Marka Crittenden M.D. Ph.D. Salivary Gland Tumors Marka Crittenden M.D. Ph.D.

Anatomy Major Glands Minor Glands Parotid, submandibular and sublingual glands Minor Glands Hundreds residing in the oral cavity, pharynx and paranasal sinuses.

Major Salivary Glands ? ? ?

Parotid Gland Borders Superior – zygomatic arch. Posterior – angle of mandible under earlobe toward the mastoid tip. Inferior – extends to the inferior aspect of the angle of mandible toward hyoid bone. Medial – borders of the parapharyngeal-base of skull. Lateral – below the skin of the preauricular cheek-upper neck. Anterior – wraps around ascending ramus of mandible Facial nerve divides the gland into the superficial (80 %) and deep lobe (20%) Parotid duct (Stensons) is 5 cm long and opens opposite the second molar. Lymphatic drainage – periparotid/intraparotid – lvl I – lvl II- lvl III. Accessory parotid lobe – Present in 20% of patients.

Submandibular Gland Borders Lateral – proximal half of the mandible. Posterior – anterior to but near the low anterior margin of the parotid gland. Inferior – approaches the level of the hyoid bone. Majority of gland lies over the external surface of the mylohyoid muscle. Lateral to and abuts the lingual and hypoglossal nerve and is medial to the marginal mandibular and cervical branch of the facial nerve. Drains through Wharton’s duct in anterior floor of the mouth Lymphatic Drainage Lvl I – Lvl II- Lvl III

Sublingual Gland 10% size of parotid gland Located anterior floor of the mouth Borders Lateral –medial aspect of mandible Inferior –mylohyoid muscle Lingual nerve courses adjacent to sublingual gland Drain into the floor of the mouth through Rivinus ducts Lymphatic drainage – Lvl I- Lvl II- Lvl III

Epidemiology Salivary tumors 7% of head and neck tumors Parotid tumors 10x more common then submandibular and 100x more common then lingual Parotid 80% benign (pleomorphic adenoma) Submandibular 50% malignant Sublingual majority (65-88%) are malignant Equal incidence between sexes Risk Factors: nutritional deficiency, exposure to ionizing radiation, UV exposure, genetic predisposition, EBV

Pathology Benign Tumors Malignant tumors Pleomorphic Adenomas Parotid – mucopidermoid most common – low grade, slow growing cured by surgery alone Submandibular and minor salivary – adenoid cystic most common.

Adenoid Cystic Cribiform pattern – differentiated Cribiform/solid pattern – moderately differentiated Solid Features – undifferentiated Natural history ranges from months to greater then 20 years. Lymph Node spread <5%

Adenoid Cystic Perineural spread common and can track along the cranial nerves back to the base of skull 40% develop pulmonary mets but survival of 10-20 years can occur with pulmonary mets so primary must be managed

Metastatic Disease involving Parotid Mechanism Lymphatic spread – most common from skin Hematogenous spread - lung Direct extension – skin or osseous sarcomas

Staging T1 ≤ 2cm and no extraparenchymal extension T2 > 2cm but not >4cm without extraparenchymal extension T3 >4cm and or extraparenchymal extension T4a invades skin, mandible, ear canal and/or facial nerve T4b invades skull base and or pterygoid plates and or encases carotid artery

Parotid Tumors Clinical presentation Evaluation Asymptomatic mass Cranial nerve palsey – inability to move one side of face, one shoulder, one side of tongue. Evaluation Trismus – to evaluate pterygoid involvement CT/MRI FNA in parotid tumors 90% sensitive and >95% specific Never perform incisional or excisional biopsy

Parotid Tumors Lymph Nodes Distant Spread Rare in adenoid cystic 12% positive in clinically negative tumors. Size and grade are risk factors >4 cm 20% occult mets vs 4% in smaller tumor High grade 49% risk regardless of histologic type vs 7% for low or intermediate Distant Spread Lung 25-35% risk for mucoepidermoid, adenoid cystic and malignant mixed tumors. Routine CXR

Postoperative Radiation versus Surgery for Salivary Gland Tumors: Results from the literature Series # PTs FUP length (y) Prognastic factors LC 5y S S/R Surv 5y S S/R MSKCC 92 S 10.5 S/R 5.8 Stage I/II Stage III/IV Positive nodes High-Grade 79 91 17 51 40 69 44 63 96 82 9.5 51 19 49 28 57 JH 87 All patients 58 92 59 75 MDACC 155 7.5 58 86 50-56 66-72 PMH 271 10 - 29 68 (RFS)

Submandibular tumor Clinical presentation Evaluation Asymptomatic mass Painful mass as enlarges Cranial nerve palsey –decrease sensation in ipsilateral lower teeth, lip and gums, inability to move ipsilateral oral tongue or inbality to move part of face. Evaluation CT/MRI – help to distinguish a pseudomass FNA in submandibular tumors useful only if reveals a malignancy. All lesions approached with a submandibular triangle dissection Almost never perform incisional or excisional biopsy.

Submandibular Tumors Lymph Nodes Distant Spread 28% risk in submandibular tumors Lvl I, II and III most common sites Distant Spread Lung >bone and liver

Sublingual Tumors Clinical presentation Evaluation Asymptomatic swelling in floor of mouth Cranial nerve palsey – ipsilateral loss of sensation of one side of tongue. Evaluation CT/MRI Most tumors are malignant so FNA only useful if maligant Always resect with a formal cancer surgery

Sublingual Tumors Lymph Nodes Distant Spread Higher risk of LN spread then parotid tumors Lvl I is first site of drainage Distant Spread Lung > bones and liver

Treatment Surgery -Parotid 90% confined to superficial lobe – perform superficial parotidectomy If adjacent to deep lobe - total parotidectomy If invades adjacent soft tissue – radical parotidectomy Never perform piecemeal excision in an attempt to preserve facial nerve Nerve grafting can be performed and RT can start3-4 wk post op without adverse affects Frey’s syndrome – (gustatory sweating) due to redirection of parasympathetic and sympathetic nerve fibers to the dermal sweat glands

Treatment Surgery - Submandibular Surgery – Sublingual Small tumor – gland excision ECE –En bloc resection with extended supraomohyoid neck dissection Surgery – Sublingual Small and localized can resect without submandibular gland Generally requires resection of submandibular gland as well.

Treatment Radiation – Surgically unresectable tumors EBRT with photon and or electrons with conventional or altered fractionation Brachytherapy ± EBRT Neutron therapy

Treatment Radiation – Surgically unresectable tumors EBRT Equivalent control rates as for equivalent head and neck squamous cell cancers Early stage 71-100% control rates Late and Recurrent 50-70% Hyperfractionation Wang and Goodman reported on 14 patients using 1.6 Gy bid to 65-70 Gy. 5 yr LCR 82%

Treatment Radiation – Surgically unresectable tumors Brachytherapy Used frequently with recurrent or advanced disease 5 yr LCR 60% Neutron therapy Biologic effect of neutrons less effected by hypoxia Lethal effects less dependent on cell cycle Repair of sublethal damage in malignant cells is less RBE > 2.6 Severe late effect greater 17% versus 7% Improved local control but no diff in overall survival

Treatment Postoperative Radiation Indications Close surgical margins (deep lobe parotid tumors, facial nerve sparing) Microscopically positive margin High grade including adenoid cystic Involvement of skin, bone, nerve (gross or extensive perineural invasion), tumor extension beyond capsule with periglandular and soft tissue invasion LN spread Large tumors requiring radical resection Tumor spillage Recurrence

Treatment Postoperative Radiation Technique LCR with surgery and post op RT T1 100% T2 83% T3 80% T4 43% Technique Parotid Electrons – lateral en face Mixed beam – 50-80% electron weighting lateral en face or wedge pair. Photons - wedge pair or IMRT

Treatment Technique Portal margins – Parotid Superior – top of zygomatic bone Inferior – hyoid bone – thyroid notch Anterior - 2cm ant to upper second molar Posterior – posterior to mastoid tip. Lateral - 2 cm flash on cheek Medial – 2 cm medial from ipsilateral oropharyngeal area. Electron portal margins are 1 cm greater Usually 12 MeV- 16 MeV energy used

Treatment Technique Portal margins – Submandibular Superior – 1cm above upper border of tongue Inferior – Hyoid bone-thyroid notch interspace Anterior – anterior aspect of mental symphysis Posterior – BOT- jugulodigastric nodal area Lateral – 2 cm flash of ipsilateral mandible Medial – midline of tongue

Treatment Technique Portal margins – Sublingual Superior – 1cm above upper border of tongue Inferior – Hyoid bone-thyroid notch interspace Anterior – anterior aspect of mental symphysis Posterior – posterior aspect of the ascending mandibular ramus Lateral – 2 cm flash of ipsilateral mandible Medial – 2cm past midline

Treatment Dosage – Primary treatment Accelerated fractionation with a delayed concomitant boost Phase I 1.8Gy daily to 36 Gy Phase II 1.8 Gy as in phase I in AM x 10 fractions to 54Gy and > 6hrs 1.6 Gy to GTVx 10 fractions to 16 Gy Spinal cord dose < 45 Gy. IMRT to 70 Gy for GTV 63 Gy CTV 1 and 56 Gy CTV2

Treatment Dosage – Post op treatment Administered within 6 weeks of surgery High Risk 2.0 Gy/fx to 60Gy and 1.8Gy/fx to 63Gy. Small volume known microscopic disease 66 Gy. Elective at risk 50 Gy (2.0Gy/fx) 54 Gy(1.8Gy/fx) Gross residual 70Gy.

Side effects Salivary fxn Trismus 80% of saliva produced by major salivary glands Loss of salivary fxn complete >35 Gy Dose limit to spare salivary function is 26 Gy. Trismus TMJ and masseter muscle < 50Gy. PT during and after treatment

Adenoid Cystic Carcinoma Post op RT always recommended Post op RT of entire pathway of adjacent cranial nerve to base of skull always recommended Regional LN spread is 15% and elective nodal irradiation is not standard Surgery alone LCR 25-40% +RT 75%-80%

Pleomorphic Adenoma Benign tumor – 75% of all parotid epithelial tumors. Surgery is treament of choice Multiply recurrent tumors can be treated with RT >3 local recurrences Large lesion with surgically inadequite margin Microscopically positive surgical margins Macroscopic residual disease Malignant transformation 50-60 Gy dose

Minor Salivary Tumors Highest concentrations of the glands in the oral cavity, palate, nasal cavity and paranasal sinus 500-700 Glands No glands located in the gingiva or anterior half of the hard palate 50% malignant Adenoid cystic is most common malignant histology seen.

Quiz What is the most common tumor of minor salivary glands A. Pleiomorphic Adenoma B. Adenoid cystic carcinoma C. Mucoepidermoid carcinoma D. Squamous cell carcinoma

Quiz What are the borders of the parotid gland? Superior Inferior Anterior Posterior Zyogomatic arch Hyoid bone Ascending ramus of mandible Mastoid process

Quiz The most common parotid tumor is A. Pleomorphic adenoma B. Mucoepidermoid carcinoma C. Adenoid cystic carcinoma D. Detroit tigers

Quiz Most parotid tumors are ___________ A. Benign 60% B. Benign 80% C. Malignant 60% D. Malignant 80%

Quiz All of the following are true regarding adenoid cystic carcinoma except? A. It rarely spreads to Lymph nodes B. It is a common minor salivary tumor C. It typically does not involve nerves D. 40% develop pulmonary metastasis

Quiz Adenoid cystic of parotid s/p parotidectomy with perineural invasion, what is treatment field? A. Post op bed B. Post op bed and BOS C. Post op bed and BOS and ipsilateral neck D. Post op bed and BOS and bilat neck

Quiz What is treatment of choice for cystic pleomorphic adenoma? After rupture or residual? Superficial parotidectomy. If intraop cystic rupture, add post op RT

Quiz How are parotid tumors staged? ≤ 2cm 2-4 cm Extraparenchymal, No VII involvement ± 4-6cm >6cm, BOS, CN VII

Quiz All of the following are indication for RT in pleiomorphic adenoma except? A. Deep lobe involvement B. Large >5cm C. Recurrent tumor D. Positive margin

Quiz What seperates the superficial parotid from the deep lobe? Facial Nerve

Quiz Intraparotid lymph node and a single 3cm neck node what is the most likely primary? Skin Parotid

Quiz True/False series. Indication for post-op RT for parotid tumors Close but clear margin on benign pleomorphic adenoma < 3cm Adenoid cystic with clear margin High grade mucopidermoid CN VII sacrifice for tumor close to nerve but not invading nerve