Head and Neck Flashcards
Indications for post op radiation
- Advanced stage disease, pT3 or pT4
- Multiple positive nodes
- Close or positive surgical margins: reresection preferable if possible, concurrent CRT if resection not possible
- Perineural invasion
- Lymphovascular invasion
- Extracapsular extension (gets CRT)
Timing of radiation therapy
Adjuvant: 4-6 weeks after surgery
Primary: 2 weeks after any necessary dental extractions
Complications of radiation therapy
- Mucositis
- Xerostomia
- Dental caries
- Osteoradionecrosis
- Chondroradionecrosis of larynx
- Soft tissue fibrosis
- Dysphagia
- Cranial neuropathy
- Atherosclerosis and long term risk of stroke
- Long term risk of secondary malignancies
Risk factors for ORN after radiation
- Radiation dose > 60 Gy
- Poor oral hygiene or poor dentition
- Location of primary tumor: posterior mandible most commonly affected
- Extent of mandible in radiation field
- Poor nutritional status
- Concurrent chemoradiation
Cisplatin
Most common chemotherapy agent used. Leads to DNA crosslink formation.
- Regimen: high dose q3 weeks protocol (delivered every 3 weeks for 3 weeks) or low dose week protocol (better tolerated)
- Side effects: nephrotoxicity, ototoxicity, alopecia, nausea and vomiting, neutropenia
Carboplatin
Similar mechanism of action as cisplatin (DNA crosslinking). More myelosuppressive, better tolerated than cisplatin. Less ototoxic.
5 Flurouracil
Causes derangements in DNA synthesis and repair. Causes severe mucositis.
- Irreversibly binds to thymidylate synthetase, blocking conversion of uridine to thymidine thereby preventing DNA synthesis
Taxanes
Stabilize microtubules and arrest cells in G2/M phase. In induction chemo addition of taxanes to cisplatin and 5-FU leads to better outcomes than cisplatin and 5-FU alone.
Cetuximab
Monoclonal antibody that binds to epidermal growth factor receptor (which is overexpressed in HNSCC). Improved survival when given concurrently with radiation compared to radiation alone.
When to give chemo concurrently with radiation
When extracapsular extension or positive margins
Radical neck dissection
Resection of levels I-V with sacrifice of internal jugular vein, SCM and spinal accessory nerve
Modified radical neck dissection
Resection of levels I-V with sparing of at least one of the nonlymphatic structures taken in a radical dissection.
Selective neck dissection
- Supraomohyoid: levels I-III
- Lateral neck dissection: levels II-IV
- Posterolateral: levels II-V, suboccipital nodes
- Central neck : level VI
Anatomic landmarks of level Ia
Bounded by anterior bellies of digastric laterally, mandible superiorly, hyoid inferiorly, mylohyoid deep
Anatomic landmarks of level Ib
Bounded anteriorly by anterior belly of digastric, superiorly by body of mandible, posteriorly by posterior belly of digastric
Anatomic landmarks of level II
Upper jugular nodal group extending from skull base superiorly to hyoid inferiorly
IIa - Bordered by posterior belly of digastric superior/anteriorly, anterior to spinal accessory nerve, inferior border is hyoid bone or bifurcation of carotid
IIb- Bordered by spinal accessory nerve anteriorly to posterior border of SCM posteriorly, inferior border level of hyoid bone
Anatomic landmarks of level III
Midjugular nodal group that extends from carotid bifurcation (or hyoid, radiographic landmark) to the junction of the omohyoid and internal jugular vein (or inferior border of cricoid, radiographic landmark)
Anatomic landmarks of level IV
Lower jugular nodal group that extends from junction of omohyoid muscle with internal jugular vein (or inferior border of cricoid) to the clavicle
Anatomic landmarks of level V
Posterior triangular nodes bordered by trapezius posteriorly, and posterior border of SCM anteriorly, inferior border is clavicle
Va- nodes located above a horizontal plane at inferior border of cricoid cartilage
Vb- nodes located below a horizontal plane at inferior border of cricoid cartilage
When to do a neck dissection in the N0 neck
Management (surgery or radiation) indicated when risk of nodal involvement reaches 20% (when depth of invasion > 4mm)
Types of neck dissections that should be done in head and neck cancer when RT is not already planned for T1/T2 N0 cancer
Oral cavity: supraomohyoid (levels I-III), consider bilateral dissection for midline lesions (floor of mouth and tongue)
Oropharynx: Ipsilateral dissection for tonsil primary (at least levels II-IV), bilateral dissection for base of tongue
Supraglottis: bilateral levels II-IV
Hypopharynx: ipsilateral vs bilateral levels II-IV
Type of neck dissection in the T3/T4 N0 neck
- Surgical management of primary should include neck dissection
- Ipsilateral dissection: lateral tongue not crossing midline, retromolar trigone, buccal mucosa, lateral alveolar ridge, tonsil
- Bilateral dissection: oral tongue crossing midline, anterior floor of mouth, soft palate, base of tongue, supraglottis, glottis, hypopharynx
Complications of neck dissections
- Nerve injury: spinal accessory, vagus, hypoglossal, RLN, phrenic, sympathetic chain, brachial plexus, marginal mandibular branch of facial
- Hematoma
- Infection
- Seroma
- Chyle leak
- lymphatic leak
- Skin flap necrosis
- Carotid rupture
Subsites of oral cavity
- Lips
- Buccal mucosa
- Oral tongue
- Floor of mouth
- Hard palate
- Alveolar ridge
- Retromolar trigone
Oral cavity T staging
T1: tumor < 2cm in greatest dimension, and DOI ≤ 5 mm
T2: tumor ≤ 2 cm, DOI > 5 mm and ≤ 10 mm or tumor > 2 cm and ≤ 4 cm and DOI ≤ 10 mm
T3: > 4cm or any tumor with DOI > 10 mm
T4a: Tumor invades adjacent structures only (e.g., through cortical bone of mandible or maxilla, or involves the maxillary sinus or skin of the face; for lip it invades through the cortical bone, inferior alveolar nerve, floor of mouth or skin of face)
T4b: Tumor invades masticator space, pterygoid plates, or skull base and/or encases the internal carotid artery
Oral cavity N staging
Clinical assessment:
NX: Regional lymph nodes cannot be assessed
N0: No regional lymph node metastasis
N1: Metastasis in a single ipsilateral lymph node, ≤ 3 cm and ENE-
N2a: Metastasis in a single ipsilateral lymph node > 3 cm and ≤ 6 cm and ENE
N2b: Metastases in multiple ipsilateral lymph nodes, ≤ 6 cm and ENE-
N2c: Metastases in bilateral or contralateral lymph nodes, ≤ 6 cm and ENE-
N3a: Metastasis in a lymph node > 6 cm and ENE-
N3b: metastasis in any lymph node(s) with ENE+ clinically
Pathologically remainder of above is the same except for -
N2a: Metastasis in a single ipsilateral lymph node, ≤ 3 cm and ENE+; or metastasis in a single ipsilateral lymph node > 3 cm and ≤ 6 cm and ENE-
N3b: Metastasis in a single ipsilateral node larger than 3 cm in greatest dimension and ENE+; or multiple ipsilateral, contralateral, or bilateral nodes, any with ENE+; or a single contralateral node of any size and ENE+
Retromolar trigone
- Mucosal space between third mandibular molar and maxillary tuberosity
- Continuous with buccal mucosa, hard and soft palate, anterior tonsillar pillar, maxillary tuberosity and upper and lower alveolar ridges
Borders: superior - maxillary tuberosity; anterior: posterior aspect of second mandibular molar; lateral - buccal mucosa; medial- anterior tonsillar pillar
Most common site of verrucous carcinoma in head and neck
Buccal
Subsite of the oropharynx
- Palatine tonsils
- Base of tongue (posterior to circumvallate papillae)/ lingual tonsils
- Soft palate and uvula
- Anterior and posterior tonsillar pillars
- Posterior pharyngeal wall
- Vallecula
T Staging for HPV + Oropharynx
T1: Tumor ≤ 2 cm
T2: Tumor > 2 cm and ≤ 4 cm
T3: Tumor > 4 cm or extension to lingual surface of the epiglottis
T4: Moderately advanced local disease; tumor invades larynx, extrinsic muscle of tongue, medial pterygoid, hard palate, or mandible or beyond
N Staging for HPV+ Oropharynx
Clinical-
NX Regional lymph nodes cannot be assessed
N0 No regional lymph node metastasis
N1 One or more ipsilateral lymph nodes ≤ 6 cm
N2 Contralateral or bilateral lymph nodes ≤ 6 cm
N3 Lymph node(s) > 6 cm
Pathologic -
pNX Regional lymph nodes cannot be assessed
pN0 No regional lymph node metastasis
pN1 Metastasis in 4 or fewer lymph nodes
pN2 Metastases in more than 4 lymph nodes
Layers of Vocal fold
squamous epithelium -> superficial lamina propria -> intermediate lamina propria -> deep lamina propria -> vocalis muscle
Sites of larynx
Supraglottis
Glottis
Subglottis
Subsites of supraglottis
Epiglottis
AE folds
Arytenoid cartilages
False vocal folds
Subsites of glottis
True vocal folds
Anterior commissure
Posterior commissure
Ventricle
Laryngeal carcinoma barriers to spread
- Quadrangular membrane (for supraglottis)
- Conus elasticus (for glottis and subglottis)
- Cricothyroid membrane
- Thyrohyoid membrane
- Inner perichondrium
Laryngeal carcinoma pathways to spread
- Broyle’s tendon: vocalis tendon inserted into thyroid cartilage
- Preepiglottic space
- Paraglottic space
T staging for Supraglottis
T1: Tumor limited to one subsite of supraglottis with normal vocal cord mobility
T2: Tumor invades mucosa of more than one adjacent subsite* of supraglottis or glottis or region outside the supraglottis (e.g., mucosa of base of tongue, vallecula, or medial wall of pyriform sinus) without fixation of the larynx
T3: Tumor limited to larynx with vocal cord fixation and/or invades any of the following: postcricoid area, pre-epiglottic tissues, paraglottic space, and/or minor thyroid cartilage erosion (e.g., inner cortex)
T4a: Tumor invades through the thyroid cartilage, and/or invades tissues beyond the larynx (e.g., trachea, soft tissues of the neck including deep extrinsic muscle of the tongue, strap muscles, thyroid, or esophagus)
Note: extrinsic muscles of the tongue are: genioglossus, hyoglossus, styloglossus, and palatoglossus
T4b: Tumor invades prevertebral space, encases carotid artery, or invades mediastinal structures
T staging for Glottis
T1: Tumor limited to the vocal cord(s), which may involve anterior or posterior commissure, with normal mobility
T1a: Tumor limited to one vocal cord
T1b: Tumor involves both vocal cords
T2: Tumor extends to supraglottis and/or subglottis and/or with impaired vocal cord mobility
T3: Tumor limited to the larynx with vocal cord fixation and/or invades paraglottic space, and/or minor thyroid cartilage erosion (e.g., inner cortex)
T4a: Tumor invades through the thyroid cartilage and/or invades tissues beyond the larynx (e.g., trachea, soft tissues of neck, including deep extrinsic muscle of the tongue, strap muscles, thyroid, or esophagus)
Note: extrinsic muscles of the tongue are: genioglossus, hyoglossus, styloglossus, and palatoglossus
T4b: Tumor invades prevertebral space, encases carotid artery, or invades mediastinal structures
T staging for subglottis
T1: Tumor limited to the subglottis
T2: Tumor extends to vocal cord(s) with normal or impaired mobility
T3: Tumor limited to larynx with vocal cord fixation
T4a: Tumor invades cricoid or thyroid cartilage and/or invades tissues beyond the larynx (e.g., trachea, soft tissues of neck, including deep extrinsic muscles of the tongue, strap muscles, thyroid, or esophagus)
Note: extrinsic muscles of the tongue are: genioglossus, hyoglossus, styloglossus, and palatoglossus
T4b: Tumor invades prevertebral space, encases carotid artery, or invades mediastinal structures
Supraglottic laryngectomy
- Can be done for T1, T2 and limited T3 tumors of the supraglottis
- Remove epiglottis, AE folds, false cords, preepiglottic space, portions of hyoid and thyroid cartilage
- Spares the arytenoids and true cords
Supracricoid laryngectomy with criohyoidopexy/cricoepiglottopexy
- Can be done for select T3/T4 glottic and supraglottic cancers
- Must not have arytenoid fixation, cricoid cartilage contact/incision, major preepiglottic space involvement, invasion of thyroid cartilage, perichondrum, hyoid and posterior arytenoid mucosal involvement
- Remove entire thyroid cartilage, bilateral true and false vocal cords, one arytenoid and the paraglottic space
- Spare cricoid, hyoid and at least one arytenoid
Endoscopic cordotomy
- Can be done for T1 glottic cancers located in the mid third
When can laryngofissure and cordectomy be utilized
- Can be done for T1 glottic cancers located in the mid third
Vertical partial laryngectomy
- Done for T1-T2 glottic cancers if the tumor does not extend beyond one third of the opposite cord; < 10mm anterior subglottic extension; <5mm posterior subglottic extension; no posterior commissure, cricoarytenoid joint, AE fold, posterior surface of arytenoids or paraglottic space involvement; FEV1 > 50%
- remove one vocal fold from the arytenoid cartilage to vocal process, false cord, ventricle, paraglottic space and overlying thyroid cartilage
- Vertical height of the larynx is maintained by the retained contralateral thyroid ala
Contraindications for vertical partial laryngectomy
- Fixed TVF
- > 10mm anterior subglottic extension or > 5 mm posterior subglottic extension
- Involvement of posterior commissure
- Bulky transglottic lesions
- Lesions invading thyroid cartilage
- Poor pulmonary function
Contraindications for a supraglottic partial laryngectomy
- Cricoid or thyroid cartilage invasion
- Arytenoid mucosa involvement
- Posterior or anterior commissure involvement
- Impaired TVC motion
- Impaired base of tongue motion
- BOT invasion < 1cm from circumvallate papillae
- Invasion of FOM via vallecular involvement
Contraindications for Supracricoid partial laryngectomy-cricohyoidopexy
- Arytenoid fixation
- > 1.5cm extension anteriorly (cricothyroid membrane) and > 0.5cm posterolaterally
- Cricoid involvement
- Extensive preepiglottic space invasion with bulging beneath the vallecular or extension to the thyrohyoid membrane
- Hyoid bone involvement
- External perichondrial thyroid cartilage involvement or extralaryngeal spread
Contraindications for partial laryngectomy
- Fixed cords
- Cartilage invasion
- Subglottic extension
- Interarytenoid invasion
- Subglottic invasion
- Cervical metastasis (relative contraindication)
Indications for total laryngectomy
- T3/T4 tumors with thyroid cartilage destruction
- Posterior commissure or bilateral arytenoid involvement
- Circumferential submucosal disease
- Subglottic extension with cricoid cartilage involvement
- RT or chemoradiation failures
- Hypopharygneal tumors that spread to the postcricoid mucosa
- Thyroid tumors that invade both sides of the larynx
- Radiation necrosis of the larynx
- Severe irreversible aspiration
Ways to prevent laryngectomy stomal stenosis
- Bevel tracheal cuts
- Minimize tracheal tension
- Cut medial heads of SCM
- Minimize suctioning
- Minimize lary tube use
Complications from total laryngectomy
- Early complications: drain failure, hematoma, infection, pharyngocutaneous fistula, wound dehiscence, hypoglossal nerve injury
- Late complications: stomal stenosis, pharyngoesophageal stenosis or stricture, hypothyroidism
What percentage of patients with prior RT have a pharyngocutaneous fistula after laryngectomy?
30%
Hypopharyngeal SCC is associated with what syndrome?
Plummer Vinson (dysphagia, iron deficiency anemia, hypopharyngeal webs)
- Can see an increased risk in nonsmoking women in their 3rd-5th decades of life
- Most commonly associated with hyopharyngeal cancers in the postcricoid region
Subsites of hypopharynx
- Pyriform sinuses
- Postcricoid space
- Posterior pharyngeal wall
Borders of pyriform sinus
Medial border: AE fold
Lateral border: thyroid cartilage
Superior border: glossoepiglottic fold
Inferior border: cricopharyngeus muscle/ esophageal introitus
Posterior border: lateral pharyngeal wall
Anterior: junction of pyriform sinuses in postcricoid region
Borders of postcricoid space
Superior border: posterior arytenoid cartilages
Inferior border: esophageal introitus
Lateral border: tracheoesophageal groove
Borders of paraglottic space
Anterolateral: thyroid cartilage
Inferiomedial: conus elasticus
Medial: ventricle and quadrangular membrane
Posterior: pyriform sinus
Plummer Vinson syndrome
- Specifically associated with postcricoid SCC
- Primarily affects post menopausal women (85%)
- Dysphagia, iron deficiency anemia, hypopharyngeal/esophageal webs, atrophic gastritis, angular stomatitis
- Chronic irritation from webs progresses to carcinoma
- Syndrome etiology likely the result of nutritional deficiency
Indications for total laryngopharyngectomy
- Cancer involves postcricoid mucosa
- Cancer extends beyond the midline
- Advanced cancer or the posterior hypopharyngeal wall
Nasopharyngeal carcinoma risk factors
- Genetics: 15-20% of nasopharyngeal carcinoma pt have a first degree family member with NPC, HLA-b,c and D haplotypes associated with increased risk
- Environment: high nitrosamine diet of salted fish, eggs and vegetables
- EBV
- Male sex 3:1 ratio
Juvenile nasopharyngeal angiofibroma Chandler staging
Stage I: tumor confined to nasopharynx
Stage II: tumor extends to nasal cavity or sphenoid
Stage III: tumor involves maxillary sinus, ethmoid sinus, infratemporal fossa, orbit, cheek and cavernous sinus
Stage IV: tumor is intracranial
Nasopharyngeal Cancer T staging
T1: Tumor confined to the nasopharynx, or extension to oropharynx and/or nasal cavity without parapharyngeal involvement
T2: Tumor with extension to parapharyngeal space, and/or adjacent soft tissue involvement (medial pterygoid, lateral pterygoid, prevertebral muscles)
T3: Tumor with infiltration of bony structures at skull base, cervical vertebra, pterygoid structures, and/or paranasal sinuses
T4: Tumor with intracranial extension, involvement of cranial nerves, hypopharynx, orbit, parotid gland, and/or extensive soft tissue infiltration beyond the lateral surface of the lateral pterygoid muscle
Nasopharyngeal Cancer N Staging
N1: Unilateral metastasis in cervical lymph node(s) and/or unilateral or bilateral metastasis in retropharyngeal lymph node(s), 6 cm or smaller in greatest dimension, above the caudal border of cricoid cartilage
N2: Bilateral metastasis in cervical lymph node(s), 6 cm or smaller in greatest dimension, above the caudal border of cricoid cartilage
N3: Unilateral or bilateral metastasis in cervical lymph node(s), larger than 6 cm in greatest dimension, and/or extension below the caudal border of cricoid cartilage
Most common site of sinonasal malignancies
- Maxillary sinus (50-70%)
- Nasal cavity (15-30%)
- Ethmoid sinus (10-20%)
Risk factors of sinonasal malignancies
- Wood dust exposure (adenocarcinoma)
- Leather related occupational exposure (adenocarcinoma)
- Smoking (SCC)
- Nickel exposure (SCC)
Kadish system for esthesioneuroblastoma
Kadish A: confined to the nasal cavity
Kadish B: extends to the paranasal sinuses
Kadish C: extends beyond the nasal cavity and paranasal sinuses
Kadish D: lymph node or distant metastasis
Sinonasal carcinoma subsites
- Paranasal sinuses
- Nasal cavity
- Anterior cranial fossa
- Pterygopalatine fossa
- Infratemporal fossa
- Orbital cavity
Most common sinonasal malignancies
Epithelial: SCC, adenocarcinoma, adenoid cystic carcinoma
Nonepithelial: lymphoma, esthesioneuroblastoma, sinonasal undifferentiated carcinoma, mucosal melanoma
Contraindications for endoscopic surgery for sinonasal cancer
- Facial soft tissue extension
- Anteriolateral frontal sinus involvement
- Palate involvement
- Dural involvement beyond midpupillary line
- Mandible involvement
- Orbital extension
Distribution of salivary neoplasms
- 70% in parotid (75% benign)
- 22% in submandibular gland (57% benign)
- 8% minor salivary gland (85% malignant)
Symptoms of deep lobe parotid or parapharyngeal space involvement
Decreased gag reflex (CN IX and X)
Aspiration (CN IX and X)
Asymmetric palate elevation (CN X)
Hoarseness (CNX)
Dysphagia (CNX)
Shoulder weakness (CN XI)
Tongue atrophy/paresis (CN XII)
Ptosis (sympathetic chain)
MRI characteristics in salivary tumors
- Bilateral high T2 signal that does not enhance: more likely Warthin’s tumor
- Unilateral high T2 signal that enhances: more likely pleomorphic adenoma
- Intermediate to low T2 signal: more likely malignant
Mucoepidermoid carcinoma
- Most common salivary gland malignancy (adult and pediatric)
- Can look similar to necrotizing sialometoplasia (hard palate) and adenosquamous carcinoma on FNA
- Grading: low, intermediate, high (higher component of squamous cells to mucus cells)
- Grading correlates to clinical aggressiveness and adjuvant treatment
- MECT1-MAML2 t(11;19) (q21;p13) translocation
Adenoid Cystic Carcinoma
- Second most common salivary malignancy in the parotid gland. Most common malignant tumor of submandibular gland or minor salivary galnd
- Patterns: tubular, cribiform, solid (shows groups of cuboidal cells)
- Slowly progressive, infiltrative growth with distant mets developing over years
- Tendency for perineural invasion
- MYB-NFIB t(6;9) translocation
- Good 5 year, poor 10 year survival
Polymorphous low grade adenocarcinoma
- Arises mainly from minor salivary glands; most commonly from hard/soft palate junction
- Second most common minor salivary gland carcinoma
- Low grade malignancy with excellent prognosis
Acinic cell carcinoma
- Arises mainly in the parotid gland (90% of cases)
- Second most common childhood salivary gland malignancy
- Low grade malignancy but 33% will recur
- 10-15% will develop regional or distant mets
Salivary duct carcinoma
- One of the most aggressive salivary gland cancers
- Generally presents with rapidly growing parotid mass
- Minority present with facial nerve paresis
- High grade by definition (30-40% develop local recurrence, 50-75% develop distant mets)
- Significant minority positive for ERBB2 (Her2/neu) receptors
- Typically negative for estrogen and progesterone receptors
Landmarks to identify facial nerve during parotidectomy
- Tragal pointer (1-1.5cm deep and inferior)
- Tympanomastoid suture line (6-8mm deep)
- Retrograde dissection (marginal mandibular branch at mandible superficial to facial vessels; buccal branch deep to parotidomasseteric fascia, parallel to parotid duct)
- Posterior belly of digastric
Complications of parotidectomy
- Seroma
- Hematoma
- Facial nerve paresis/paralysis
- Frey syndrome
- First bite syndrome
- Salivary fistula
Frey syndrome
Gustatory sweating
- Aberrant cross innervation between postganglionic secretomotor parasympathetic fibers (parotid) to postganglionic sympathetic fibers (sweat glands to the skin)
- Estimated incidence 35-60%
- Diagnosis: minor starch/iodine test
- Treatment: antiperspirant, glycopyrrolate, tympanic neurectomy, botox
First bite syndrome
- Most common after deep lobe parotidectomy with instrumentation in parapharyngeal space
- Characterized by severe cramping or spasm int he parotid with first bite of a meal
- Likely because of loss of sympathetic innervation, causing denervation supersensitivity activated by parasympathetic hyperactivation
- Stimulates exaggerated myoepithelial cell contraction through the parotid
- Treatment: pain meds, acupuncture, botox, time
Desmoplastic melanoma
- Rare overall (<4%) but makes up >50% of desmoplastic melanomas occur in head and neck
- Features: majority are amelanotic, locally aggressive and highly infiltrative, up to 50% with local recurrence, perineural and endoneural infiltration, greater tumor thickness at time of diagnosis
- Pure and mixed variants
Subtypes of melanoma
- Superficial spreading (70%)
- Nodular (15-30%)
- Lentigo maligna
- Desmoplastic (4%)
- Unknown primary (2-8%)
Biopsy of melanoma
- Recommend complete excisional biopsy with 1-2 mm margins
- If can’t do excisional then punch or incisional biopsy through thickest or darkest portion
- FNA, shave biopsy, frozen section not recommended
(prevents evaluation of tumor thickness which dictates treatment)
Melanoma T staging
T1: <1mm thickness
T2: > 1-2mm thickness
T3: > 2-4mm thickness
T4: > 4mm thickness
a - no ulceration
b- ulceration present
Satellite metastasis in melanoma
Defined as a nest of metastatic tumor > .05mm in diameter that is separate from the primary lesion by <2cm
In transit metastasis in melanoma
Defined as a metastatic tumor that is separate from the primary lesion by > 2cm but not in the lymph node basin
Melanoma N staging
N1: one node
N2: 2-3 nodes
N3: Four + notes
a: microscopic (clinically occult)
b: macroscopic (clinically detected)
c: presence of satellite or intransit mets
Indications for SLNB in melanoma
- T2-T4 melanomas
- Some patients with T1b
Histopathologic markers for melanoma
- S100
- Melan-A (MART-1)
- HMB-45
Pathway of right RLN
- Exits vagus nerve at base of neck
- Loops around right subclavian artery
- Returns deep to innominate artery and back to thyroid bed diagonally
- Non-recurrent RLN may rarely occur on right side and enter from lateral course, associated with aberrant retroesophageal subclavian artery
Pathway of left RLN
- Exits vagus nerve at level of aortic arch and ligamentum arteriosum, lateral to the obliterated ductus arteriosus
- Returns to thyroid bed along tracheoesophageal groove at a more medial and vertical course than right RLN
- Crosses deep to inferior thyroid artery 70% of time
Location of parathyroid glands
- Superior parathyroid glands: at the level of the cricoid cartilage, medial/cranial to the intersection of the RLN and inferior thyroid artery
- Inferior parathyroid glands: lateral or posterior surface of lower thyroid pole
Superior glands are deep to the RLN and inferior glands are superficial to the RLN
Thyroid vascular supply
Inferior thyroid artery (branch of the thyrocervical trunk)
Superior thyroid artery (branch of the external carotid artery)
Superior, middle and inferior thyroid veins (drain to the internal jugular or innominate veins)
Genetic alterations in thyroid cancer
Papillary (RET, BRAF, RAS) - BRAF V600E is specific for PTC and found in 70-80% of tall cell variants, RET/PTC arrangements can be seen commonly in pts with history of radiation
Follicular (RAS, PPARG)
Poorly differentiated (RAS, BRAF, TP53)
Anaplastic (TP53, RAS, BRAF, PIK3CA)
Medullary (RET 95% in MEN2)
Thyroid T staging
T1: Tumor ≤ 2 cm in greatest dimension limited to the thyroid
T1a: Tumor ≤ 1 cm in greatest dimension limited to the thyroid
T1b: Tumor > 1 cm but ≤ 2 cm in greatest dimension limited to the thyroid
T2: Tumor > 2 cm but ≤ 4 cm in greatest dimension limited to the thyroid
T3: Tumor > 4 cm limited to the thyroid or gross extrathyroidal extension invading only strap muscles
T3a: Tumor > 4 cm limited to the thyroid
T3b*: Gross extrathyroidal extension invading only strap muscles (sternohyoid, sternothyroid, thyrohyoid or omohyoid muscles) from a tumor of any size
T4: Includes gross extrathyroidal extension into major neck structures
T4a: Gross extrathyroidal extension invading subcutaneous soft tissues, larynx, trachea, esophagus or recurrent laryngeal nerve from a tumor of any size
T4b: Gross extrathyroidal extension invading prevertebral fascia or encasing carotid artery or mediastinal vessels from a tumor of any size
Thyroid N staging
N0: No evidence of regional lymph node metastasis
N0a: One or more cytologic or histologically confirmed benign lymph nodes
N0b: No radiologic or clinical evidence of locoregional lymph node metastasis
N1: Metastasis to regional nodes
N1a: Metastasis to level VI or VII (pretracheal, paratracheal, prelaryngeal / Delphian or upper mediastinal) lymph nodes; this can be unilateral or bilateral disease
N1b*: Metastasis to unilateral, bilateral or contralateral lateral neck lymph nodes (levels I, II, III, IV or V) or retropharyngeal lymph nodes
Thyroid cancer staging
Differentiated thyroid cancer:
Age at diagnosis < 55 years
Stage I: any T any N M0
Stage II: any T any N M1
Anaplastic thyroid cancer: staging automatically starts at IVa
Types of cancer that metastasizes to the thyroid
Kidney, breast, lung, skin (melanoma and SCC)
What % of thyroid FNAs are nondiagnostic or inadequate?
15%
Characteristics of suspicious lymph nodes
- Loss of fatty hilum
- Increased vascularity
- Round nodule configuration
- Solid nodule with hypoechogenicity
- Microcalcifications
PTC Management
- Thyroglobulin level monitoring
- Routine neck ultrasound monitoring
- Elective lateral neck dissection not recommended until N+ disease documented
- Central neck disection recommended for N+ disease, palpable or visualized disease during surgery
Follicular thyroid carcinoma
- Cervical lymphadenopathy less common than PTC
- Classically hematogenous spread
- Distant mets more common than PTC
- FNA cannot distinguish between follicular adenoma and carcinoma
Medullary thyroid cancer
- Arises from parafollicular C cells and secretes calcitonin
- Distant mets present in 50% of patients on presentation
- 30% are familial
- Workup: calcitonin, RET mutation testing (if negative don’t need to test for MEN), serum calcium to test for hyperparathyroidism, 24hr urinary metanephrines and catecholamines and abdominal MRI to assess for pheo
- Surgery: any pheo should be removed first, total thyroidectomy, central neck dissection strongly considered with lateral neck if central +, when primary lesion >1cm ipsilateral lateral neck strongly considered because 60% will have nodal mets
- Surveillence: calcitonin
- RAI no effective
MEN2 syndromes
MEN2A - MTC, pheochromocytoma, hyperparathyroidism
MEN2B: MTC, pheochromocytoma, mucosal neuromas, Marfanoid body habitus
Adjuvant treatment for thyroid cancer
- TSH suppresion: goal TSH of <0.1 for intermediate to high risk patients, goal TSH of 0.1-0.5 for low risk
- RAI: for higher risk PTC and FTC. Indications include any primary tumor >4cm, extrathyroidal extension, distant mets, high risk features. Need TSH elevated > 30ml/L since RAI uptake stimulated by TSH
PTH
- Half life of 3-5 minutes
- Cleared by liver and kidney
- Increase resportion of calcium and decreases resorption of phosphorus
- Converts 25 hydroxyvitamin d3 (calcifediol) to 1,25 OH D3 (calcitriol)
- Stimulates osteoclast activity via osteoblast modulation
- Increases calcium absorption through vitamin D
Calcitonin
- Secreted by parafollicular cells in thyroid gland
- Inhibits bone resoption
Location of superior parathyroid
- Cricothyroid junction approximately 1cm cranial to the juxtaposition of the RLN and inferior thyroid artery
- Paraesophageal location in 1% of cases
- Embyrologically deep to RLN
Location of inferior parathyroid
- Inferior pole of thyroid along the thyrothymic ligament
- Migratory pathway into the anterior superior mediastinum (where up to 33% of missed parathyroid glands are found)
- More variable position compared to superior glands
Arterial supply of parathyroids
- Inferior thyroid artery supply 80% of inferior and posterior glands
- Additional vascularization from plexus of vessels
- Superior thyroid artery may provide dominant arterial supply for superior glands in 10-20% of patients
Key elements of biochemical diagnosis of primary hyperparathyroidism
- High calcium
- Elevated PTH
- Normal creatinine
- Low or low normal phosphate
- Urinary calcium > 125mg/ 24hrs
- Normal 25 OH vitam D and 1,25 OH vitamin D
Symptoms of hypercalcemia
- Nephrolithiasis, urolithiasis (most stones are calcium oxalate)
- Osteitis fibrosis cystica (bone pain, pathologic fractures, cystic bone change), osteoporosis (spares trabecular bone)
- Muscle weakness, fatigue
- Anxiety, psychosis, depression, deafness, dysphagia,
- Peptic ulcer, pancreatitis, cholelithiasis
- Hypertension
Causes of primary hyperparathyroidism
- Parathyroid adenoma
- Parathyroid lipoadenoma
- Parathyroid hyperplasia
- Parathyroid carcinoma
Causes of secondary hyperparathyroidism
- Insufficient calcium intake, decreased calcium absorption, vitamin D deficiency
- Renal insufficiency or failure
Tertiary hyperparathyroidism
Long standing renal insufficiency or failure leading to autonomous parathyroid hyperfunctioning
Hypercalcemia of malignancy
- PTH related protein secretion (lung, esophagus, head and neck, renal cell, ovarian, bladder, pancreatic)
- Ectopic PTH secretion by small cell lung cancer, small cell ovarian cancer, squamous cell lung cancer
- Ectopic 1,25 OH production by B cell lymphoma and Hodgkin disease
- Lytic bone mets (multiple myeloma, lymphoma, breast cancer and sarcoma)
- Tumor cytokines
Familial hypercalcemic hypocalciuria
- Autosomal dominant disorder
- Inactivating mutations in the calcium sensing receptor of the parathyroid gland
- Low 24 hour urine calcium relative to their hypercalcemia
Indications for surgery for asymptomatic primary hyperparathyroidism
- Serum calcium >1mg/dL above the upper limit of normal
- Creatinine clearance reduced > 60ml/min
- Age < 50
- Surgery requested by patient and patient unsuitable for surveillence
Ectopic parathyroid locations
- Mediastinum and thymus
- Retroesophageal
- Intrathyroidal
- Carotid sheath
Medical management of hyperparathyroidism
- Hydration
- Furosemide
- Bisphosphonates
- Estrogen
- Calcitonin
- Calcimimetics (sensitizes PTH receptor to calcium)
5 basic phases of cell cycle
G0: resting state
G1: preparation for cell division; increase in transcription/translation and doubling of macromolecules
S: synthesis phase, replication of chromosomes
G2: continued cellular growth
M: mitosis phase, chromosomes are separated and two daughter cells result
What is the term given to cells in permanent cell cycle arrest
Senescent
What are the key checkpoints within the cell cycle?
G1/S checkpoint: prevent entry into S phase, rate limiting step
Intra S phase checkpoint: halt progression of S phase if damaged DNA is detected
G2/M checkpoint: prevent entry into M phase
M checkpoint: ensure correct replication of DNA and avoid mitotic exit if errors exist
If an error is identified at a cell cycle checkpoint what processes can be activated?
Recruitment of DNA repair effector complexes
Temporary cell cycle arrest, which can lead to senescence or apoptosis depending on the cell and the lesion
What key tumor suppressor protein controls progression through the G1/S checkpoint and the G2/M checkpoint?
p53 (activates p21-> inhibits cyclin and cyclin dependent kinase (CDK) complexes)
What two key classes of molecules regulate a cell’s progress through the cell cycle?
- Cdks: catalytic subunit, require cyclin for activation; result in phosphorylation (activates/inactivates molecules necessary for progression through the cell cycle)
- Cyclines: regulatory subunit that activates Cdk molecules when bound to form a heterodimer
The classic retinoblastoma tumor suppressor protein (pRB) functions to inhibit what key transcription factors, effectively preventing formation of cell cycle related proteins and arresting the cell in G0 phase?
E2F factors
What genes are considered members of the INK4a family of tumor suppressor genes and in what phase of the cell cycle do they inhibit cyclin-CDk complexes?
p16 and p19, G1 phase
The phases G1, S, G2 are collectively referred to as what?
Interphase
Five stages of mitosis
Prophase: condensation of chromatin, polarization of centrosomes and initiation of mitotic spindle formation
Prometaphase: nuclear envelope breaks down, mitotic spindle microtubules attach to chromosomes
Metaphase: alignment of chromosomes at metaphase plate
Anaphase: separation of sister chromatids
Telophase: cytoplasmic division into two daughter cells; chromatid decondensation
What is the estimated average time required for the accumulation of enough genetic alterations to produce traditional head and neck SCC?
20-25 years
Field cancerization
Term used to describe histopathologic changes seen in mucosa surrounding invasive carcinoma and result in an increased incidence of second primary tumors. Thought to be due to abnormal and genetically unique clones that form independently at multiple sites due to exposure to similar environmental changes or due to a single tumoral clone that forms and subsequently migraes via lateral movement through the mucosa.
Why might alcohol function as a synergistic carcinogen with other environmental carcinogens?
It may decrease the effectiveness of both local and systemic detoxification enzymes (cytochrome P450)
Describe the cell cycle dysregulation that is commonly seen in patients with environmentally related head and neck cancer.
- Loss of p16 (normally inhibits cyclin D)
- upregulation of cyclin D
- loss of p53 (normally inhibits cell cycle progression and promotes apoptosis)
- upregulation of EGFR (enhances mitogenic signaling)
- upregulation of COX-2 (increased angiogenesis, decreased apoptosis)
- increased chromosomal instability (increased aneuploidy)
What genetic conditions are related to an increased risk of head and neck cancer?
- Fanconi anemia (autosomal recessive, DNA repair gene mutation)
- Cowden syndrome (autosomal dominant, TPEN hematoma tumor syndrome; PTEN is a tumor suppressor gene)
- Mutations in cyp P450 enzymes
The HPV DNA encodes 9 open reading frames (genes) on a single strand of its double stranded circular DNA. 7 are considered early phase genes (E) and two are considered late phage genes (L). What are the general functions of E and L genes?
E: regulate transcription of viral DNA
L: encode capsid proteins involved in viral spread
Name the two viral onco-proteins in HPV related tumorigenesis and identify the two genes that control the transcription of these viral proteins?
- E6/E7: onco genes
- E1/E2: transcriptional regulators
When HPV DNA integrates into host DNA the process can result in deletion or loss of function of the E1 and E2 viral genes. This in turn results in what?
Loss of regulation of E6 and E7 and subsequent transcription of these viral genes
What HPV protein functions to inhibt the function of p53 by targeting it for ubiquitin dependent degradation and what is the result?
E6. Results in progressiong though G1 checkpoint and inhibition of apoptosis.
What HPV protein phosphorylates pRb and thus targest it for ubiquitin dependent degradation? What is the primary result?
E7. Results in releast of pRb inhibition of E2F, activation of cell cycle related transcription and progression through the G1 checkpoint.
In addition to E2F related transcription, the degradation of p53 results in over expression of what important protein and what impact does this have on the cell cycle progression?
p16. Normally inhibitics Cdk4/6, but with the loss of p53, pRb, does not meaningfully result in cell cycle control. Can be used as a biomarker of HPV activity.
In addition to HPV what viruses have been associated with head and neck cancer?
- EBV (nasopharyngeal carcinoma)
- HIV (increased risk of all head and neck cancers)
- merkel cell polyomavirus (merkel cell carcinoma)
- Human T lymphotrophic virus (HTLV-1, human T cell lymphoma/leukemia)
- Kaposi sarcoma associated herpesvirus (Kaposi sarcoma)
EGFR is a transmembrane glycoprotein that when activated by binding an extracellular ligand results in dimerization, tyrosine kinase activation and a complex downstream pathway that ultimately results in what major outcomes?
- Cellular growth and proliferation
- Apoptosis
- Angiogenesis
- Invasion
- Metastasis
How does EGFR expression relate to prognosis in head and neck cancer
Increased expression and amplification are related to decreased recurrence free survival and cancer specific survival rates.
What strategies have been used to target aberrant signaling in head and neck SCC based on better understanding of EGFR signaling?
- Tyrosine kinase inhibitors (geftinib)
- Monoclonal antibodies inhibiting dimerization (cetuximab)
- Antisense oligodeoxynucleotide or small interfering mRNA inhibition of mRNA expression
What inflammatory mediator is elevated in head and neck cancer cells
Prostaglandins as a result of the upregulation of COX-1 and 2
What nerves might be implicated in referred otalgia?
CN V3, IX (via Jacobsons nerve), X (via Arnold nerve), and VII as well as branches of C2 and C3 through the great auricular nerve.
What premalignant lesion can present as a thickened white patch that can’t be scarped off on physical exam of mucosa that can progress to invasive carcinoma in up to 30% of patients?
Leukoplakia
What premalignant lesion can appear as a flat red patch with a malignant potential of up to 60% over a variable number of years?
Erythroplakia
What are frequently used as radiographic criteria for a nodal malignancy on CT scan?
- Size > 1cm
- Evidence of central necrosis (~100% specificity)
- Spherical shape (suggestive)
- Nodal grouping in the predicted drainage pathway, with nodes > 1cm
In what situations is evaluation with MRI most useful during the workup for head and neck cancer?
- Soft tissue tumor
- Intracranial extension or skull base involvement
- Paranasal sinus disease
- Nasopharyngeal tumors
- Temporal bone
- Assessment of perineural invasion
What head and neck tumors have either variable/inconsistent or no FDG avidity?
- Well differentiated thyroid cancer
- Medullary thyroid cancer
- Indolent lymphomas
- Neuroendocrine tumors
- Teratomas
- Soft tissue sarcomas
What might result in a false positive result on a PET/CT?
- Infection
- Normal physiologic activity (brain, kidneys)
- Inflammation (after radiation, surgical resection, aspiration/biopsy)
- Osteoradionecrosis
- Granulomatous disease
- Patient movement
What is one of the major limitations of PET/CT which can result in a false negative?
It is unreliable for lesions <1cm in diameter
Which immunohistochemical marker is associated with carcinomas and papillomas?
Cytokeratin
Which immunohistochemical marker is most commonly associated with neural/cartilaginous tumors, melanoma and Langerhans cell histiocytosis?
S-100
Which immunohistochemical marker is associated with neuroendocrine tumors?
- Neuron specific enolase (NSE)
- Chromogranin
- Synaptophysin
Which immunohistochemical marker is most commonly associated with lymphoma?
- Leukocyte common antigen (LCA/CD45)
- CD 20 -> B cell specificity
- CD2 -> T cell specificity
Which tumors stain positive for vimentin and for desmin?
Vimentin -> sarcomas, lipomas, myomas
Desmin -> sarcomas, myomas
What sybtype of SCC is commonly seen in HPV+ oropharyngeal tumors and are more likely to present at an advanced stage owing to early nodal and distant metastasis?
- Basaloid carcinoma
- Despite early regional mets, these tumors are failry sensitive to tx and therefore have better prognosis than conventional SCC
Histopathology for spindle cell carcinoma
Also called carcinosarcoma or pseudosarcoma because it includes a squamous cell lesion on the surface and a more notable underlying malignant spindle cell component. Currently it is thought it arises from epithelial cells and undergoes mesenchymal differentiation
Why are spindle cell carcinomas also known as sarcomatoid, carcinosarcoma or pseudosarcoma?
- Contains a superficial squamous cell lesion and a deeper malignant spindle cell component
- Stain positive for both cytokeratin (epithelial cells) and vimentin (mesenchymal cells)
- Arises from epithelial cells and then undergoes mesenchymal differentiation
How can adenosquamous carcinoma be distinguished from mucoepidermoid carcinoma?
Mucoep doesn’t include a mucosal component. Adenosquamous carcinoma has a predominant mucosal squamous cell component and a deeper adenocarcinoma component.
What squamous cell subtype manifests as slow growing, velvety, exophytic, warty mass in elderly patients and what pathologic feature determines prognosis?
- Verrucous carcinoma
- Focal areas of high grade SCC
Most common sites of metastasis for head and neck SCC
- lungs (66%)
- bone (22%)
- liver (10%)
- less often skin, mediastinum and bone marrow
Traditionally, what single prognostic factor has been shown to decrease overall survival by as much as 50%?
Regional nodal disease
When considering nodal disease what factors have been considered negative prognostic features?
- Presence of nodal disease
- Increasing nodal size
- Extracapsular spread
- Bilateral neck disease
- Matted lymph nodes
- Disease in levels IV and V
- “Skipped” levels
- Invasion of local structures by nodal disease
- Confluence of primary disease and nodal disease
- Total number of involved lymph nodes
What tumor markers can be used to help determine prognosis in head and neck cancer?
- EGFR amplification and overexpression
- HPV status
- Loss of heterozygosity (suggests loss of tumor suppressor gene function)
- Aneuploidy
Neoadjuvant/induction therapy
Treatment approaches uses chemotherapy and or radiation therapy before definitive therapy
Concurrent therapy
Aka concomitant therapy, uses chemo and radiation together as primary treatment modality
Adjuvant therapy
Treatment apporahc that uses radiation therapy with or without chemoptheray after primary surgical management
Describe the three phases of clinical trials
- Phase I: defines maximum tolerated dose or safety of a drug or invasive medical device
- Phase II: includes more patients than phase I; assess the efficacy and side effects or toxicity associated with the intervention of interest
- Phase III: randomized prospective trial comparing the intervention of interest with standard of care
What % of patients with locally advanced head and neck SCC die from recurrent locoregional disease within 5 years of initial treatment?
30-50%
Median length of survival for a patient diagnosed with locally advanced or metastatic head and neck SCC?
6-9 months
General surveillance schedule for exam and imaging for head and neck cancer patients?
Year 1: see every 1-3 months
Year 2: see every 2-4 months
year 3-5: see every 4-6 months
> 5 years: see 6-12 months
Imaging: within 6 months of treatment end for T3-4 or N2-3 cancers of oropharynx, hypopharynx, glottic/supraglottic larynx and nasopharynx. Additional imaging based on concerning signs and symptoms
When should you check a patient’s TSH level after completion of tx for head and neck cancer?
If the neck was irradiated check every 6-12 months
What 3 major categories should be considered when determining candidacy for surgical intervention for head and neck cancer patients?
Physiologic: cardiorespiratory fitness, coag status, immune status, weight loss
Anatomical: surgical acess to subsite of interest
Oncologic: ability to achieve surgical margins, acceptable morbidity with complete resection
Why is it clinically important from both a prognostic and management standpoing to identify the site of origin for an unknown primary tumor?
Failure to identify origin results in significant decrease 5 year overall survival and results in the need for wide field radiation therapy with increase in associated morbidity
At what point during the cell cycle are cells most radiosensitive and radioresistant?
Radiosensitive: M phase and G2
Radioresistant: S phase
How does radiation result in cell killing?
Radiation therapy produces intracellular ionization -> breaks chemical bonds, creates free radicals -> DNA damage -> cell death. Double strand breaks are the most important and deadly injury imposed by radiation
Althogh radiation can result in rapid cell death some cells don’t diet until they attempt mitosis and others continue to divide several times before celld eath. What is this delayed cell killing called?
Mitotic cell death. This is why tumors do not shrink immediately after radiation and may take weeks to demonstrate the full effects of radiation treatment.
Common acute (days to week) toxicities associated with radiation to head and neck?
- Mucositis
- Dermatitis
- Xerostomia
- Hoarseness
- Odynophagia
- Dysphagia
- Weight loss
Common delated (months to years) toxicities associated with radiation treatment
- Xerostomia
- Dental caries/decay
- Osteoradionecrosis, chondronecrosis
- Fibrosis
- Hypothyroidism
- Neurologic damage
What class of chemotherapeutic agents target DNA and cause cross linking, double strand breaks, or substitutions, therby interfering with DNA replication and ultimately causing mutation and or cell death?
Alkylating agents
What inorganic platinum chemotherapeutic agent results in DNA cross links, denaturation of strands, covalend bonds with DNA bases and DNA intrastrand cross links?
Cisplatin
What common side effects are associated with cisplatin administration?
Nephrotoxicity, ototoxicity, neurotoxicity, nausea/vomting, electrolyte disturbances, myelotoxicity
Second generation platinum agent that binds with DNA to create intrastrand and intrastrand cross links and protein DNA cross links that ultimately result in interruption of the cell cycle and apoptosis
Carboplatin
Methotrexate
Binds to dihydrofolate reductase which is necessary for de novo synthesis of thymidine and purine synthesis
Cultured Streptomyces spp produce compounds that function as antibiotic chemotherapeutic agents. Name three of these antitumor antibiotics and their mechanism of action
-Doxorubicin - results in intercalation between base pairs
- Bleomycin: form complexes with iron, thus reducing oxygen to superoxide and hydroxyl radicals which result in DNA strand breaks
- Mitomycin: results in DNA cross linking, alkylation and oxygen radiacals
What class of chemo agents bind to free tubulin dimers and result in disruption of microtubule polymerization or depolymerization and ultimate disruption of the cell cycle
Alkaloids
- VincristingL binds irreversibly to microtubules and spindle proteins in S phase and interferes with the mitotic spindle -> arrest in metaphase
- Vinblastine: binds to tubulin and inhibits microtubule formation, disrupts mitotic spindle -> arrest in M phase
Class of chemo agents that cause stabilization of microtubules inhibiting normal cell cycle by preventing microtubule disassembly and arrest in G2/M phase?
Taxanes
- Docetaxel
- Paclitaxel
What recombinant humanized monoclonal antibody targets EGFR and is currently being investigated in head and neck cancer?
Bevacizumab
What are some of the attributes that definie high risk disease in head and neck cancer patients that benefits from adjuvant chemotherapy?
- Positive surgical margins
- Extracapsular extension
- T3/T4 primary
- Higher nodal stage
- Perineural invasion
- Angiolymphatic invasion
- Involvement of level IV or V lymph nodes
How is level IB distinguished from level IIA surgically and radiographically?
Posterior edge of the submandibular gland
How is the lateral border of level IIA defined radiographically
Posterior border of the internal jugular vein
What anatomical structure divides lymph node level II into IIA and IIB surgically
Spinal accessory nerve (CN XI)
How are the superior and inferior boundaries of level IIA surgically definited?
Superior: skull base
Inferior: carotid bifurcation
What are the radiographic and surgical landmarks that separate neck levels II and III?
Radiographic: inferior border of the hyoid bone Surgical: carotid bifurcation
What are the superior and inferior borders of level III radiographically
Superior: inferior border of hyoid
Inferior: inferior border of cricoid
What are radiographic and surgical landmarks that separate level III and IV
Radiographic: inferior border of cricoid cartilage
Surgical: omohyoid muscle
What anatomic structure divides lymph node level V into Va and Vb
A horizontal plane from the inferior border of the cricoid cartilage
Level VA includes spinal accessory nodes, VB includes transverse cervical nodes and supraclavicular nodes. Just inferior to the clavicle lies the sentinel node or Verchow node
What are the surgical landmarks that define level VI
Hyoid bone superiorly, suprasternal notch inferiorly, common carotid arteries laterally
Level VI nodes are at greatest risk for metastasis from which primary locations?
- Glottic and subglottic
- Pyriform sinus
- Cervical esophagus
- Thyroid gland
What are the major divisions of cervical fascia in the neck?
Superficial cervical fascia
Deep cervical fascia: superficial (investing), middle (visceral) and deep layers
What layer of cervical fascia covers the superficial surface of the platysma and is continuous with the SMAS superiorly?
Superficial cervical fascia
Which layer of cervical fascia arises from the vertebral spinous processes, wraps around the SCM and trapezius muscles, covers the mylohyoid muscle and anterior bellies of the digastric, attaches to the hyoid bone and forms the floor of the submandibular and posterior triangle?
Superficial layer of the deep cervical fascia
What are the two subdivisions of the middle layer of the deep cervical fascia?
Muscular division: surrounds infrahyoid strap muscles, attached superiorly to the hyoid bone and thyroid cartilage and inferiorly to the sternum
Visceral division: surrounds the thyroid, trachea and esophagus and extends into the mediastinum to connect with the fibrous pericardium. Superiorly, the fascia may blend with the buccopharyngeal fascia (controversial)
Name the fascial layers that line the inner (pharyngeal) and outer (cervical) surface of the pharyngeal constrictor muscles.
Inner: pharyngobasilar fascia
Outer: buccopharyngeal fascia
What are the two names divisions of the deep layer of the deep cervical fascia?
Prevertebral fascia: fuse to the transverse processes of the vertebral bodies with extension medially to cover the prevertebral musculature and vertebral bodies. Continues posteriorly to cover the extensor muscles and insert onto the vertebral spinous processes.
Alar fascia: located between the prevertebral fascia and the visceral division of the middle layer of the deep cervical fascia
What layers of the cervical fascia from the carotid sheath?
The superficial (investing), middle (visceral) and deep layers of the deep cervical fascia
What is enveloped by the superficial (investing) layer of the deep cervical fascia?
- Two muscles (SCM and trapezius)
- Two glands (parotid and submandibular gland)
- Two spaces (posterior triangle, suprasternal space of Burns)
What is the vascular supply and innervation of the platysma muscle
Innervation: cervical branch of the facial nerve (VII)
Arterial supply: submental branch of the facial artery and suprascapular artery
What is the innervation and blood supply of the SCM
Innervation: spinal accessory nerve (CN XI), ventral rami of C2-4
Arterial supply: occipital and posterior auricular arteries, superior thyroid artery, suprascapular artery
Innervation and arterial supply of anterior and posterior bellies of digastric
Innervation: anterior belly -> mylohyoid branch of inferior alveolar nerve (V3); posterior belly -> facial nerve
Arterial supply: anterior belly -> submental branch of facial artery; posterior belly -> posterior auricular and occipital arteries
What is the predominant innervation and vascular supply to the infrahyoid straps
Innervation: ansa cervicalis (C1-3)
Arterial supply: superior thyroid artery and lingual artery
What muscle can be found in the lateral neck extending from the transverse processes of C3-C6 to the first rib, passing just posterior to the phrenic nerve, just anterior to the subclavian artery, and just medial to the brachial plexus?
Anterior scalene muscle
What spinal nerve provide sensory innervation to the cervical skin?
Ventral rami of C2-4
-Lesser occipital nerve (C2): posterior scalp and ear
-Greater auricular nerve (C2,C3): anterior branch -> skin over parotid gland; posterior branch -> mastoid area, lower ear and lobule
-Transverse cutaneous nerve (C2, C3): Ascending/descending branches ->anterolateral neck skin
-Supraclavicular nerve (C3, C4): Medial, intermediate and lateral (posterior) branches -> supraclavicular skin from second rib to shoulder
What anatomical location describes the point where the cutaneous nerves of the cervical plexus exit posterior to the SCM and what is the relationship between this point and the spinal accessory nerve (CN XI)?
Erb’s point
- The spinal accessory nerve (CN XI) passes approximately 1cm superior and deep to the SCM muscle and Erb’s point.
What are the muscular branches that constitute the cervical plexus?
- Phrenic nerve (C3-C5)
- Inferior branch of ansa cervicalis (C1-3)
- Segmental branches including cervical branches of the spinal accessory nerve (C1-4)
What structure travels deep to the deep cervical fascia and superficial to the anterior scalene and can be found when dissecting levels III and IV?
Phrenic nerve
The submandibular duct passes between what two nerves
Hypoglossal and lingual nerves
The sympathetic trunk travels deep and medial to the carotid sheath and is just superficial to the prevertebral fascia and what muscle?
Longus colli
Pathway of right recurrent laryngeal nerve
Branches off vagus at approximately T1-2, wraps around the subclavian artery from anterior to posterior, ascends in the neck along the tracheoesophageal groove, generally posterior to the inferior thyroid artery, and enters the larynx at a 30-45 degree angle by passing under the inferior constrictor muscle and through the cricothyroid joint space
Pathway of left recurrent laryngeal nerve
Wraps around the aortic arch before passing superiorly in the neck in the tracheoesophageal groove to enter the larynx at 0-30 degree angle by passing under the inferior constrictor muscle and through the cricothyroid
Describe the classic relationship between the inferior thyroid artery and the recurrent laryngeal nerve
50%: nerve passes deep to artery
25%: nerve passes between arterial branches
25%: nerve passes anterior to artery
This relationship is extremely variable and may not represent a reliable landmark for identifying the nerve
What is the incidence of right nonrecurrent inferior/recurrent laryngeal nerve?
.05-1%
What anomaly is associated with a right aberrant retroesophageal subclavian artery? Situs inversus?
- Right nonrecurrent inferior/recurrent laryngeal nerve
- Left nonrecurrent inferior/ recurrent laryngeal nerve
What structure is formed by the anastamoses of the posterior (dorsal) recurrent laryngeal nerve fibers and the posterior (dorsal) fibers of the infernal branch of the SLN?
Galen anastamosis (aka ramus anastomaticus)
What artery branches from the aortic arch, passes over the trachea from left to right and branches into the right common carotid artery and right subclavian artery?
Innominate (brachiocephalic) artery
What artery branches off the first part of the subclavian artery, ascends in the neck by passing through the foramina of the transverse processes of C1-C6 and enters the foramen magnum and joins with its paired contralateral vessel to form the basilar artery?
Vertebral artery
What are the three arteries that arise from the first part of the subclavian artery?
- Vertebral artery
- Thyrocervical trunk
- Inferior thoracic artery
Name the branches of the thyrocervical trunk that branch off the first part of the subclavian artery at approximately the medial border of the anterior scalene muscle?
- Inferior thyroid artery
- Suprascapular artery
- Superficial/transverse cervical artery
What vessels come off the costocervical trunk?
- Deep cervical artery
- Superior intercostal artery
At what vertebral level is the carotid bifurcation in the majority of people?
C3-C4 (at the level of the superior border of the thyroid cartilage)
What bony skull base structure runs between the internal and external carotid arteries?
Styloid process
What are the branches of the external carotid artery?
- Superior thyroid
- Ascending pharyngeal
- Lingual
- Facial
- Occipital
- Posterior auricular
- Internal maxillary artery
- Superficial temporal
Named branches of superior thyroid artery
Infrahyoid, superior laryngeal, cricothryoid and SCM arteries
Named branches of ascending pharyngeal artery
Pharyngeal, inferior tympanic, meningeal arteries
Named branches of lingual artery
suprahyoid, dorsal lingual, sublingual arteries
Named branches of facial artery
Ascending palatine, tonsillar, submental, labial arteries
Named branches of occipital artery
upper and lower branches to the SCM
Named branches of posterior auricular artery
Stylomastoid artery
Named branches of superficial temporal artery
Frontal and parietal branch
Course of the facial artery
Arises at the level of the greater cornu of the hyoid bone from the external carotid, runs deep to the posterior belly of the digastric muscle and stylohyoid muscle, turns at the middle constrictor to follow the posterior boundary of the submandibular gland and medial border of the medial pterygoid muscle and then winds around the mandible at the level of the facial notch
What artery often transverses level IIB in the neck and “tethers” the hypoglossal nerve in level IIA
Occipital artery
What are the three parts of the internal maxillary artery?
- First part: mandibular portion - arises between the ramus of the mandible and sphenomandibular ligament, passes posterior to the lateral pterygoid muscle
- Second part: pterygoid portion - within the lateral pterygoid muscle
- Third part: pterygopalatine portion - peterygopalatine fossa
What are the branches of the mandibular portion of the imax artery?
- deep auricular
- anterior tympanic
- middle meningeal
- accessory meningeal
- inferior alveolar
- mylohyoid artery
What are the branches of the pterygoid portion of the imax artery?
- anterior deep temporal artery
- posterior deep temporal
- pterygoid branches
- masseteric artery
- buccinator/buccal artery
What are the branches of the pterygopalatine portion of the imax atery?
- posterior superior alveolar artery
- infraorbital artery
- sphenopalatine artery
- artery of the ptergoid canal
- pharyngeal artery
What sensory organ is located at the bifurcation of the common carotid artery and what is the innervation?
- Carotid sinus -> internal carotid artery, baroreceptor, glossopharyngeal, vagus and sympathetics
- Carotid body -> posterior or between carotid bifurcation, chemoreceptor, same innervation as carotid sinus
What vein gives rise to external jugular vein, what structures does it drain and where does it drain into?
- Retromandibular vein and postauricular vein
- Drains scalp and face
- Drains into subclavian vein
What superficial veins drain the anterior neck by emptying into the external jugular vein or the subclavian vein and are at risk during thyroidectomies and tracheostomy?
Anterior jugular veins
What structures exit the skull base through the jugular foramen with the internal jugular vein?
Cranial nerves IX, X and XI, inferior petrosal sinus
The internal jugular vein drains most of the head and neck into what venous structure
Subclavian vein -> brachiocephalic vein
What structure commonly passes from the superior mediastinum, though the thoracic inlet on the left into level IV, passing anterior to the phrenic nerve and anterior scalene muscle, posterior to the carotid sheath, and most commonly terminates at the confluence of the left subclavian vein and internal jugular vein?
Thoracic duct
What is the incidence of right sided thoracic duct in the neck? Bilateral?
Right sided only - 4%
Bilateral - 12-15%
What % of neck masses in pediatric patients are benign?
> 90%, most common inflammatory
What % of neck masses i adult patients are neoplastic?
80%
What is the most common head and neck malignancy in the pediatric population and the second most common head and neck malignancy in the adult population after squamous cell carcinoma
Lymphoma
What are the common sites of origin for locoregional metastatic disease to cervical lymph nodes?
- Upper aerodigestive tract
- Head and neck skin
- Major and minor salivary glands
- Thyroid gland
What are the most common sites of origin for distant metastatic disease to cervical lymph nodes?
- Lung
- Thoracic esophagus
- Ovary
- Prostate
- Kidney
What is the most likely site of origin for SCC metastatic to cervical lymph nodes with an unknown primary?
Oropharynx (tonsil and tongue base)
Most common symptoms associated with nodal metastases to the neck?
- Palpable neck mass
- Symptoms resulting from compression (dysphagia, dysphonia)
- Symptoms resulting from invasion (RLN paralysis, accessory neuropathy, pain)
What is the most common anterior neck mass diagnosed on physical exam?
Thyroid nodule
What is the best diagnostic test for determining the cause of a neck mass without a known primary tumor?
FNA
What diagnostic test is indicated if an FNA biopsy is performed on a suspicious cervical lymph node with an unknown primary and the pathology demonstrates lymphoid cells?
Excisional lymph node biopsy, commonly in the OR
For a patient with SCC of the head and neck with the presence of nodal disease traditionally results what 5 year overall survival?
50%
In well differentiated thyroid cancer, for what patient population dose the presence of nodal metastases not influence their overall stage or prognosis?
patients younger than 45
What pathologic nodal features have been associated with poor prognosis in head and neck cancer?
- Extracapsular spread (may not be true for HPV+ tumors)
- skipped nodal levels
- Involvement of IV and V
- Number of involved nodes
- Size of involved nodes
- Bilateral nodal disease
- Matted lymph nodes
What type of neck dissection is generally recommended for oral cavity cancer
Levels 1-3 at a minimum with level IV for oral tongue cancers. Bilateral dissection should be considered with floor of mouth, ventral tongue or midline tongue involvement in those undergoing elective ipsilateral neck dissection with no plans for postop radiation
What type of neck dissection is generally recommended for oropharyngeal cancer
Levels II-IV. Bilateral dissection considered for base of tongue tumors, posterior oropharynx tumors and those that cross midline. Dissecting level IIB in cN0 necks is controversial
What type of neck dissection is generally recommended for hypopharynx and laryngeal cancer
Levels II-IV and occasionally VI
What is the reported rate of marginal mandibular nerve injury after neck dissection (particularly level IB and occasionally level IIA) and what is most common post op HB score
Immediate: ~20%. Permanent: <5%
HB grade II-III/VI
What sequelae results from resection of spinal accessary nerve?
Shoulder syndrome: denervation of trapezius muscle resulting in destabilization of scapula and inability to abduct the shoulder >30 degrees, pain and shoulder girdle deformity. Injury from dissection around spinal accessory nerve in levels IIB and VA may also result in shoulder syndrome.
What nerve can be injured during dissection in level IV, which can result in paralysis of the ipsilateral hemidiaphragm?
Phrenic nerve
How should carotid artery exposure after neck dissection be dealt with?
Coverage with vascularaized tissue, preferably a mycutaneous flap
What sequelae can result from sacrifice of both internal jugular veins?
Facial and cerebral edema, increased intracranial pressure, AMS, SIADH, abducens palsy and blindness have all been associated
Prevalence of a persistent chylous fistula after neck dissection in level IV
1-3%. Most are in left neck, but 25% have been reported in right neck.
What is the normal volume of chyle that passes through the lymphatic duct per day and what does it contain?
2-4L/day. Fat (chylomicrons, long chain fats), protein, electrolytes and lymphocytes
What are the possible sequelae of a persistent chyle leak?
Hypovolemia, electrolyte disturbances, hypoalbuminemia, coagulopathy, immunosuppression, infection, peripheral edema, chylothorax
What can you test suspected chylous fluid for to confirm?
- Chylomicrons
- Triglycerides
- Sudan III stain positive
What are initial steps to treat chyle leak that is less than 500ml/day (low output)
- Low fat, medium chain fatty acid only diet
- Pressure dressing
- Suction wound drainage
What is the difference in impact on quality of life between a radial neck dissection and a modified radical neck dissection?
Radical neck dissection results in significantly worse shoulder function and a tend toward increased pain. No difference in subjective appearance, activity, recreation, chewing, swallowing or speech.
Boundaries of the oral cavity
Anterior: vermillion border of the lip
Posterior/superior: Hard and soft palate junction
Posterior/inferior: Circumvallate papillae
Lateral: Anterior tonsillar pillars and glossotonsillar folds
Primary oral cavity tumors of which two subsites have the highest risk for bony invasion?
- Alveolar ridges
- Retromolar trigone
Describe the course of the Wharton duct from the gland to the floor of the mouth and its relationship to the lingual nerve
Anterior “deep lobe” of the submandibular gland -> between the lingual and hypoglossal nerves over the hyoglossus muscle -> anterior and superior ascent between the genioglossus and sublingual glands -> over the lingual nerve -> sublingual papilla just lateral to the lingual frenulum
Arterial supply of the oral cavity
External carotid artery
- Lingual arter -> oral tongue
- Greater palatine artery -> hard palate
- Superior alveolar arteries -> gingiva of the maxilla, alveolar ridge, teeth, buccal mucosa
- Transverse facial artery (superficial temporal artery) -> buccal mucosa
- Facial artery -> lips (labial arteries)
- Buccal artery (maxillary a) -> buccal mucosa
- Inferior alveolar artery: mandible and mandibular teeth
- Ascending pharyngeal artery + lesser palatine arteries -> retromolar trigone, posterior floor of mouth
- Submental (facial artery) and sublingual (lingual artery) arteries -> floor of mouth
What is the relationship between the lingual artery and vein, hypoglossal nerve, and the hyoglossus and mylohyoid muscles?
From superficial to deep (or lateral to medial)
- Mylohyoid muscle
- Hypoglossal nerve and lingual vein
- Hypoglossus muscle
- Lingual artery
- Genioglossus
What nerves provide sensation to the upper and lower lips?
- Upper lip: infraorbital (V2)
- Lower lip: mental nerve (V3)
Sensory innervation of the retromolar trigone?
- Lesser palatine nerves
- Glossopharyngeal nerve
Sensory innervation of the tongue
- Anterior two thirds: general sensory - lingual nerve (V3), special sensory - chorda tympani via the lingual nerve
- Posterior 1/3: general and special sensory - Cn IX
Sensory innervation of the floor of the mouth
Lingual nerve
Sensory innervation to the hard palate
Nasopalatine nerve (V2) via the incisive canal
Four intrinsic and four extrinsic tongue muscles
Intrinsic: vertical, transverse, superior longitudinal, inferior longitudinal
Extrinsic: genioglossus, hyoglossus, palatoglossus, styloglossus
Which tongue muscle is not innervated by the hypoglossal nerve
Palatoglossus, innervated by pharyngeal branch of vagus
Buccal space boundaries
Denied medially by the buccinator muscle and its facia, the mandible inferiorly, the zygomatic arch superiorly, the risorius, zygomaticus major and levator labii superior muscles laterally, the orbicularis oris muscle anteriorly, and the anterior border of the masseter muscle and the parotid gland posteriorly
Masticator space
Defined by the layers of the deep cervical fascia as the split around the mandible and come back together at the ventral and dorsal borders of the mandibular ramus, thus enclosing the lateral pterygoid muscle and by the fascia surrounding the medial pterygoid, masseter and temporalis muscle
Why lymph nodes usually drain the oral cavity?
Levels I-III
What lymph node basins drain the lips?
- Submandibular lymph nodes (level IB) -> upper and lower lip
- Submental lymph nodes (level IA) -> lower lip, primarily midline lesions
- Preauricular, parotid, perifacial -> upper lip
Typical lymphatic drainage of the oral tongue?
- Tip -> submental lymph nodes (level IA)
- Ventral tongue -> submental and submandibular lymph nodes (Level IA and IB)
- Lateral tongue -> submandibular (level IB), jugulodigastric nodes (level IIA), directly to levels III and IV)
- Laterality of the lymphatic drainage of the oral tongue due to the lack of lymphatic anastomoses across the fibrous lingual septum is unique from the base of tongue
Lymph nodes primarily responsible for drainage of retromolar trigone
Upper jugular nodes (level IIA)
Lymphatic drainage of floor of mouth
Anterior -> level IA and IB (often bilateral)
Posterior -> level IIA (ipsilateral)
Lymphatic drainage of buccal mucosa
Levels IA and IB
Lymphatic drainage of hard palate
Levels I and II
During what week of embryogenesis does the parotid gland develop?
7th week
Where does the parotid gland originate during development and what is its relationship to the facial nerve?
Parotid gland originates at the site of the eventual duct orifice and grows in posterior direction. The facial nerve develops in an anterior direction and eventually becomes surrounded by parotid gland tissue.
What are the different types of acini in the salivary glands?
- Serous acinis: found in the parotid
- Mucinous acini: in the sublingual gland and minor salivary glands
- Mixed acini: in the submandibular gland
Describe the salivary gland duct system
An acinus is the main secretory component that is composed of a central lumen surrounded by acinar cells that produce saliva. Intercalated ducts form early connections between acini. Both acini and intercalated ducts are lined with myoepithelial cells that helps contract and propel saliva foraward. Intercalated ducts feed into larger striated ducts and then into exrectory ducts.
4 main parts of the salivary duct system (AISE) - acinar cells, intercalaed ducts, striated ducts, exretory ducts
Relationship of lymph nodes and the parotid gland
Lymph nodes develop within the pseudocapsule of the parotid gland leading to intraparotid lymph nodes. No other salivary gland has intraglandular lymph nodes. Most lymph nodes lie within the superficial lobe but can be present in both superficial and deep lobes.
Path of stenson duct
Originates from the superficial portion of the parotid gland, travels anteriorly on the masseter muscle and buccinator fat pad and then travels medially to pierce the buccinator muscle. Duct empties lateral to the second maxillary molar.
What facial layer forms the parotid fascia?
Parotid fascia is continuous with the superifical layer of the deep cervical fascia.
SMAS relationship to parotid fascia
It is just superficial
Autonomic nerve supply of the parotid glands
The parasympathetic nervous system suuplies the parotid via CN IX (lesser petrosal nerve). The sympathetic nervous system supplies the gland via the superior cervical ganglion
Path of parasympathetic innervation of patoid gland
Parasympathetics that are part of glossopharyngeal nerve (tympanic branch) enter middle ear through tympanic canaliculus as Jacobsons nerve. They exit middle ear cavity and travel through middle cranial fossa as lesser petrosal nerve which exits the skull base through the foramen ovale and travels to the otic ganglion. After synapsing in the otic ganglion postsynaptic fibers are carried via the auciculotemporal nerve to the parotid gland.
How does the parotid gland change histologically with age?
There is an increase in adipose cells in the parotid parenchyma with age
What nerve carries the parasympathetic supply to the submandibular gland
The chorda tympani via the lingual nerve
Secretomotor function of the submandibular and sublingual glands is controlled by which nerve?
Parasympathetic contribution of facial nerve (nervus intermedius) via the chorda tympani
What are the most common squamous cell carcinoma subtypes found within the oral cavity?
- Sarcomatoid carcinoma
- Basaloid carcinoma
- Verrucous carcinoma
Besides SCC what are the most common malignancies of the oral cavity?
- Lymphoma
- Minor salivary gland tumors
- Sarcoma
- Melanoma
Leukoplakia
- A premalignant lesion
- White plaque that cannot be wiped off
- lower risk of malignancy (<30%)
Erythroplakia
- A premalignant lesion
- Red plaque not associated with obvious cause
- Higher risk of malignant conversion compared to leukoplakia (<60%)
Lichen planus
- Premalignant lesion
- Lacy white pattern on mucosa or atrophic lesions (red and smooth) or errosive lesions (depressed margins, covered with fibrinous exudate)
- More common in women
- <1% 10 year conversion rate
What benign lesion manifests as a butterfly shaped ulceration commonly found at the hard soft palate junction and is associated with pressure injuries?
Necrotizing sialometaplasia
What benign lesion is commonly fond in mucosal or salivary tissue and may resemble SCC?
Pseudoepitheliomatous hyperplasia
What is the most common site of oral verrucous carcinoma?
Buccal mucosa
What is the most common location of oral tongue SCC?
Posterolateral oral tongue
What is the most common location of buccal mucosa SCC?
Adjacent to the third mandibular molar
When does the NCCN (2013) recommend PET/CT scan in the workup of oral cavity cancer?
Consider for stage III-IV disease
What pathologic features directly relate to prognosis in oral cavity cancer?
- Tumor thickness (>5mm= increased risk of occult nodal disease, decreased recurrence free and overall survical rates)
- Differentiation
- Angiolymphatic invasion
Which has a worse prognosis: upper or lower lip cancer?
Upper lip cancer tends to be more aggressive and to have early metastatic potential
When performing osteotomy for mandibulotomy which is preferable: straight or stepwise osteotomy? Median or paramedian placement?
- Stepwise mandibulotomy: provides better alignment and stability
- Paramedian: minimizes trauma to the genioglossus, geniohyoid, and digastric muscles
What radiation dose is typically given to uninvolved nodal levels at risk for occult disease in oral cavity cancer undergoing definitive radiation?
44-64 Gy
When should adjuvant radiation or chemorads begin ager surgical resection?
6 weeks or less (often around 3-4 weeks). Ideally all treatment will be completed within 12 weeks from diagnosis.
What is the recommended adjuvant radiation recommended for oral cavity cancer?
- Primary site: 60-66 Gy daily M-F for 6 weeks
- N+ levels: 60-66 Gy
- N- levels: 44-64 Gy
What is the reconstruction of choice for lower lip defects
- Less than one third: primary closure
- One third to two thirds: Abbe Estlander flap
- More than two thirds: Karapandzic flap, Webster-Bernard flap or radial forearm free flap with palmaris longus tendon
What local flap using the facial artery can be used to close intraoral defects?
Facial artery musculomucosal (FAMM) flap
In a patient with a floor of mouth or oral tongue tumor, resection followed by primary closure of a large defect can result in what long term compication?
Tethered tongue
What reconstructive options are best used to avoid trismus in defects of the buccal mucosa larger than 3cm in diameter?
Skin graft or free tissue transfer
What is the reconstruction of choice for patients with segmental resection of the anterior mandible?
Free tissue transfer with vascularized bone (i.e fibula free flap)
What anatomical structures enter the pharynx between the superior and middle pharyngeal constrictor muscles, just inferior to the tonsil?
Stylopharyngeus muscle, styloglossus muscle, stylohyoid ligament, glossopharyngeal nerve
What important fascial layer separates the tonsillar region from the parapharyngeal space?
buccopharyngeal fascia
Name the layers of the posterior pharyngeal wall
Mucosa -> superior pharyngeal constrictor muscle -> buccopharyngeal fascia -> retropharyngeal space (contains lateral fat pads and retropharyngeal nodes) -> alar fascia -> prevertebral fascia -> prevertebral muscles (laterally)/anterior longitudinal ligament (medially) -> vertebral bodies
Muscular components of the soft palate and their innervation
- Superior pharyngeal constrictor muscle (CN IX, X)
- Palatoglossus muscle (CN X)
- Palatopharyngeus muscle (CN X)
- Tensor veli palatini muscle ( CN V3)
- Levator veli palatini muscle (CN X)
- Uvular muscle (CN X)
Arterial supply to tonsils
Tonsillar branch of the ascending pharyngeal artery, descending palatine artery, tonsillar branch of the facial artery (primary arterial supply), dorsal lingual artery, ascending palatine artery
Arterial supply to base of tongue
Lingual artery and its branches
Arterial supply to soft palate
Lesser palatine artery (primary arterial supply), ascending pharyngeal artery, tonsillar branches from the dorsal lingual artery, ascending palatine artery
Describe the location of the internal carotid artery in relationship to the tonsil
- Posterolateral to the lateral oropharyngeal wall
- Separated from tonsil by superior constrictor and buccopharyngeal fascia
- On average, it is 1.4cm from the tonsillar fossa in a 1 year old and 2.5cm in an adult
Describe the venous outflow from the oropharynx
- Tonsil: tonsillar and pharyngeal plexus, lingual and facial veins
- Base of tongue: lingual and retromandibular veins
- Soft palate: pharyngeal and pterygoid plexus, external palatine vein
- Posterior pharyngeal wall: pharyngeal venous plexus
All drain to the jugular venous system
Which nerve supplies the pharyngeal plexus?
CN X, CN IX and sympathetic fibers from the superior cervical ganglion
Which lymph node basins are common sites of spread of otopharyngeal cancer?
Levels II, III and IV most commonly
In addition to levels II, III and IV what other lymph node group is at risk with tonsil, soft palate and posterior pharyngeal wall cancer?
Retropharyngeal nodes
Why do tumors of the base of tongue have a high risk of bilateral nodal disease?
Precollecting lymphatic channels on each side cross the midline to drain to the contralateral side (up to 30% at presentation). Level II is at highest risk for bilateral disease
Describe the lymphatic drainage of the soft palate
- Medial -> middle one third of the jugular chain (level III)
- Lateral -> retropharyngeal nodes
- Anterior -> hard palate -> submental and submandibular nodes (levels IA and IB)
Uvular lymphatics drain primarily to level IIA
Describe lymphatic drainage of posterior pharyngeal wall
Retropharyngeal nodes (up to 44%), levels II and III
What rare malignancy arising in the oropharynx is a poorly differentiated SCC or undifferentiated carcinoma associated with a reactive lymphoplasmacytic infiltration?
Lymphoepithelial carcinoma
What is the most common type of lymphoma found in the oropharynx?
Non-Hodgkin lymphoma. Diffuse large B cell lymphomas are the most common subtype
What % of extranodal head and neck lymphomas are found in Waldeyer ring?
36%
what malignant tumor can rarely arise from melanocytes in the mucosa of the oropharynx?
Mucosal melanoma
Common initial symptoms of oropharyngeal malignancy?
Odynophagia, dysphagia, bleeding, painless neck mass, globus, otalgia, bleeding
Tumors in which oropharyngeal subsite is most commonly diagnosed on visual inspection at earlier stages?
Soft palate. They generally occur on the anterior oropharyngeal surface of the soft palate
Tumor specific contraindications to transoral tumor resection for oropharyngeal tumor
- Invasion of skull base
- Invasion or encasement of great vessels
- Invasion of the mandible
- Confluent primary tumor and neck metastasis
- Tumor extension potential necessitating
T staging for HPV - oropharyngeal cancer
T1: tumor ≤2 cm in greatest dimension
T2: tumor >2 cm and ≤4 cm
T3: tumor >4 cm, or
tumor extension to lingual surface of epiglottis
T4: moderately or very advanced
T4a: moderately advanced local disease in which tumor invades any of the following:
larynx (except lingual surface of epiglottis), extrinsic muscles of the tongue (except palatoglossus within the oropharynx), medial pterygoid muscle, hard palate,
mandible
T4b: very advanced local disease in which tumor encases carotid artery or invades any of the following:
lateral pterygoid muscle, pterygoid plates, lateral nasopharynx, skull base
What radiation technique or modality is recommended for management of oropharyngeal tumors?
Intensity modulated radiation therapy (IMRT)
What surgical approach can be used for more extensive inferiorly located oropharyngeal tumors not amenable to transoral approaches and does not require mandibulotomy?
- Lateral pharyngotomy
- Transhyoid pharyngotomy
- Lingural release and pull through technique
What is the most common method used for reconstruction of oropharyngeal defects after transoral procedures?
None. The wound is allowed to heal by secondary intention
What might result if a large portion of the soft palate is resected and not reconstructed after surgery for oropharyngeal tumors?
Velopharyngeal insufficiency with nasopharyngeal reflux and hypernasal speech
What subsite forms a transition point between the supraglottis and hypopharynx, is considered a part of the supraglottis and often results in aggressive disease when involved by tumors?
“Marginal area”: Lateral wall of the aryepiglottic folds
Between the area of transition of the inferior pharyngeal constrictor muscle and the cricopharyngeus muscle is a potential area of weakness and spread of posterior hyopharyngeal wall tumors beyond the hyopharynx. What is the name of this area?
Killian triangle
Arterial supply to the hyopharynx
- External carotid artery
- Superior laryngeal artery (primary blood supply)
- Branches of the lingual artery
- Branches of the ascending pharyngeal artery
Venous drainage of hyopharynx
Through the pharyngeal plexus, adjacent names veins and jugular system
Sensory and motor innervation of the hyopharynx
- Sensory: Cn IX and X via the pharyngeal plexus; sympathetics from the pharyngeal plexus may also contribute
- Motor: CN X via the pharyngeal plexus
Which aerodigestive tract primary site has the highest prevalence of cervical nodal metastasis?
Hypopharynx (~70%)
Primary lymphatic drainage of the hypopharynx
Primarily drain to levels II-IV, also level VI (especially with inferior hyopharyngeal and post cricoid disease). Retropharyngeal nodes are also at risk
Three of the most common nonepithelial tumors that arise from the hyopharynx
- Lymphoma
- Sarcoma
- Adenocarcinoma
Where do adenocarcinomas of the hyopharynx arise?
Minor salivary glands or ectopic gastric mucosa
What is the risk of finding a second primary tumor in a patient with hyopharyngeal cancer?
Up to 18%
Explain why patients with hyopharyngeal tumors, particularly those located in the pyriform sinus develop referred otalgia.
Sensory fibers from the SLN and Arnold nerve both synapse within the jugular ganglion
T staging of the hyopharynx
T1: tumor limited to one subsite of hypopharynx (left or right pyriform sinuses, posterior hypopharyngeal wall, or postcricoid region), and/or tumor ≤2 cm in greatest dimension
T2: tumor extends into adjacent subsite of hypopharynx or adjacent site (larynx, oropharynx), and/or tumor >2 cm and ≤4 cm without fixation of hemilarynx
T3: tumor >4 cm, or clinical fixation of hemilarynx, or
extension to esophageal mucosa
T4: moderately advanced and very advanced local disease
T4a: moderately advanced local disease in which tumor invades one or more of the following:
thyroid cartilage, cricoid cartilage, hyoid bone, thyroid gland, esophageal muscle, central compartment soft tissue (prelaryngeal strap muscles and subcutaneous fat)
T4b: very advanced local disease in which tumor encases carotid artery or invades one or more of the following: mediastinal structures, prevertebral fascia
Which aerodigestive tract primary site has the lowest 5 year survival rate?
Hypopharynx (20-47%)
What levels should be addressed in an elective neck dissection for hypopharyngeal cancer?
Select neck dissection levels II-IV with inclusion of level VI in pyriform apex tumors and retropharyngeal lymph nodes in pharyngeal wall tumors
Recommened therapeutic neck dissection for hyopharyngeal cancer with clinical N+ ipsilateral neck?
Comprehensive neck dissection including levels I-V, inclusion of levels IV with pyriform apex tumots and retropharyngeal lymph nodes with pharyngeal wall tumors
An open partial pharyngectomy can be considered in patients with T1 and T2 hypopharyngeal tumors of the pyriform sinus. What are contraindications to this procedure?
- Tumor extension to more than one wall of pyriform sinus
- Involvement of pyriform apex
- Involvement of larynx including medial wall of pyriform sinus
An open partial laryngopharyngectomy combintes a classic hemilaryngectomy with a partial pharyngectomy and is used for what specific hypopharyngeal tumors?
Medial wall pyriform sinus tumors
Contraindications for conservation laryngeal surgery in patients with hypopharyngeal malignancy?
- Thyroid or circoid cartilage invasion
- Pyriform apex involvement
- Postcricoid region involvement
- Impared vocal cord mobility
What are the reconstructive options for circumferential defects of the hypopharynx?
- Tubed fasciocutaneous free flap
- Gastric transposition (gastric “pull up”)
- Colonic transposition
- Jejunal free flap
What anatomical structures form the superior and inferior limits of the cervical esophagus?
- Superior: cricopharyngeus muscle
- Inferior: thoracic inlet (sternal notch)
Layers of the cervical esophagus?
- Squamous epithelium
- Submucosa
- Inner circular muscle layer
- Outer longitudinal muscle layer
- Adventitia
Which section of the esophagus continues striated muscle? Smoth muscle?
- Upper one third: striated
- Middle one thrid: mixed
- Lower one third: smooth
What structures make up the upper esophageal sphincter?
- Posterior surface of the thyroid and cricoid cartilage
- Hyoid bone
- Cricopharyngeus muscle
- Inferior constrictor muscle (thyropharyngeus muscle)
- Cervical esophageal muscles
- Extends 3-4cm in total
The UES is tonically contracting via the vagus nerve
Arterial supply to the esophagus
- Upper esophageal sphincter and cervical esophagus: inferior thyroid artery
- Thoracic esophagus: aortic esophageal arteries, terminal bronchial arteries
- Distal esophagus and lower esophageal sphincter: left gastric artery, branch of the left phrenic artery
Venous drainage of cervical esophagus
Submucosal plexus -> superior vena cava
Innervation of the esophagus
- Sensory: CN X, IX and spinal afferent nerves
- Motor: CN X, parasympathetic and sympathetic nerves
- Intrinsic innervations: Auerbach plexus (between the inner circular and outer longitudinal muscle layers), Meissner plexus (submucosa)
What lymph node basins drain the cervical esophagus
Primarily levels II-IV, also drains to level VI, retroesophageal, retropharyngeal and superior mediastinal nodes (level VII)
What is the most common type of cervical esophgael cancer and distal esophageal cancer?
- Cervical: SCC
- Distal: adenocarcinoma
The cervical esophagus begins at approximately what distance from the incisors?
15cm to less than 20cm
What overexpression or gene amplification of what molecular marker has been associated with poor outcome in esophageal cancer?
Human epidermal growth factor receptor (HER-2)
Where is lingual nerve found during a submandibular gland excision?
Deep to the submandibular gland. With inferior retraction of the gland and anterior rectraction of the mylohyoid muscle, the lingal nerve and submandibular ganglion can be exposed.
What is the relationship of the lingual nerve to the submandibular duct in the floor of mouth?
The nerve courses from posteriolateral to anteriomedial position, passing inferior to Wharton duct
Where are facial artery and vein found in relation to the submandibular gland?
Facial vein is found on the lateral surface of the submandibular gland; the facial artery is located on the posterior surface of the gland and is often ligated on both the superior and inferior aspect of the gland during the submandibular gland excision.
Name the ducts through which the sublingual gland drains
The gland drains into the mouth via smaller duct of Rivinus (which empties into the floor of the mouth or into submandibular duct) and larger duct of Bartholin (empties into submandibular duct)
What structures border the sublingal gland?
Bordered by the mandible, genioglossus muscle and mylohyoid muscle
Where are most of the minor salivary glands located?
The hard palate mucosa harbors most of the mouth’s minor salivary glands
Functions of saliva
- Lubrication of food
- Buffering and prevention of carries
- Mineralization of teeth
- Antibacterial and bactericidal function
- Digestion
- Taste
Typically how large must a parapharyngeal mass be to visualize it intraorally?
Usually at least 3.5cm
What salivary gland is most susceptible to acute bacterial sialadenitits?
The parotid gland
What is the most commonly cultured organism in acute suppurative sialadenitis in hospitalized patients?
Staph aureus
Which salivary gland carries the highest risk for salivary calculi formation?
The submandibular gland is the most common as a result of increased calcium concentration, higher pH, more mucinous saliva and potential anatomical factors (length, gravity)
Which salivary calculi are most often radiopaque on standard xray?
Submandibular stones. 80% of parotid stones are radiolucent.
Patients with chronic sialadenitis should be monitored for what serious condition?
Patients with chronic sialadenitis are at an increased risk for salivary duct carcinoma
Side effects of anticholinergic medications
Urinary retention, increased body temperature, decreased persipiration, tachycardia, xerostomia, vision changes, confusion, respiratory suppression, mydriasis, constipation
What drug can be used to treat xerostomia?
Pilocarpine, a parasympathomimetic drug that acts on M3 acetylcholine muscarinic receptor
Mikulicz syndrome
Bilateral salivary gland swelling that is not associated with another systemic disease. Specially, it is distinct from salivary swelling associated with Sjogren syndrome
From what salivary gland does a ranula develop?
Ranulas are mucoceles that develop from the sublingual gland
Common appearance of ranula on physical exam
Often appear as bluish, translucent mass on floor of mouth.
Plunging ranula
A ranula that extends inferior to the mylohyoid muscle into the neck
Most common cause of nonsuppurative acute parotitis
The mumps virus
What family is the virust that causes mumps
Paramyxovirus (RNA)
Common initial symptoms of mumps?
Children between the ages of 5-10 with nonspecific symptoms of headache, fever, myalgia, anorexia, followed by bilateral parotid gland swelling
What is the pathophysiologic mechanism of Sjogren syndrome?
Autoimmune destruction of exocrine glands
Two broad classifications of Sjogren syndrome
Primary: involves only exocrine glands
Secondary: involves exocrine glands and additional connective tissue disease
Patients with Sjogren syndrome are at risk of developing what neoplasm?
lymphoma
What autoimmune disease is associated with primary mucosa associated lymphoid tissue or MALT lymphoma of the salivary glands?
Sjogren syndrome
What lab tests are frequently ordered for suspected Sjogrens?
SS-A and SS-B in addition to ANA, RF and ESR
A patient with multiple parotid cysts should be tested for what disease?
HIV
Initial symptoms of Kimura disease?
Diffuse lymphadenopathy, salivary gland swelling (parotid or submandibular), red cutaneous nodules on the head and neck as well as pigmented, coarse, pruritic skin overlying glandular swelling
Population most commonly affected by Kimura disease
Young males in their 20-30s from Southeast Asia
What inflammatory cell is most commonly elevated in Kimura disease?
Eosinophils (both peripheral eosinophilia and intralesional eosinophilia)
Aside from a CBC what other blood tests should be ordered in a patient with Kimura disease?
BUN, creatinine, urinary protein to rule out nephrotic syndrome.
Most common initial manifestation of necrotizing sialometaplasia
Ulcer on the posterior hard palate. The lesions of necrotizing sialometaplasia heal spontaneously in 5-9 weeks so treatment is supportive care only.
Heerfordt syndrome is an extrapulmonary form of what systemic disease?
Sarcoidosis
Characteristics of Heerfordt syndrome
Uveuoparotid fever presents with uveitis, non suppurative parotitis and in 50% of patients facial palsy. Treatment consists of systemic steroids and eye care.
How often does sarcoid affect salivary glands?
5-7% of sarcoid patients have salivary gland enlargement
Most common benign parotid tumor in children
Hemangiomas or pleomorphic adenomas
Most common benign salivary epithelial tumor in children
Pleomorphic adenomas
Recommended treatment for pleomorphic adenoma?
Surgical excision with a cuff of normal salivary tissue
Risk of malignant transformation of an unresected pleomorphic adenoma?
1.5% in first 5 years and 10% after 15 years
What risk factor is unique to Warthin tumor?
smoking
Which benign salivary tumor is most often bilateral?
Warthin tumor of parotid gland
The cells of a true oncocytoma contain an abundance of what organelle?
Mitochondria
Where are salivary monomorphic adenomas most commonly located?
Minor salivary glands of the upper lip
Monomorphic adenoma
A term that refers to a set of rare salivary gland tumors. includes basal cell adenoma, canalicular adenoma, clear cell adenoma, glycogen rich adenoma, myoepithelioma
Most common salivary gland malignancy in children?
Mucoepidermoid carcinoma
Risk factors associated with salivary gland cancer
Radiation exposure, history of head and neck cancer, EBV, HIV, Hodgkin disease, industrial exposure to rubber manufacturing or nickel compound, employment in a beauty salon
What is the incidence of cervical lymph node metastasis in a primary submandibular neoplasm?
30%
Which salivary gland malignancy has the highest rate of distant metastasis?
Adenoid cystic carcinoma. 30-50% of patients develop metastasis most commonly in the lungs
What is the most common presentation of carcinoma ex pleomorphic adenoma?
A male in his 60s-70s with a long standing parotid mass that suddenly increases in size over several months
What other cancer does salivary duct carcinoma histologically resemble?
High grade ductal carcinoma of the breast
What is the most common histologic subtype of malignant salivary gland tumors?
Mucoepidermoid carcinoma is most common malignant salivary gland tumor, followed by adenoid cystic carcinoma and then adenocarcinoma
What is the histologic appearance of low grade mucoepidermoid carcinoma?
Low grade is more cystic with little atypia and low mitotic activity. High grade is more solid.
Recommended treatment for low and high grade mucoepidermoid carcinoma?
Low grade requires removal of salivary gland with margin of healthy tissue, elective neck dissection is not necessarily required. High grade requires total excision and elective or therapeutic neck dissection and often adjuvant radiation.
What are the two main subtypes of malignant mixed tumor?
Carcinoma ex pleomorphic adenoma and carcinosarcoma
What is the most common manifestation o a polymorphous low grade adenocarcinoma?
An asymptomatic mass of the hard palate present for months to years
Clinicopathologic features of polymorphous low grade adenocarcinoma
Slow growth, indolent behavior, almost exclusively involves minor salivary glands with an infiltrative growth pattern and perineural invasion
Most important diagnosis to rule out when SCC is found in parotid gland?
Other primary (skin) with mets to parotid. This is more common than primary SCC of parotid gland.
What type of neck dissection whould a patient with node negative necks and high grade salivary gland malignancy have?
Selective neck dissection levels I-IV for a parotid primary and level I-III for submandibular primaries
Indications for adjuvant radiation therapy for salivary gland malignancies?
Cases of advanced stage positive margins after resection, high grade tumor, perineural invasion, or bony invasion
What are the reconstructive options after surgery for cervical esophageal cancer when resection includes the esophagus below the thoracic inlet?
- Gastric transposition (gastric “pull-up”)
- Colonic transposition
What are some of the disadvantages of the gastric transposition reconstruction for pharyngeal and esophageal defects?
- High morbidity and mortality
- Inability to close some defects with oropharyngeal or nasopharyngeal extension
- Frequent pulmonary complications
- Risk of hypoparathyroidism
- Gastric dumping syndrome
- Gastric outlet obstruction
- Regurgitation
What are the reconstructive options after surgery for cervical esophageal cancer when resection does not include the esophagus below the thoracic inlet?
- Gastric transposition
- Colonic transposition
- Jejunal vascularized free flap
- Tubed fasciocutaneous vascularized free flap
Boundaries of the larynx
-Superior: oropharynx; tip and lateral borders of the epiglottis
-Inferior: Trachea, plane passing through the inferior limit of cricoid cartilage
-Posterior/lateral: hypopharynx; laryngeal surface of the aryepiglottic folds, arytenoid region, interarytenoid space, mucus membrane covering posterior surface of cricoid cartilage
-Anterior: anterior/lingual surface of the suprahyoid epiglottis, thyrohyoid membrane, anterior commissure, thyroid cartilage, cricothyroid membrane, anterior arch of thyroid cartilage
Subsites of the larynx
-Supraglottis
- Glottis superior and inferior surface of TVF
- Subglottis: inferior margin of glottis to inferior border of cricoid cartilage
What subsite of the larynx arises from buccopharyngeal primordium (3rd or 4th branchial arches) and therefore derives arterial supply from superior laryngeal arteries and lymphatic drainage to levels II and III?
Supraglottis
What subsites of the larynx arise from the tracheobronchial primordium (6th branchial arch) and therefore derives arterial supply from inferior laryngeal arteries and lymphatic drainage to levels IV and VI?
Glottis and subglottis
What branchial arch gives rise to hyoid bone?
- 2nd: lesser horn and upper portion of hyoid bone
- 3rd: greater horn and lower portion of hyoid bone
Five subsites of supraglottis
- arytenoid cartilages
- suprahyoid epiglottis
- infrahyoid epiglottis
- aryepiglottic fold
- false vocal fold
Subsites of the glottis
TVFs (superior and inferior surface), including the anterior and posterior commissures
What are the subsites of the subglottis?
There are none
Normal histology of the supraglottis?
- Pseudostratified columnar respiratory epithelium
- Lateral surface of the aryepiglottic folds and epiglottis are stratified squamous epithelium
- Numerous mucinous glands are present
Type of epithelium of the glottis
Stratified squamous epithelium
Layers of the true vocal fold
- Stratified squamous epithelium
- Superficial lamina propria (Reinke space)
- Vocal ligament (intermediate and deep lamina propria)
- Thyroartenoid muscle
Normal histology of the subglottis
Pseudostratified columnar epithelium
What are the natural barriers to spread of laryngeal cancer?
- Quadrangular membrane
- Conus elasticus
- Thyrohyoid membrane (aperture for superior laryngeal neurovascular bundle allows spread)
- Laryngeal cartilages
- Hyoepiglottic ligament
- Anterior commissure tendon
- Cricothyroid membrane
Quadrangular membrane
Sheet of fibroelastic tissue stretching from the epiglottis to the arytenoid and corniculate cartilages, contributes to AE fold superiorly and defines free margin of false cord inferiorly
Conus elasticus
Sheet of fibroelastic tissue stretching from vocal ligament to superior margin of cricoid laterally and inferior margin of thyroid cartilage anteriorly (where it forms the cricothyroid membrane)
Anterior commissure tendon
Aka Broyles ligament. A fibrous tissue band that connects the vocal ligament to midline of thyroid cartilage and is associated with a lack of perichondrium at the insertion point and serves as a barrier to spread of laryngeal cancer
Pre-epiglottic space
Funnel shaped space formed by thyrohyoid membrane and thyroid cartilage anteriorly, epiglottis posteriorly, hyoepiglottic ligament, valecula and hyoid bone superiorly, and thyroepiglottic ligament inferiorly. Communicates laterally with the paraglottic spave and acts as an avenue for tumor spread.
Paraglottic space
Paired spaces definied by thyroid cartilage laterally, conus elasticus inferiomedially, ventricle medially, quadrangular membrane superiomedially, and pyriform sinus mucosa posteriorly. Avenue of spread of laryngeal cancer and communicates anteriorly with pre-epiglottic space.
What important feature of the infrahyoid epiglottic cartilage allows easy tumor growth into the pre-epiglottic space?
Fenestrations
Define the theoretical methods by which a laryngeal tumor can become transglottic (cross teh ventricle and involve the supraglottis and glottis and subglottis)
- Directly crossing the ventricle
- Crossing at the anterior commisure
- Via the paraglottic space
- Spread along thyroid cartilage to the posterior ventricle
Why do lateralized supraglottic tumors drain bilaterally?
The supraglottis is formed from a single structure (i.e. no midline fusion) and therefore lymphatics cross midline allowing bilateral spread of disease.
What is the inferior limit of the supraglottic lymphatic system within the larynx?
Inferior false vocal fold (barrier is the quadrangular membrane)
What nodal levels are most commonly involved by supraglottic tumors?
II, III, IV with bilateral disease common
What is the pathway for nodal spread from a supraglottic tumor to level II?
Along the superior laryngeal neurovascular bundle
What supraglottic subsite presents a high risk for aggressive behavior and early nodal metastases?
The “marginal zone”; suprahyoid epiglottis and superior aspect of the AE folds
What is the rate of occult nodal disease in supraglottic malignancies?
up to 40%. Increases with increasing T stage
Why do lateralized glottic tumors drain unilaterally?
They are formed by paired structures that fuse in midline. Lymphatics within this subsite are minimal and do not communicate across the midline.
What is the risk of occult nodal metastases in glottic carcinoma?
18%. Increases with T stage
What nodal levels are at risk for disease in glottic carcinoma?
II, II, IV and VI
What nodal levels are at highest risk for disease in subglottic carcinoman?
Level IV. Commonly present with contralateral or bilateral disease and mediastinal lymphadenopathy below level VII
What patient demographic is at highest risk for laryngeal cancer?
- Males (3.8:1)
- Tobacco exposure
- Age younger than 40
What are strongest risk factors for laryngeal carcinoma?
Alcohol and smoking
What percentage of laryngeal cancers have been associated with high risk HPV?
~25%
Four primary premalignant laryngeal lesions
- Hyperplasia
- Keratosis
- Dysplasia
- Carcinoma in situ
What is the approximate rate of dysplasia in laryngeal leukoplakia?
40%
What is approximate rate of malignant transformation of mild dysplasia, severe dysplasia or CIS?
- 11% for mild
- 30% for severe or CIS
- May take up to 10 years for malignant conversion but average of 3 years
Subtypes of SCC found in the larynx
- Verrucous
- Spindle cell (aka sarcomatoid carcinoma, carcinosarcoma, pseudosarcoma)
- Adenoid basaloid SCC
- clear cell carcinoma
- adenosquamous carcinoma
- giant cell carcinoma
- lymphoepithelial carcinoma
Pseudoepitheliomatous hyperplasia
Characterized by proliferation of the squamous mucosa, elongated rete ridges that appear worrisome for carcinoma and show no evidence of cytologic abnormalities consistent with malignancy. Can be associated with infection, trauma, granular cell tumor, chronic irritation. Easily mistaken for SCC.
What pathology of the larynx is associated with trauma and infarction of salivary gland tissue, is often misdiagnosed as SCC or mucoep and requires immunohistochemistry for diagnosis?
Necrotizing sialometaplasia
What subtype of SCC results in largely exophytic growth, pushing margins, does not metastasize, is associated with HPV 16 and 18 and has an indolent course?
Verrucous carcinoma. The larynx is the second most common site in the head and neck behind oral cavity.
What epithelial laryngeal cancer contains both basaloid and squamous components, cyst spaces, results in frequent regional and distant mets, occurs most commonly in the supraglottis and has a worse prognosis than standard SCC?
Basaloid SCC
What epithelial laryngeal cancer contains malignant squamous epithelium on it surface associated with a deeper malignant spingle cell carcinoma, is associated with tobacco and alcohol use and results commonly in regional mets and is relatively radioresistant?
Spindle cell carcinoma
What are the cells of origin for supraglottic adenocarcinoma?
Minor salivary glands
What are the two most common laryngeal malignant salivary gland cancers?
Mucoep and adenoid cystic
What is the relative occurrence of supraglottic neuroendocrine tumors in men and women?
They occur three time more commonly in women than in men
- this tumor type is very rare and usually lethal with a 2 and 5 year survival rate of 16% and 5%
What laryngeal tumors arise from ossified hyaline cartilage, most commonly from the cricoid cartilage?
Chondrosarcomas
What tumors most commonly metastasize from a distant site to the larynx?
Kidney, skin (melanoma), breast, lung, prostate, GI tract
What is the most common site of second primaries in patients with larynx cancer?
Lung
What is the most common initial symptom associated with supraglottic carcinoma?
Dysphagia. Can also manifest with dysphonia, odynophagia, otalgia, stridor, dyspnea, hemoptysis and neck mass
What are the most common initial symptoms associated with subglottic carcinoma?
Dyspnea and stridor
On endoscopy what findings may be suspicious for a laryngeal carcinoma?
Ulceration, sessile lesion, polpoid lesion, submucosal fullness, exophytic friable mass
When using MRI for the evaluation of a patient with laryngeal cancer, what modality or sequences would be most useful to determine invasion of the preepiglottic and/or paraglottic space?
T1-weighed gadolinium enhanced MRI with fat suppression. High negative predictive value. False positive results are caused by inflammation
What is the overall 5 year survival rate for laryngeal cancer and which subsite has the best overall survival?
- 64%
- glottic (79%) > supraglottic (47%) > subglottic (30-50%)
Why does involvement of anterior commissure decrease prognosis (local control rates) for both surgery and radiation therapy?
Inadequate recognition of deep extension
What factors increase the risk of peristomal recurrence after laryngectomy for laryngeal cancer?
- T3 or T4 tumors
- Subglottic tumor extension
What are the contraindications to transoral resection of laryngeal carcinoma?
- Subglottic extension (>5mm)
- Postcricoid extension
- Pyriform sinus invasion
- Cartilage invasion
- Tongue base involvement
Types of horizontal partial laryngectomies
- Supraglottic
- Extended supraglottic
- Supracricoid
What is the embryologic rationale behind horizontal hemilaryngectomy?
An embryologic boundary exists between the false and true vocal folds resulting in independent drainage pathways. A subset of T1/T2 supraglottic tumors that do not extend into neighboring structures may benefit from horizontal supraglottic hemilaryngectomy.
what sites are most commonly involved by distant metastases from the larynx?
Lung and mediastinum (not including level VII)
What subsite of the larynx has the highest risk factor for distant mets?
Supraglottis
What levels of the neck should be dissected during an elective neck dissection for an N0 supraglottic cancer
Levels II-IV, VI when appropriate
What is the initial treatment of an airway fire?
Remove the ETT, then irrigate with water, reintubate and perform bronchoscopy to survey the injury
What is the point of entrance into the larynx during laryngofissure?
The larynx is divided in the midline with entry at the anterior commissure
What are some common indications for salvage surgery after nonoperative primary management of laryngeal cancer?
- residual or recurrent locoregional disease
- Chondroradionecrosis
- Severe aspiration
- Laryngeal stenosis
- Pharyngoesophageal stenosis
In a patient undergoing laryngopharyngectomy with primary closure what additional procedure should be performed to decrease postoperative dysphagia?
Cricopharyngeal myotomy
What type if stitch is most frequently used for closure of laryngopharyngectomy?
- Running Connell stitch followed by one or two layers of interrupted 3.0 vicryl to imbricate the overlying layers
- Flood the mouth to ensure closure is water right
What is the most common reason for TEP valve failure?
Candida colonization
what is the long term incidence of hypothyroidism in patients treated primarily with radiation for laryngeal cancer?
70%
What are the boundaries that define the nasopharynx?
- Superior: sphenoid bone
- Anterior: choana
- Posterior: clivus, C1 and C2
- Inferior: soft palate
- Lateral: torus tubarius and Rosenmueller fossa
What skull base foramen define the lateral roof of the nasopharynx?
- Foramen lacerum (greater petrosal and deep petrosal nerves travel through this)
What space will be violated if a nasopharyngeal tumor extends laterally through the buccopharyngeal fascia?
- Parapharyngeal space
What space will be violated if a nasopharyngeal tumor extends laterally through the anterior surface of the lateral pterygoid muscle?
- Masticator space
What is the relationship between the internal carotid artery and the fossa of Rosenmuller?
The ICA lies immediately posterolateral to this space
What functional structure located on the posterior nasopharyngeal wall is formed by the movement of the superior constrictor muscle and the palatopharyngeal muscle?
Passavant ridge
What is the blood supply to the nasopharynx?
- Ascending pharyngeal artery (from the ECA)
- Sphenopalatine (internal maxillary artery)
- Vidian artery (internal maxillary artery)
What is the venous drainage system of the nasopharynx?
Pharyngeal plexus -> jugular system
Sensation of the nasopharynx is conveyed by what nerves?
- CN IX
- V2
What are the three subsites of the nasopharynx?
Lateral wall
Posterior wall
Soft palate
What is the most common site of distant metastasis for nasopharyngeal carcinomas?
Bone
What nodal levels are highest risk for metastases from nasopharyngeal carcinoma?
- Retropharyngeal nodes and levels II and VA
- Bilateral disease is common
What % of patients diagnosed with nasopharyngeal carcinoma develop nodal disease on physical exam or imaging?
80%
What are the nodes of Rouviere?
Lateral retropharyngeal lymph nodes; highest neck nodes, draines the sinuses and nasopharynx, enlargement can cause Vernet’s syndrome
What is the primary mode of EBV transmission?
Saliva
In which nasopharyngeal cell type is EBV infection a risk factor for the development of malignancy?
Pseudostratified columnar respiratory epithelium. It is carried for life by the infected person
What is the most common presenting clinical manifestation of nasopharyngeal carcinoma? What other symptoms are common?
- Lymphadenopathy (60%)
- Blood tinged saliva/sputum, more common than epistaxis
- Conductive hearing loss from serous otitis media
- Epistaxis
- Nasal obstruction
- Tinnitus
- Cranial nerve palsy
Petrosphenoidal syndrome
Tumor invasion of skull base with involvement of CN III-VI resulting in facial pain and diplopia
Thornwaldt cyst
A notochord remnant presenting as a benign cystic mass in the nasopharynx
a patient with locally advanced nasopharyngeal cancer complains of ipsilateral dry eye. Which nerve is most likely affected?
Vidian nerve
A patient with locally advance nasopharyngeal cancer has unilateral true VF paralysis, winged scapula and uvular deviation. What is the name of this syndrome
Vernet syndrome
- Refers to paralysis of the IX, X, and XI cranial nerves traversing the jugular foramen.
How often does nasopharyngeal carcinoma involve the skull base at time of diagnosis?
35%
What predicts a worse prognosis in nasopharyngeal cancer: prestyloid or poststyloid parapharyngeal extension?
Prestyloid
A patient is having seizures 4 years after primary radiation therapy for nasopharyngeal carcinoma. What is the likely diagnosis?
Temporal lobe necrosis
Fatigue and amenorrhea 6 years after radiation therapy are likely due to what late complication?
Hypopituitarism
The sphenopalatine artery enters the nasal cavity through the sphenopalatine foramen which is located where?
Lateral nasal wall just posterior to the end of the middle turbinate
Which nerve originates in the pterygopalatine fossa and innervates the hard palate?
Greater palatine
The name of what line from the medial canthus to the angle of the mandible carries significant prognostic value in sinonasal malignancies?
Ohngren line. Tumor limited to the anterior inferior portion portends better prognosis.
What are the anatomical boundaries of the pterygopalatine fossa?
A pyramidal space beneath the orbit that is bounded anterior by the posterior wall of the maxillary sinus and posteriorly by the pterygoid plates
Which nerves and what vessel run through the pterygopalatine fossa
sphenopalatine, lesser and greater palatine nerves, vidian nerve, internal maxillary artery
What is the most common site of sinonasal malignancy?
Maxillary sinus
Tumors in which paranasal sinus are associated with the highest rate of neurological sequelae?
Sphenoid sinus
what is the most common lymph node basin involved by metastatic sinonasal malignancy
Upper jugulodigastric
Most common type of sinonasal malignancy?
- SCC
Second most common type of sinonasal malignancy
Adenoid cystic carcinoma (cribiform is the most common type and has the best prognosis)
Most common location of sinonasal mucosal melanoma?
Lateral nasal wall including turbinates
Histologic features of esthesioneuroblastoma
- S100+
- Homer Wright rosettes
- Flexner Winter rosettes
what sinonasal tumors can be considered small round blue cell tumors?
- Esthesioneuroblastoma
- Rhabdomyosarcoma
- Sinonasal undifferentiated carcinoma
- Small cell carcinoma
- Neuroendorine carcinoma
- Plasmacytoma
- Poorly differentiated and nonkeratinizing SCC
- Lymphoma
- Mucosal melanoma
Histologic features of sinonasal small cell carcinoma?
- Small cell with scan cytoplasm and round hyperchromatic nuclei with absent or poorly visualized nucleoli
- Cells grow in clusters and commonly display extensive necrosis and hemorrhage
What is the most common pediatric sinonasal tumor?
Rhabdomyosarcoma
Alveolar type rhabdomyosarcoma is associated with what chromosomal translocation?
t(2;13)(q35;q14), PAX3-FKHR gene fusion
Hemangiopericytomas arise from what cell types?
Extracapillary pericytes (of Zimmerman)
Typical clinical features of sinonasal hemangiopericytomas?
Soft, slow growing tumors typically arising in the nasal cavity that occasionally metastasize. Most common presentation is nasal obstruction and epistaxis.
In what anatomical site are sinonasal angiosarcomas most frequently found?
Nasal cavity
Which type of tumor is most common to metastasize to the nose and paranasal sinuses?
Renal cell carcinoma
What is the most common sinonasal lymphoma in Western and Asian populations?
- Diffuse large B cell (Western)
- NK/T cell lymphoma (Asian)
Orbital apex syndrome
- Results in diplopia, decreased visual acuity and numbness above the eye
- Involves CN II, III, IV, V1 and VI
Superior orbital fissure syndrome
- results in ophthalmoplegia, periorbital numbness, ptosis, proptosis and fixed dilated pupil
- CN III, IV, V and VI are affected
A patient has unilateral nasal obstruction, eye proptosis and decreased sensation of his cheek. Which cranial nerve is affected?
V2
What is unique about the AJCC staging of head and neck mucosal melanomas?
All are considered T3 or T4 reflecting the aggressive behavior
What sinonasal sarcoma has the best prognosis?
Chondrosarcoma
which sinonasal malignancy has the worst prognosis?
Mucosal melanoma
Which sinonasal malignancy has the best prognosis?
Minor salivary gland tumors
What is a common postoperative complication of medial maxillectomy?
Epiphora or recurrent dacrocystitis from division of the nasolacrimal duct
What are the two most common head and neck locations for osteosarcoma?
Mandible and maxilla
Hemangiopericytomas arise most commonly from what head and neck site?
Sinonasal cavity
What is the most common head and neck site of origin of leiomyosarcoma?
The oral cavity
Most common head and neck site for chondrosarcoma?
Sinonasal cavity
What hereditary syndrome is caused by a mutation in p53 tumor suppressor gene resulting in greatly increased risk of sarcomas and other cancers?
Li Fraumeni syndrome
What condition is associated with half of all neurogenic sarcomas?
NF-1
Four histologic subtypes of rhabdomyosarcoma?
- Embryonal
- Alveolar (worst prognosis)
- Mixed
- Anaplastic (previously pleomorphic)
Treatment for rhabdomyosarcoma?
Chemotherapy typically used with radiation as an induction agent and then concurrently. Typically vincristine as main agent used with two other agents
What soft tissue sarcoma has the highest response rate to adjuvant radiation?
Liposarcoma
Most common head and neck sites of origin for synovial sarcoma
Hypopharynx and retropharynx
T staging for soft tissue sarcomas
T1: tumor <5cm in greatest dimensions (T1a superficial, T1b deep)
T2: tumor > 5cm in greatest dimensions (T2a superficial, T2b deep)
What is the classic initial symptom of angiosarcoma?
Unexplained bruising of the forehead or scalp, may progress in a rapid fashion in an elderly patient.
What % of angiosarcomas will occur in the head and neck region?
50%
Common history and findings in a patient with atypical fibroxanthoma
A rapidly enlarging, red, ulcerated lesion within the field of prior radiation treatment
- Management is with simple surgical excision. Nodal involvement is rare
In addition to the lymph nodes what anatomical sites should be considered for involvement in a patient with extranodal tonsillar non Hodgkin lymphoma?
20% of patients will have GI tract involvement
Between Hodgkin and non Hodgkin which is more likely to involve extranodal disease?
Non Hodgkin lymphoma
What is the primary risk factor for thyroid MALT lymphoma?
Hashimoto thyroiditis
Common cell markers for B cell lymphoma
CD20, CD22, CD79a
Tumor lysis syndrome
Hypocalcemia, hyperkalemia, hyperuricemia, hyperphosphatemia, acute renal failure days after initiation of chemotherpay for aggressive lymphoma
Mechanism of action of rituximab?
A monoclonal antibody against CD20
Indications for addition of chemotherapy to post op radiation
Positive surgical margins, distant mets, extranodal extension
What is the maximal length of bone that can be harvested with a fibula free flap?
25cm
Liklihood of neck metastasis in different oral cavity sites
Lip - 10% (don’t routinely do neck dissection)
Tongue - 40% (Neck dissection for T1 with depth of invasion greater than 4mm or T2+)
FOM - 30-50%
Alevolar ridge: 32% in lower and 14% in upper
Hard palate- 10-25%
RMT - 35-50% (behaves more like oropharyngeal sites)
Typically recommend neck dissection if liklihood of neck metastasis is grester than 20%
Reasons for persistent fistula
Abscess, forieng body, cancer, distal obstruction, epithelialization
Boundries of the parapharyngeal space
Superior: skull base
Inferior: hyoid
Lateral: mandibular ramus and angle
Medial: superior constrictors, tonsil, eustachian tube
Structures contained in the prestyoild parapharyngeal space
Internal maxillary artery, V3, salivary gland, muscle and connective tissue
Structures contained in the postsyloid parapharyngeal space
Carotid, CN IX-XII, sympathetic chain, lymph nodes in the periphery
Most common blood supply to Paraganglioma of the head and neck (i.e. carotid body tumor).
ascending pharyngeal
Two types of paragangliomas which can occur in the head and neck and how do you distinguish them on angiography
Carotid body tumor and glomus vagale. Carotid body tumor will show splaying of the internal and external carotid arteries (lyre sign)
Role of MRI in paraphyarngeal tumor imaging
- Can help determine if it is tonsillar or paraphayrngeal (which side of the superior constrictor is the mass on)
- Deep lobe of the parotid vs minor salivary gland
- Intracranial extension
- Vascular (flow voids) vs non vascular (can have a false negative)
Striated ducts of salivary duct
Contain the most mitochondria and are important for electrolyte activity. The richest in oxyphilic staining (deep red)
Theoretically which cell types of the salivary duct system give riseto which tumors
Acinar cells: acinic cell carcinoma
Intercalated ducts: pleomorphic adenoma
Striated ducts: warthins or oncocytoma
Excretory ducts: SCCA and mucoepidermoid carcinoma
Secondary sjogrens
Will have negative SSa and SSB but + HLA. Commonly have another autoimmune disease
what 2 salivary gland tumors will light up on technetium 99 scan
Warthin’s and oncocytoma (because of the high amount of mitochondria)
Advantages and disadvantages of sural vs great auricular nerve grafting for facial nerve injury
Sural: Advantage - length; Disadvantage - second site incision, anatomy, expertise
Great auric: Advantage - same site access, reasonable size match; Disadvantage- some length and size discrepancy (theoretical risk of adenoid cystic great auric carcinoma recurrence, if used when removing parotid for ACC)
Head and neck granulomatous diseases
- Mycobactal TB
- Atypical TB
- Sarcoid
- Deep fungal infection
- Actino and cat scratch can appear like granulomatous diseases on FNA due to their intense inflammatory processes but aren’t true granulomatous diseases
Sarcoid
- Often presents with hilar lymphadenopathy
- ACE levels are elevated
- In the head and neck lymphadenopathy is the most common manifestation
- Non caseating granulomas
Cellular pattern seen on HIV lymphadenopathy
follicular hyperplasia
