent site **OR** size >2cm and ≦4cm **WITHOUT** fixation of hemilarynx
|T3|size >4cm **OR** with fixation of hemilarynx **OR** extension to esophagus
|T4|
|T4a: moderately advanced local disease|invades thyroid/cricoid cartilage, hyoid bone, thyroid gland, or central compartment soft tissue
|T4b: very advanced local disease|invades prevertebral fascia, encases carotid artery, or involves mediastinal structures
[hypopharynx的anatomical subsite請看這](https://hackmd.io/kjmVwal0Sem840kSN78J3Q?both#Hypopharynx)
Central compartment soft tissue包含[strap muscles](https://hackmd.io/kjmVwal0Sem840kSN78J3Q?both#Infrahyoid-strap-muscles)和皮下脂肪
|N|clinical|pathological|
|---|---|---|
|NX|regional LN cannot be assessed
|N0|no regional LN mets
|N1|single ipsilateral LN, ≦3cm|
|N2||
|N2a|single ipsilateral LN, >3cm and ≦6cm|single ipsilateral LN, ≦3cm, **ENE(+)** **OR** single ipsilateral LN, >3cm and ≦6cm|
|N2b|multiple ipsilateral LN, all ≦6cm|
|N2c|bilateral or contralateral LN, all ≦6cm||
|N3|||LN >6cm|
|N3a|LN >6cm||
|N3b|LN with **ENE(+)**|**ENE(+)** 但不是pN2a|

|M||
|---|---|
|M0|no distant metastasis|
|M1|distant metastasis|
Prognostic staging groups
|T|N|M|staging|
|---|---|---|---|
|Tis|N0|M0|0|
|T1|N0|M0|I|
|T2|N0|M0|II|
|T3|N0|M0|III|
|T1-T3|N1|M0|III|
|T4a|N0-N2|M0|IVA|
|T1-T4a|N2|M0|IVA|
||N3|M0|IVB|
|T4b||M0|IVB
|||M1|IVC|
## Larynx
|T|supraglottis|glottis|subglottis|
|---|---|---|---|
|Tx|primary tumor cannot be assessed|
|Tis|carcinoma in situ|
|T1|one subsite, normal vocal cord mobility|limited to vocal cord (may involve ant. post. commissure), normal mobility|limited to subglottis
|T1a|X|limited to one vocal cord|X
|T1b|X|both vocal cords|X
|T2|invades mucosa of more than one subsite of supraglottis or glottis or outside supraglottis (mucosa base of tongue, vallecula, medial wall of pyriform sinus) **WITHOUT** fixation of larynx|extends to supraglottis **and/or** subglottis **and/or** impaired vocal cord mobility|extends to vocal cord **WITH** normal or impaired mobility
|T3|limited to larynx **WITH** vocal cord fixation **and/or** invades postcricoid area, preepiglottic space, paraglottic space, inner cortex of thyroid cartilage|limited to larynx **WITH** vocal cord fixation **and/or** invasion of paraglottic space **and/or** inner cortex of thyroid cartilage|limited to larynx **WITH** vocal cord fixation **and/or** invasion of paraglottic space **and/or** inner cortex of thyroid cartilage
|T4|
|T4a: moderately advanced local disease|invades through the outer cortex of thyroid cartilage **and/or** invades beyond larynx (eg, trachea, soft tissues of neck including deep extrinsic muscle of the tongue, strap muscles, thyroid, or esophagus)|invades through the outer cortex of thyroid cartilage **and/or** invades tissues beyond larynx (eg, trachea, cricoid cartilage, soft tissues of neck including deep extrinsic muscle of the tongue, strap muscles, thyroid, or esophagus)|invades cricoid or thyroid cartilage **and/or** invades tissue beyond larynx (eg, trachea, soft tissues of neck including deep extrinsic muscles of the tongue, strap muscles, thyroid, or esophagus)
|T4b: very advanced local disease|invades prevertebral space, encases carotid artery, invades mediastinum
[Larynx各subsite及其subsite的subsite請看這裡](https://hackmd.io/kjmVwal0Sem840kSN78J3Q?both#Larynx)
|N|clinical|pathological|
|---|---|---|
|NX|regional LN cannot be assessed|
|N0|no regional LN mets|
|N1|single ipsilateral LN, ≦3cm|
|N2|
|N2a|single ipsilateral LN, >3cm and ≦6cm|single ipsilateral LN, ≦3cm, **ENE(+)** **OR** single ipsilateral LN, >3cm and ≦6cm|
|N2b|multiple ipsilateral LN, all ≦6cm|
|N2c|bilateral or contralateral LN, all ≦6cm|
|N3|
|N3a|LN >6cm|
|N3b|LN with **ENE(+)**|**ENE(+)** 但不是pN2a|

|M||
|---|---|
|M0|no distant mets|
|M1|distant mets|
Prognostic staging groups
|T|N|M|staging|
|---|---|---|---|
|Tis|N0|M0|0|
|T1|N0|M0|I|
|T2|N0|M0|II|
|T3|N0|M0|III|
|T1-T3|N1|M0|III|
|T4a|N0-N2|M0|IVA|
|T1-T4a|N2|M0|IVA|
||N3|M0|IVB|
|T4b||M0|IVB|
|||M1|IVC|
## Nasal cavity and paranasla sinuses
|T|maxillary sinus|nasal cavity and ethmoid sinus|
|---|---|---
|TX|primary tumor cannot be assessed
|Tis|carcinoma in situ
|T1|limited to maxillary sinus mucosa **WITHOUT** bone erosion or destruction|restricted to any single subsite, **with or without** bone invasion
|T2|bone erosion or destruction to hard palate or middle ear meatus, except extension to posterior wall(T3) and pterygoid plates(T4a)|invades 2 subsites in a single region **OR** extend to involve an adjacent region withing the nasoethmoidal complex **with or without** bone invasion
|T3|invades bone of posterior wall, subcutaneous tissue, floor or medial wall of orbit, pterygoid fossa, ethmoid sinuses|invades the medial wall of orbit, maxillary sinus, palate, or cribriform plate
|T4|
|T4a: moderately advanced local disease|invades anterior orbital contents, skin of cheek, pterygoid plates, infratemporal fossa, cribriform plate, sphenoid or frontal sinuses|invades anterior orbital contents, skin of nose or cheek, minimal extension to anterior cranial fossa, pterygoid plates, sphenoid or frontal sinuses
|T4b: very advanced local disease|invades orbital apex, dura, brain, middle cranial fossa, cranial nerves other than CN5-2, nasopharynx, or clivus|invades orbital apex, dura, brain, middle cranial fossa, cranial nerves other than CN5-2, nasopharynx, or clivus|
Clivus: sella turcica後面的斜坡
|N|clinical|pathological|
|---|---|---|
|Nx|regional LN cannot be assessed|
|N0|no regional LN mets|
|N1|single ipsilateral LN, ≦3cm|
|N2|
|N2a|single ipsilateral LN, >3cm and ≦6cm|single ipsilateral LN, ≦3cm, **ENE(+)** **OR** single ipsilateral LN, >3cm and ≦6cm|
|N2b|multiple ipsilateral LN, all ≦6cm|
|N2c|bilateral or contralateral LN, all ≦6cm|
|N3|
|N3a|LN >6cm|
|N3b|LN with **ENE(+)**|**ENE(+)** 但不是pN2a|

|M||
|---|---|
|M0|no distant mets|
|M1|distant mets|
Prognostic staging groups
|T|N|M|staging|
|---|---|---|---|
|Tis|N0|M0|0|
|T1|N0|M0|I|
|T2|N0|M0|II|
|T3|N0|M0|III|
|T1-T3|N1|M0|III|
|T4a|N0-N2|M0|IVA|
|T1-T4a|N2|M0|IVA|
||N3|M0|IVB|
|T4b||M0|IVB|
|||M1|IVC|
## Salivary glands
|T|clinical/pathological|
|---|---|
|TX|primary tumor cannot be assessed|
|T0|no evidence of primary tumor
|Tis|carcinoma in situ|
|T1|≦2cm **WITHOUT** extraparenchymal extension
|T2|>2cm and ≦4cm **WITHOUT** extraparenchymal extension
|T3|>4cm **and/or** **WITH** extraparenchymal extension
|T4|
|T4a: moderately advanced local disease|invades skin, mandible, ear canal, facial nerve
|T4b: very advanced local disease|invades skull base, pterygoid plates, encases carotid artery
為了分期，這裡的extraparenchymal單指臨床上或肉眼可見的侵犯，僅有顯微程度侵犯就不算
|N|clinical|pathological|
|---|---|---|
|Nx|regional LN cannot be assessed|
|N0|no regional LN mets|
|N1|single ipsilateral LN, ≦3cm|
|N2|
|N2a|single ipsilateral LN, >3cm and ≦6cm|single ipsilateral LN, ≦3cm, **ENE(+)** **OR** single ipsilateral LN, >3cm and ≦6cm|
|N2b|multiple ipsilateral LN, all ≦6cm|
|N2c|bilateral or contralateral LN, all ≦6cm|
|N3|
|N3a|LN >6cm|
|N3b|LN with **ENE(+)**|**ENE(+)** 但不是pN2a|

|M||
|---|---|
|M0|no distant mets|
|M1|distant mets|

Prognostic staging groups
|T|N|M|staging|
|---|---|---|---|
|Tis|N0|M0|0|
|T1|N0|M0|I|
|T2|N0|M0|II|
|T3|N0|M0|III|
|T1-T3|N1|M0|III|
|T4a|N0-N2|M0|IVA|
|T1-T4a|N2|M0|IVA|
||N3|M0|IVB|
|T4b||M0|IVB|
|||M1|IVC|
## maxillary sinus
|T||
|---|---|
|T1|limited to maxillary sinus; no bone erosion|
|T2|bone erosion or destruction; extending to hard palate and/or middle nasal meatus|
|T3|involve posterior wall, subQ, floor or medial wall of orbit, pterygoid fossa, ethmoid sinus|
|T4||
|T4a|anterior orbital content, skin of cheek, pterygoid plate, infratemporal fossa, cribriform plate, sphenoid or frontal sinus|
|T4b|orbital apex, dura, brain, middle cranial fossa, cranial nerves other then CN5-2, nasopharynx, clivus|

## Nasal cavity and ethmoid sinus
|T||
|---|---|
|T1|restricted to one subsite, with or without bony invasion|
|T2|invading 2 subsites in a single region; involve an adjacent regfion within the nasoethmoidal complex; with or without bony invasion|
|T3|invade the medical wall or floor of orbit, maxillary sinus, palate, or cribriform plate|
|T4||
|T4a|anterior orbital content, skin of nose or cheek, minimal extension to anterior cranial fossa, pterygoid plates, sphenoid or frontal sinus|
|T4b|orbital apex, dura, brain, middle cranial fossa, cranial nerves other then CN5-2, nasopharynx, clivus|