Salivary Gland TumorsMarka Crittenden M.D. Ph.D.

Anatomy Major GlandsParotid, submandibular and sublingual glandsMinor GlandsHundreds residing in the oral cavity, pharynx and paranasal sinuses.

?Major Salivary Glands

Parotid GlandBordersSuperior 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 mandibleFacial 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 GlandBordersLateral 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 Whartons duct in anterior floor of the mouthLymphatic Drainage Lvl I Lvl II- Lvl III

Sublingual Gland10% size of parotid glandLocated anterior floor of the mouthBordersLateral medial aspect of mandibleInferior mylohyoid muscleLingual nerve courses adjacent to sublingual glandDrain into the floor of the mouth through Rivinus ductsLymphatic drainage Lvl I- Lvl II- Lvl III

EpidemiologySalivary tumors 7% of head and neck tumorsParotid tumors 10x more common then submandibular and 100x more common then lingualParotid 80% benign (pleomorphic adenoma) Submandibular 50% malignantSublingual majority (65-88%) are malignantEqual incidence between sexesRisk Factors: nutritional deficiency, exposure to ionizing radiation, UV exposure, genetic predisposition, EBV

PathologyBenign TumorsPleomorphic AdenomasMalignant tumors Parotid mucopidermoid most common low grade, slow growing cured by surgery aloneSubmandibular and minor salivary adenoid cystic most common.

Adenoid CysticCribiform pattern differentiatedCribiform/solid pattern moderately differentiatedSolid Features undifferentiatedNatural history ranges from months to greater then 20 years.Lymph Node spread

Adenoid CysticPerineural spread common and can track along the cranial nerves back to the base of skull40% develop pulmonary mets but survival of 10-20 years can occur with pulmonary mets so primary must be managed

Metastatic Disease involving ParotidMechanismLymphatic spread most common from skinHematogenous spread - lungDirect extension skin or osseous sarcomas

StagingT1 2cm and no extraparenchymal extensionT2 > 2cm but not >4cm without extraparenchymal extensionT3 >4cm and or extraparenchymal extensionT4a invades skin, mandible, ear canal and/or facial nerveT4b invades skull base and or pterygoid plates and or encases carotid artery

Parotid TumorsClinical presentationAsymptomatic massCranial nerve palsey inability to move one side of face, one shoulder, one side of tongue.EvaluationTrismus to evaluate pterygoid involvementCT/MRI FNA in parotid tumors 90% sensitive and >95% specificNever perform incisional or excisional biopsy

Parotid TumorsLymph NodesRare in adenoid cystic 12% positive in clinically negative tumors.Size and grade are risk factors>4 cm 20% occult mets vs 4% in smaller tumorHigh grade 49% risk regardless of histologic type vs 7% for low or intermediateDistant SpreadLung 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# PTsFUP length (y)Prognastic factorsLC 5yS S/RSurv 5yS S/RMSKCC92S 10.5S/R 5.8Stage I/IIStage III/IVPositive nodesHigh-Grade79 9117 5140 6944 6396 829.5 5119 4928 57JH87All patients58 9259 75MDACC1557.5All patients58 8650-56 66-72PMH27110All patients -29 68 (RFS)

Submandibular tumorClinical presentationAsymptomatic massPainful mass as enlargesCranial nerve palsey decrease sensation in ipsilateral lower teeth, lip and gums, inability to move ipsilateral oral tongue or inbality to move part of face.EvaluationCT/MRI help to distinguish a pseudomassFNA in submandibular tumors useful only if reveals a malignancy. All lesions approached with a submandibular triangle dissectionAlmost never perform incisional or excisional biopsy.

Submandibular TumorsLymph Nodes28% risk in submandibular tumors Lvl I, II and III most common sitesDistant SpreadLung >bone and liver

Sublingual TumorsClinical presentationAsymptomatic swelling in floor of mouthCranial nerve palsey ipsilateral loss of sensation of one side of tongue.EvaluationCT/MRI Most tumors are malignant so FNA only useful if maligantAlways resect with a formal cancer surgery

Sublingual TumorsLymph NodesHigher risk of LN spread then parotid tumorsLvl I is first site of drainageDistant SpreadLung > bones and liver

TreatmentSurgery -Parotid90% confined to superficial lobe perform superficial parotidectomyIf adjacent to deep lobe - total parotidectomyIf invades adjacent soft tissue radical parotidectomyNever perform piecemeal excision in an attempt to preserve facial nerveNerve grafting can be performed and RT can start3-4 wk post op without adverse affectsFreys syndrome (gustatory sweating) due to redirection of parasympathetic and sympathetic nerve fibers to the dermal sweat glands

TreatmentSurgery - SubmandibularSmall tumor gland excisionECE En bloc resection with extended supraomohyoid neck dissectionSurgery SublingualSmall and localized can resect without submandibular glandGenerally requires resection of submandibular gland as well.

TreatmentRadiation Surgically unresectable tumorsEBRT with photon and or electrons with conventional or altered fractionationBrachytherapy EBRTNeutron therapy

TreatmentRadiation Surgically unresectable tumorsEBRTEquivalent control rates as for equivalent head and neck squamous cell cancersEarly stage 71-100% control ratesLate and Recurrent 50-70%HyperfractionationWang and Goodman reported on 14 patients using 1.6 Gy bid to 65-70 Gy.5 yr LCR 82%

TreatmentRadiation Surgically unresectable tumorsBrachytherapyUsed frequently with recurrent or advanced disease5 yr LCR 60%Neutron therapyBiologic effect of neutrons less effected by hypoxiaLethal effects less dependent on cell cycleRepair of sublethal damage in malignant cells is lessRBE > 2.6Severe late effect greater 17% versus 7%Improved local control but no diff in overall survival

TreatmentPostoperative Radiation IndicationsClose surgical margins (deep lobe parotid tumors, facial nerve sparing)Microscopically positive marginHigh grade including adenoid cysticInvolvement of skin, bone, nerve (gross or extensive perineural invasion), tumor extension beyond capsule with periglandular and soft tissue invasionLN spreadLarge tumors requiring radical resectionTumor spillageRecurrence

TreatmentPostoperative Radiation LCR with surgery and post op RTT1 100% T2 83% T3 80% T4 43%TechniqueParotid Electrons lateral en faceMixed beam 50-80% electron weighting lateral en face or wedge pair.Photons - wedge pair or IMRT

TreatmentTechniquePortal margins ParotidSuperior top of zygomatic boneInferior hyoid bone thyroid notchAnterior - 2cm ant to upper second molarPosterior posterior to mastoid tip.Lateral - 2 cm flash on cheekMedial 2 cm medial from ipsilateral oropharyngeal area.Electron portal margins are 1 cm greaterUsually 12 MeV- 16 MeV energy used

TreatmentTechniquePortal margins SubmandibularSuperior 1cm above upper border of tongueInferior Hyoid bone-thyroid notch interspaceAnterior anterior aspect of mental symphysisPosterior BOT- jugulodigastric nodal areaLateral 2 cm flash of ipsilateral mandibleMedial midline of tongue

TreatmentTechniquePortal margins SublingualSuperior 1cm above upper border of tongueInferior Hyoid bone-thyroid notch interspaceAnterior anterior aspect of mental symphysisPosterior posterior aspect of the ascending mandibular ramusLateral 2 cm flash of ipsilateral mandibleMedial 2cm past midline

TreatmentDosage Primary treatmentAccelerated fractionation with a delayed concomitant boostPhase I 1.8Gy daily to 36 GyPhase 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 GySpinal cord dose < 45 Gy. IMRT to 70 Gy for GTV 63 Gy CTV 1 and 56 Gy CTV2

TreatmentDosage Post op treatmentAdministered within 6 weeks of surgeryHigh 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 effectsSalivary fxn80% of saliva produced by major salivary glandsLoss of salivary fxn complete >35 GyDose limit to spare salivary function is 26 Gy. TrismusTMJ and masseter muscle < 50Gy. PT during and after treatment

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

Pleomorphic AdenomaBenign tumor 75% of all parotid epithelial tumors.Surgery is treament of choiceMultiply recurrent tumors can be treated with RT>3 local recurrencesLarge lesion with surgically inadequite marginMicroscopically positive surgical marginsMacroscopic residual diseaseMalignant transformation50-60 Gy dose

Minor Salivary TumorsHighest concentrations of the glands in the oral cavity, palate, nasal cavity and paranasal sinus500-700 GlandsNo glands located in the gingiva or anterior half of the hard palate50% malignantAdenoid cystic is most common malignant histology seen.

QuizWhat is the most common tumor of minor salivary glandsA. Pleiomorphic AdenomaB. Adenoid cystic carcinomaC. Mucoepidermoid carcinomaD. Squamous cell carcinoma

QuizWhat are the borders of the parotid gland?

SuperiorInferiorAnterior

PosteriorZyogomatic archHyoid boneAscending ramus of mandibleMastoid process

QuizThe most common parotid tumor is A. Pleomorphic adenomaB. Mucoepidermoid carcinomaC. Adenoid cystic carcinomaD. Detroit tigers

QuizMost parotid tumors are ___________A. Benign 60%B. Benign 80%C. Malignant 60%D. Malignant 80%

QuizAll of the following are true regarding adenoid cystic carcinoma except?A. It rarely spreads to Lymph nodesB. It is a common minor salivary tumorC. It typically does not involve nervesD. 40% develop pulmonary metastasis

QuizAdenoid cystic of parotid s/p parotidectomy with perineural invasion, what is treatment field?A. Post op bedB. Post op bed and BOSC. Post op bed and BOS and ipsilateral neckD. Post op bed and BOS and bilat neck

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

QuizHow are parotid tumors staged?T1T2T3T4 2cm2-4 cmExtraparenchymal, No VII involvement 4-6cm>6cm, BOS, CN VII

QuizAll of the following are indication for RT in pleiomorphic adenoma except?A. Deep lobe involvementB. Large >5cmC. Recurrent tumorD. Positive margin

QuizWhat seperates the superficial parotid from the deep lobe?Facial Nerve

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

QuizTrue/False series. Indication for post-op RT for parotid tumors

Close but clear margin on benign pleomorphic adenoma < 3cmAdenoid cystic with clear marginHigh grade mucopidermoidCN VII sacrifice for tumor close to nerve but not invading nerveFalse

True

True

False