Core Features • Embryology of the salivary glands and their as- sociated structures • Detailed anatomy of the parotid, submandibular, sublingual, and minor salivary glands, including nervous innervation, arterial supply, and venous and lymphatic drainage • Histology and organization of the acini and duct systems within the salivary glands • Physiology and function of the glands with re- spect to the production of saliva • Considerations when taking a patient’s history • e intra- and extraoral aspects of inspection and palpation during a physical examination Chapter Anatomy, Function, and Evaluation of the Salivary Glands F. Christopher Holsinger and Dana T. Bui 1 1 Contents Introduction 2 Developmental Anatomy 2 Parotid Gland 2 Anatomy 2 Fascia 3 Stensen’s Duct 3 Neural Anatomy 4 Autonomic Nerve Innervation 4 Arterial Supply 5 Venous Drainage 6 Lymphatic Drainage 6 Parapharyngeal Space 6 Submandibular Gland 6 Anatomy 6 Fascia 6 Wharton’s Duct 7 Neural Anatomy 7 Arterial Supply 8 Venous Drainage 8 Lymphatic Drainage 8 Sublingual Gland 8 Minor Salivary Glands 9 Histology 9 Physiology of Salivary Glands 11 Evaluation of the Salivary Glands 13 History 13 Physical Examination 13 Radiologic and Endoscopic Examination of the Salivary Glands 14
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Thehumansalivaryglandsystemcanbedividedintotwodistinct exocrine groups . The major salivary glands in-cludethepairedparotid,submandibular,andsublingualglands .Additionally,themucosaoftheupperaerodiges-tive tract is lined by hundreds of small, minor salivary glands . The major function of the salivary glands is tosecrete saliva, which plays a significant role in lubrica-tion,digestion,immunity,andtheoverallmaintenanceofhomeostasiswithinthehumanbody .
Developmental Anatomy
In the last 15years, significant improvement has beenmade in our understanding of the molecular basis ofsalivaryglanddevelopment,supplantingandexpandingclassicalteachingintheembryologyanddevelopmentalanatomy .
Earlyworksuggeststhatdevelopmentofthesalivaryglandsbeginsduringthesixthtoeighthembryonicweekwhenoralectodermaloutpouchingsextendintothead-jacentmesodermandserveasthesiteoforiginformajorsalivaryglandgrowth .Thedevelopmentofmajorsalivaryglands is thought toconsistof threemainstages [1,8] .Thefirststageismarkedbythepresenceofaprimordialanlage(fromtheGermanverbanlagen,meaningtolayafoundationortoprepare)andtheformationofbranchedductbudsduetorepeatedepithelialcleftandbuddevel-opment . Ciliated epithelial cells form the lining of thelumina,whileexternalsurfacesare linedbyectodermalmyoepithelial cells [2] . The early appearance of lobulesand duct canalization occur during the second stage .Primitiveacinianddistalductregions,bothcontainingmyoepithelial cells, form within the seventh month ofembryoniclife .Thethirdstageismarkedbymaturationoftheaciniandintercalatedducts,aswellasthedimin-ishingprominenceofinterstitialconnectivetissue .
Thefirstoftheglandstoappear,duringthesixthges-tationalweek,istheprimordialparotid gland .Itdevelopsfromtheposteriorstomodeum,whichlaterallyelongatesinto solidcordsacross thedevelopingmassetermuscle .Thecordsthencanalizetoformducts,andaciniareformedat the distal ends . A capsule formed from the ambientmesenchymesurroundstheglandandassociatedlymphnodes[14] .Smallbudsappearinthefloorofthemouthlateraltothetongueduringthesixthweekofembryonic
lifeandextendposteriorlyaroundthemylohyoidmuscleinto the submandibular triangle . These buds eventuallydevelop into the submandibular glands . A capsule fromthesurroundingmesenchymeisfullydevelopedaroundtheglandbythethirdgestationalmonth[8] .Duringtheninth embryonic month, the sublingual gland anlage isformedfrommultipleendodermalepithelialbudsintheparalingualsulcusofthefloorofthemouth .Absenceofacapsuleisduetoinfiltrationoftheglandsbysublingualconnective tissue . Intraglandular lymph nodes and ma-jorductsalsodonotgenerallydevelopwithinsublingualglands .Upperrespiratoryectodermgivesrise tosimpletubuloacinarunits .Theydevelopintotheminor salivary glandsduringthe12thintrauterineweek[17] .
Recent work using murine models has shown thecomplexity of the underlying molecular events orches-trating classical embryological findings . Developmentof the salivary glands is an example of branching mor-phogenesis, a process fundamental to many developingorgans, including lung, mammary gland, pancreas, andkidney[12] .Branchingorgansdevelopacomplexarbo-rization and morphology through a program of repeti-tive,self-similarbranchingforkstocreatenewepithelialoutgrowths .Thedevelopmentalgrowthofamulticellularorgansuchasasalivaryglandisbasedonasetofinterde-pendentmechanismsandsignalingpathways .Theresult-ingexpressionofthesepathwaysisdynamic,organized,and changes correspondingly with each developmentalstage . The sonic hedgehog (Shh) signaling plays an es-sentialroleduringcraniofacialdevelopment[13] .Otherpathways,includingthefibroblastgrowthfactorfamilyofreceptorsandassociatedligands,havealsobeenshowntoplayacrucialrole[28] .
Parotid Gland
Anatomy
Thepairedparotidglandsarethelargestofthemajorsali-varyglandsandweigh,onaverage,15–30g .Located inthepreauricularregionandalongtheposteriorsurfaceofthemandible,eachparotidglandisdividedbythefacialnerve into a superficial lobe and a deep lobe (Fig .1 .1) .The superficial lobe, overlying the lateral surface of themasseter,isdefinedasthepartoftheglandlateraltothefacialnerve .Thedeep lobe ismedial to the facialnerveandlocatedbetweenthemastoidprocessofthetemporal
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boneandtheramusofthemandible .Mostbenignneo-plasmsarefoundwithinthesuperficial lobeandcanberemovedbyasuperficialparotidectomy .Tumorsarisinginthedeeplobeoftheparotidglandcangrowandextendlaterally, displacing the overlying superficial lobe with-out direct involvement . These parapharyngeal tumorscangrowinto“dumbbell-shaped”tumors,becausetheirgrowth is directed through the stylomandibular tunnel[5] .
Theparotidglandisboundedsuperiorlybythezygo-maticarch .Inferiorly,thetailoftheparotidglandextendsdownandabutstheanteromedialmarginofthesterno-cleidomastoidmuscle .This tailof theparotidglandex-tendsposteriorlyoverthesuperiorborderofthesterno-cleidomastoidmuscle toward themastoid tip .Thedeeplobeoftheparotidlieswithintheparapharyngealspace[10] .
Anaccessory parotid glandmayalsobepresent lyinganteriorlyoverthemassetermusclebetweentheparotidductandzygoma .Itsductsemptydirectlyintotheparotidductthroughonetributary .Accessoryglandulartissueishistologicallydistinct fromparotidtissue inthat itmaycontainmucinousacinar cells inaddition to the serousacinarcells[6] .
Fascia
Thedeepcervicalfasciacontinuessuperiorlytoformtheparotid fascia, which is split into superficial and deeplayers toenclose theparotidgland .Thethickersuperfi-cialfasciaisextendedsuperiorlyfromthemasseterandsternocleidomastoidmusclestothezygomaticarch .Thedeep layer extends to the stylomandibular ligament (or membrane), which separates the superficial and deeplobesoftheparotidgland .Thestylomandibularligamentisanimportantsurgicallandmarkwhenconsideringtheresection of deep lobe tumors . In fact, stylomandibulartenotomy [22] can be a crucial maneuver in providingexposure forenbloc resectionsofdeep-lobeparotidorother parapharyngeal space tumors . The parotid fasciaformsadenseinelasticcapsuleand,becauseitalsocoversthemassetermuscledeeply,cansometimesbereferredtoastheparotid masseteric fascia.
The great auricular nerve is a sensory branch of thecervical plexus, particularly C2 and C3, and innervatesthe posterior portion of the pinna and the lobule . Thenerveparallelstheexternaljugularveinalongthelateralsurfaceof the sternocleidomastoidmuscle to the tailoftheparotidgland,whereitsplitsintoanteriorandposte-riorbranches .Thegreatauricularnerveisofteninjuredduringparotidectomy,whichcanresultinlong-termsen-sory loss in the lobule . Harvesting of this nerve can beusedforfacialnervegraftingincertaincases .
The auriculotemporal nerve is a branch of the man-dibular nerve, the third inferior subdivision of the tri-geminalnerve(V3) .Afterexitingtheforamenovale,thenervetraversessuperiorlytoinnervatetheskinandscalpimmediatelyanteriortotheear .Itscourserunsparalleltothesuperficialtemporalvesselsandanteriortotheexter-nalauditorycanal .
Autonomic Nerve Innervation
The glossopharyngeal nerve (CNIX) provides visceralsecretory innervation to the parotid gland . The nervecarries preganglionic parasympathetic fibers from theinferior salivatory nucleus in the medulla through thejugular foramen (Fig .1 .2) . Distal to the inferior gan-glion, a small branch of CNIX (Jacobsen’s nerve) reen-ters theskull throughthe inferior tympaniccanaliculusand into the middle ear to form the tympanic plexus .Thepreganglionicfibers thencoursealongas the lesserpetrosalnerveintothemiddlecranialfossaandouttheforamen ovale to synapse in the otic ganglion . Postgan-glionicparasympatheticfibersexittheoticganglionbe-neaththemandibularnervetojointheauriculotemporalnerve in the infratemporal fossa .Thesefibers innervatetheparotidglandforthesecretionofsaliva .Postgangli-onic sympatheticfibers innervate salivaryglands, sweatglands,andcutaneousbloodvesselsthroughtheexternalcarotid plexus from the superior cervical ganglion . Ace-tylcholineservesas theneurotransmitter forbothpost-ganglionicsympatheticandparasympatheticfibers[10] .Thisphysiologiccoincidenceallowsforthedevelopmentof“gustatorysweating”(alsoknownasFrey’ssyndrome)
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followingparotidectomy[19,26] .Patientsdevelopsweat-ingandflushingoftheskinoverlyingtheparotidregionduring eating due to aberrant autonomic reinnervationofthesweatglandsbytheregeneratingparasympatheticfibers fromanyresidualparotidgland .Frey’s syndromemayoccurinasmanyas25–60%ofpatientspostopera-tively .TheriskforFrey’ssyndromecanbeminimizedfirstby complete and meticulous superficial parotidectomy .Second, by developing skin flaps of appropriate thick-ness,exposedapocrineglandsof theskinareprotectedfromingrowthandstimulationbytheseveredbranchesoftheauriculotemporalnerveandtheirparasympatheticstimulationduringmeals .Therearenumerousnonsurgi-calandsurgicaltreatmentsforpersistentFrey’ssyndromefollowing parotidectomy (see Chapter5, Treatment ofFrey’sSyndrome) .
Arterial Supply
Thebloodsupplytotheparotidglandis frombranchesof the external carotid artery, which courses superiorlyfromthecarotidbifurcationandparalleltothemandibleundertheposteriorbellyofthedigastricmuscle .Thear-tery then travels medial to the parotid gland and splitsinto two terminal branches . The superficial temporal artery runs superiorly from the superior portion of theparotidgland to thescalpwithin thesuperiorpretragalregion . The maxillary artery leaves the medial portionof theparotidand supplies the infratemporal fossaandthepterygopalatinefossa .Duringradicalparotidectomy,thisvesselmustbecontrolledespeciallywhenmarginalorsegmentalmandibulectomyisrequired .Thetransverse facial arterybranchesoffthesuperficialtemporalarteryandrunsanteriorlybetweenthezygomaandparotidducttosupply theparotidgland,parotidduct,andthemas-setermuscle[10] .
The retromandibular vein, formed by the union of themaxillary vein and the superficial temporal vein, runsthrough the parotid gland just deep to the facial nerveto join the external jugular vein . There is substantialvariationinthesurgicalanatomyoftheretromandibularvein,whichmaybifurcateintoananteriorandposteriorbranch .Theanterior branchcanunitewiththeposteriorfacial vein, forming the common facial vein . The pos-terior facial vein lies immediately deep to the marginalmandibular branch of the facial nerve and is thereforeoftenusedasa landmarkfor identificationof thenervebranch,especiallyattheantegonialnotchofthemandiblewherethenervedipsinferiorly[3] .Theposterior branch of the retromandibular veinmaycombinewiththepost-auricularveinabovethesternocleidomastoidmuscleanddrainintotheexternaljugularvein .
Lymphatic Drainage
Contrarytothelymphaticdrainageoftheothersalivaryglands,thereisahighdensityoflymphnodeswithinandaroundtheparotidgland .Theparotidistheonlysalivaryglandwithtwonodallayers,bothofwhichdrainintothesuperficial and deep cervical lymph systems . Approxi-mately90%ofthenodesarelocatedinthesuperficiallayerbetweentheglandulartissueanditscapsule .Theparotidgland,externalauditorycanal,pinna,scalp,eyelids,andlacrimalglandsarealldrainedbythesesuperficialnodes .Thedeeplayerofnodesdrainsthegland,externalaudi-torycanal,middleear,nasopharynx,andsoftpalate[7] .
Parapharyngeal Space
Tumors of the deep parotid lobe often extend mediallyintotheparapharyngealspace(PPS) .Thisspacejustpos-teriortotheinfratemporalfossaisshapedlikeaninvertedpyramid .Thegreatercornuof thehyoidboneservesastheapexandthepetrousboneoftheskullbaseactsasthepyramidalbase .ThePPSisboundmediallybythelateral pharyngeal wall,whichconsistsofthesuperiorconstric-tor muscles, the buccopharyngeal fascia and the tensorvelipalatine .Theramusofthemandibleandthemedialpterygoidmusclemakeupthe lateralborder .Thepara-pharyngealspaceisborderedanteriorlybythepterygoidfascia and the pterygomandibular raphe . The posterior
Alinefromthestyloidprocesstothemedialportionofthemedialpterygoidplatedividestheparapharyngealspace into two compartments . The prestyloid compart-mentcontainsthedeeplobeoftheparotidgland,minorsalivary glands, as well as neurovascular structures, in-cludingtheinternalmaxillaryartery,ascendingpharyn-gealartery,theinferioralveolarnerve,thelingualnerve,andtheauriculotemporalnerve .Thepoststyloid compart-mentcontainstheinternaljugularvein,carotidarteryandvagusnervewithinthecarotidsheath,aswellascranialnervesIX, X, XI, and XII and the cervical sympatheticchain . Neurogenic tumors or paragangliomas from thecervicalsympatheticsorcranialnervescanthusariseinthiscompartment[4] .
Submandibular Gland
Anatomy
Thesubmandibulargland(inoldertexts,thisglandwassometimesreferredtoas“thesubmaxillarygland”)isthesecond largest major salivary gland and weighs 7–16g(Fig .1 .3) .Theglandislocatedinthesubmandibular tri-angle,whichhasasuperiorboundaryformedbytheinfe-rioredgeofthemandibleandinferiorboundariesformedbytheanteriorandposteriorbelliesofthedigastricmus-cle .Alsolyingwithinthetrianglearethesubmandibularlymphnodes, facialarteryandvein,mylohyoidmuscle,andthelingual,hypoglossal,andmylohyoidnerves .Mostofthesubmandibularglandliesposterolateraltothemy-lohyoidmuscle .Duringneckdissectionorsubmandibu-larglandexcision,thismylohyoidmusclemustbegentlyretractedanteriorlytoexposethelingualnerveandsub-mandibularganglion .Often,smaller,tongue-likeprojec-tionsof thegland follow theduct, as it ascends towardtheoralcavity,deeptothemylohyoidmuscle[29] .How-ever,theseprojectionsshouldbedistinguishedfromthesublingual gland which lies superior to the mylohyloidmuscle .(Formoredetail,seeChapter21,ManagementofTumorsoftheSubmandibularandSublingualGlands .)
causethemarginalmandibularbranchofthefacialnerveissuperficialtoit,andcaremustbetakentopreservethenerveduringsurgeryinthesubmandibularregion .Thus,divisionofthesubmandibularglandfascia,whenonco-logically appropriate, is a reliablemethodofpreservingandprotectingthemarginalmandibularbranchofthefa-cialnerveduringneckdissectionand/orsubmandibularglandresection .
Wharton’s Duct
The submandibular gland has both mucous and serouscellsthatemptyintoductules,whichinturnemptyintothe submandibular duct . The duct exits anteriorly fromthesublingualaspectofthegland,coursingdeeptothelingualnerveandmedialtothesublingualgland .Iteven-tuallyformsWharton’sductbetweenthehyoglossusandmylohyoid muscles on the genioglossus muscle . Whar-ton’sduct,themainexcretoryductofthesubmandibulargland,isapproximately4–5cmlong,runningsuperiortothehypoglossalnervewhileinferiortothelingualnerve .Itemptieslateraltothelingualfrenulumthroughapapillainthefloorofthemouthbehindthelowerincisortooth .Theopeningsforthesublingualgland,orthesublingual caruncles,arelocatednearthemidlineofthesublingualfoldintheventraltongue .
Neural Anatomy
Both the submandibular and the sublingual glands areinnervatedbythesecretomotorfibersofthefacialnerve(CNVII) .Parasympatheticinnervationfromthesuperior salivatory nucleus in the pons passes through the ner-vus intermediusand into the internalauditorycanal tojointhefacialnerve .Thefibersarenextconveyedbythechorda tympani nerveinthemastoidsegmentofCNVII,whichtravelsthroughthemiddleearandpetrotympanicfissure to the infratemporal fossa . The lingual nerve, abranchof themarginalmandibulardivisionof thefifthcranialnerve(CNV),thencarriesthepresynapticfibersto the submandibular ganglion . The postsynaptic nerveleavesthegangliontoinnervateboththesubmandibularandsublingualglandstosecretewaterysaliva .Asintheparotidgland,sympatheticinnervationfromthesuperior cervical ganglion accompanies the lingual artery to thesubmandibulartissueandcausesglandularproductionofmucoidsalivainstead[5] .
The lingual nervebranchesoffthemandibulardivi-sion of the trigeminalnerve (V3) in the infratemporalfossatosupplygeneralsensationandtastetotheante-riortwothirdsofthetongue .Thenervecourseslaterallybetweenthemedialpterygoidmuscleandramusofthemandible and enters the oral cavity at the lower thirdmolar to then travel across the hyoglossus along the
floorofthemouthinasubmucosalplane .Beneaththemandible, a small motor nerve branches off and trav-els posteriorly from the lingual nerve to innervate themylohyoid muscle . These fibers are usually sacrificedduring surgical removal of the submandibular gland .Parasympatheticfibersarecarriedviathelingualnervetothesubmandibularganglion,andpostsynapticfibersexitalongthecourseofthesubmandibularducttoin-nervatethegland .
Thehypoglossalnerve(CNXII)suppliesmotorinner-vationtoallextrinsicandintrinsicmusclesofthetongueexceptforthepalatoglossusmuscle .Fromthehypoglos-salcanalatthebaseoftheskull, thenerveispulledin-feriorly during embryonic development down into theneck by the occipital branch of the external carotid ar-tery .Fromhere,thehypoglossalnervetravelsjustdeeptotheposteriorbellyofthedigastricmuscleandcommontendonuntilitreachesthesubmandibulartriangle .HereCNXIIliesdeepinthetrianglecoveredbyathinlayeroffascia .Itslocationisanterior,deepandmedialrelativetothesubmandibulargland .Typicallythenervehasacloserelationshiptotheanteriorbellyofthedigastricmuscle .Itthenascendsanteriortothelingualnerveanditsgenudeep to the mylohyoid muscle . Extreme care should betakentopreservethisimportantnerveduringheadandnecksurgery .
Arterial Supply
Boththesubmandibularandsublingualglandsaresup-pliedbythesubmentaland sublingual arteries,branchesofthelingualandfacialarteries .Thefacial artery,thetor-tuousbranchof theexternal carotidartery, is themainarterialbloodsupplyofthesubmandibulargland .Itrunsmedialtotheposteriorbellyofthedigastricmuscleandthenhooksovertocoursesuperiorlydeeptothegland .Thearteryexitsatthesuperiorborderoftheglandandthe inferior aspect of the mandible known as the facial notch .Itthenrunssuperiorlyandadjacenttotheinferiorbranches of the facial nerve into the face . During sub-mandibularglandresection,thearterymustbesacrificedtwice, first at the inferior border of the mandible andagainjustsuperiortotheposteriorbellyofthedigastricmuscle .Thelingual arterybranchesinferiortoorwiththefacialarteryofftheexternalcarotidartery . Itrunsdeepto the digastric muscle along the lateral surface of themiddleconstrictorandthencoursesanteriorandmedialtothehyoglossusmuscle .
Venous Drainage
The submandibular gland is mainly drained by the an-terior facial vein,whichisincloseapproximationtothefacialarteryasitrunsinferiorlyandposteriorlyfromthefacetotheinferioraspectofthemandible .Becauseitliesjustdeeptothemarginalmandibulardivisionofthefacialnerve,ligationandsuperiorretractionoftheanteriorfa-cialveincanhelppreservethisbranchofthefacialnerveduringsubmandibularglandsurgery . It formsextensiveanastomoseswiththeinfraorbitalandsuperiorophthal-micveins .Thecommon facial veinisformedbytheunionoftheanteriorandposteriorfacialveinsoverthemiddleaspectofthegland .Thecommonfacialveinthencourseslateraltotheglandandexitsthesubmandibulartriangletojointheinternaljugularvein .
Lymphatic Drainage
Theprevascularandpostvascularlymphnodesdrainingthesubmandibularglandare locatedbetweentheglandanditsfascia,butarenotembeddedintheglandulartis-sue .They lie incloseapproximation to the facialarteryandveinat the superioraspectof theglandandemptyintothedeepcervicalandjugularchains .Thesenodesarefrequentlyassociatedwithcancersintheoralcavity,es-peciallyinthebuccalmucosaandthefloorofthemouth .Thus, when ligating the facial artery and its associatedplexusofveins,greatercaremustbetakennotonlytore-sectallassociatedlymphoadiposetissue,butalsotopre-servethemarginalmandibularbranchofthefacialnerve,whichrunsincloseproximitytothesestructures .
Sublingual Gland
Thesmallestofthemajorsalivaryglandsisthesublingualgland,weighing2–4g .Consistingmainlyofmucousaci-narcells,itliesasaflatstructureinasubmucosalplanewithintheanteriorfloorofthemouth,superiortothemy-lohyoidmuscleanddeeptothesublingualfoldsoppositethelingualfrenulum[11] .Lateraltoitarethemandibleandgenioglossusmuscle .Thereisnotruefascialcapsulesurroundingthegland,whichisinsteadcoveredbyoralmucosaonitssuperioraspect .Severalducts(of Rivinus)fromthesuperiorportionofthesublingualglandeithersecrete directly into the floor of mouth, or empty intoBartholin’s ductthatthencontinuesintoWharton’sduct .
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Both the sympathetic and parasympathetic nervoussystemsinnervatethesublingualgland .Thepresynapticparasympathetic(secretomotor)fibersofthefacial nervearecarriedbythechordatympaninervetosynapseinthesubmandibularganglion .Postganglionicfibersthenexitthesubmandibular ganglionandjointhelingualnervetosupply the sublingual gland . Sympathetic nerves inner-vatingtheglandtravelfromthecervical ganglionwiththefacialartery[5] .
Bloodissuppliedtothesublingualglandbythesub-mental and sublingual arteries,branchesofthelingualandfacialarteries,respectively .Thevenousdrainageparallelsthecorrespondingarterialsupply .Thesublingualglandismainlydrainedbythesubmandibularlymphnodes .
Ranulasarecystsormucocelesofthesublingualgland,and they can exist either simply within the sublingualspace or plunging posteriorly to the mylohyoid muscleintotheneck .Asimpleranulawillmostcommonlypres-entasabluish,nontendermassinthefloorofthemouthand may either be a retention cyst or an extravasationpseudocyst . A plunging ranula will present as a soft,painless cervical mass and is always an extravasationpseudocyst (see Chapter10, Management of MucoceleandRanula) .
Minor Salivary Glands
About 600 to 1,000 minor salivary glands, ranging insize from 1 to 5mm, line the oral cavity and orophar-ynx .Thegreatestnumberoftheseglandsareinthelips,tongue, buccal mucosa, and palate, although they canalsobefoundalongthetonsils,supraglottis,andparana-salsinuses .Eachglandhasasingleductwhichsecretes,directlyintotheoralcavity,salivawhichcanbeeitherse-rous,mucous,ormixed .
Postganglionic parasympathetic innervation arisesmainlyfromthelingual nerve .Thepalatinenerves,how-ever, exit the sphenopalatine ganglion to innervate thesuperiorpalatalglands .Theoralcavityregionitselfdeter-minesthebloodsupplyandvenousandlymphaticdrain-ageoftheglands .Anyofthesesitescanalsobethesourceofglandulartumors[11] .
ducts)andstroma(thesurroundingconnectivetissuethatpenetratesanddividestheglandintolobules) .Secretoryproductsaresynthesizedintracellularlyandsubsequentlyreleasedfromsecretorygranulesbyvariousmechanisms .Glandsareusuallyclassifiedintotwomaingroups .Endo-crine glandscontainnoducts,andthesecretoryproductsare released directly into the bloodstream or lymphaticsystem .Incontrast,exocrine glandssecretetheirproductsthroughaductsystemthatconnectsthemtotheadjacentexternalorinternalepithelialsurfaces .Salivaryglandsareclassified as exocrine glands that secrete saliva throughducts from a flask-like, blind-ended secretory structurecalledthe salivary acinus.
Theacinusitselfcanbedividedintothreemaintypes .Serous aciniinsalivaryglandsareroughlysphericalandrelease via exocytosis a watery protein secretion that isminimally glycosylated or nonglycosylated from secre-tory(orzymogen)granules .Theacinarcellscomprisingtheacinusarepyramidal,withbasallylocatednucleisur-roundedbydensecytoplasmandsecretorygranulesthataremostabundantintheapex .Mucinous acinistoreavis-cous,slimyglycoprotein(mucin)withinsecretorygran-ulesthatbecomehydratedwhenreleasedtoformmucus .Mucinous acinar cells are commonly simple columnarcellswithflattened,basallysituatednucleiandwater-solu-blegranulesthatmaketheintracellularcytoplasmappearclear .Mixed,orseromucous,acinicontaincomponentsofbothtypes,butonetypeofsecretoryunitmaydominate .Mixedsecretoryunitsarecommonlyobservedasserousdemilunes(orhalf-moons)cappingmucinousacini .
Between the epithelial cells and basal lamina of theacinus,flatmyoepithelial cells(orbasketcells)formalat-ticeworkandpossesscytoplasmicfilamentsontheirbasalside toaid incontraction,and thus forcedsecretion,oftheacinus .Myoepithelialcellsarealsoobservedaroundintercalatedducts,butheretheyaremorespindleshaped[16] .
Electrolyte modification and transportation of salivaarecarriedoutbythedifferentsegmentsofthesalivarygland’s duct system (Fig .1 .4) . The acini first secretethrough small canaliculi into the intercalated ducts,whichinturnemptyintostriatedductswithintheglan-dularlobule .Theintercalatedductiscomprisedofanir-regularmyoepithelial cell layer linedwith squamousorlow cuboidal epithelium . Bicarbonate is secreted intowhilechlorideisabsorbedfromtheacinarproductwithintheintercalatedductsegment .Striatedductshavedistin-guishingbasalstriationsduetomembraneinvaginationand mitochondria and are lined by a simple columnar
�Anatomy, Function, and Evaluation Chapter 1
epithelium .Theseductsareinvolvedwiththereabsorp-tionofsodiumfromtheprimarysecretionandthecon-comitant secretion of potassium into the product . Theabundantpresenceofmitochondria isnecessaryfortheducts’ transportofbothwaterandelectrolytes .Theaci-nus, intercalated duct, and striated duct are collectivelyknownasasinglesecretoryunitcalledasalivon [15] .
Thenextsegmentoftheductsystemismarkedbytheappearanceoftheinterlobularexcretoryductswithintheconnective tissueof theglandular septae .Theepitheliallining is comprised of sparse goblet cells interspersedamongthepseudostratifiedcolumnarcells .Asthediam-eteroftheductincreases,thecompositionoftheepithe-lialliningtransitionstostratifiedcolumnar,andthentononkeratinizedstratifiedsquamouscells,withintheoralcavity[16] .
Thearterialbloodflowreceivedbythesalivaryglandsis high relative to their weight and is opposite the flowofsalivawithintheductsystem .Theaciniandductulesaresuppliedbyseparateparallelcapillarybeds .Thehighpermeability of these vessels permits rapid transfer ofmolecules across their basement membranes . The highvolumeofsalivaproducedbythesalivaryglandsrelativetotheirweightispartlyduetothehighbloodflowratethroughtheglandulartissue .
The serous acini that make up the parotid gland areroughlyspherical,andtheyarecomprisedofpyramidalepithelialcellssurroundedbyadistinctbasementmem-brane .Merocrinesecretionbytheepithelialcellsreleasesa secretory mixture containing amylase, lysozyme, anIgA secretory piece, and lactoferrin into the central lu-menoftheacinus .ThemainexcretoryductisalsoknownasStensen’s ductandemptiesintotheoralcavityoppositetheseconduppermolartooth .
Like the submandibular gland, the sublingual glandhas mixed acini with observable serous demiluneswithin the glandular tissue . Unlike the submandibulargland, however, the sublingual gland is predominantly
Fig. 1.4:Functionalhistologyofthesalivon
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mucinous .Themainductemptiesintothesubmandib-ularductandisalsoknownasBartholin’s duct .Severalsmaller ducts (of Rivinus) also directly secrete into thefloorofthemouth .
The minor salivary glands are found throughout theoralcavity,withthegreatestdensityinthebuccalandla-bialmucosa,theposteriorhardpalate,andtonguebase .Theyarenotasoftenobserved,however,intheattachedgingivaandcloselyassociatedanteriorhardpalatalmu-cosa .Themajorityoftheseglandsareeithermucinousorseromucinous,exceptfortheserousEbner’s glandsontheposterioraspectofthetongue .Thesedeepposteriorsali-varyglandsofthetonguearealsomarkedbythepresenceofciliatedcells, especiallywithin thedistal segmentsoftheexcretoryducts .Theminorsalivaryglandductsystemissimpler thanthatof themajorsalivaryglands,wheretheintercalatedductsarelongerandthestriatedductsareeitherlessdevelopedornotpresent[15] .
Physiology of Salivary Glands
Saliva production, the main function of the salivaryglands, is crucial in the processes of digestion, lubrica-tion, and protection in the body . Saliva is actively pro-ducedinhighvolumesrelativetothemassofthesalivaryglands,anditisalmostcompletelycontrolledextrinsicallybyboththeparasympatheticandsympatheticdivisionsoftheautonomicnervoussystem .
Salivaplaysacrucialroleinthedigestionofcarbohy-dratesandfatsthroughtwomainenzymes .Ptyalinisanα-amylaseinsalivathatcleavestheinternalα-1,4-glyco-sidicbondsofstarchestoyieldmaltose,maltotriose,andα-limitdextrins .ThisenzymefunctionsatanoptimalpHof 7, but rapidly denatures when exposed to a pH lessthan4,suchaswhenincontactwiththeacidicsecretionsofthestomach .Upto75%ofthecarbohydratecontentinameal,however, isbrokendownbytheenzymewithinthestomach .Thisisduetothefactthatasignificantpor-tionofaningestedmealremainsunmixedwithintheoralregion,andthusthereisadelayinthemixtureofgastricjuiceswiththefoodbolus .Starchdigestionisnotslowedin the absence of ptyalin because pancreatic amylase isidentical to salivary amylase and is thus able to breakdownallcarbohydrateswheninthesmallintestine .Thesalivaryglandsofthetongueproducelingual lipase,whichfunctionstobreakdowntriglycerides .Unlikeptyalin,thisenzymeisfunctionalwithintheacidicstomachandprox-imalduodenumbecauseitisoptimallyactiveatalowpH .
Themucusconstituentofsalivafacilitatesthelubrica-tion of food particles during the act of chewing, whichservestomixthefoodwithsaliva .Lubricationeasestheprocessesofswallowingandofthebolustravelingdownthe esophagus . Salivary lubrication is also crucial forspeech .
The antibacterial properties of saliva are due to itsmany protective organic constituents . The binding gly-coprotein for immunoglobulinA (IgA), known as thesecretory piece,formsacomplexwithIgAthatisimmu-nologicallyactiveagainstvirusesandbacteria .Lysozymecauses bacterial agglutination and autolysin activationto degrade bacterial cell walls . Lactoferrin inhibits thegrowthofbacteria thatneed ironbychelatingwith theelement .Salivaalsoservesasaprotectivebuffer for themouthbydilutingharmfulsubstancesandloweringthetemperatureof solutions thatare toohot . Itwashesoutfoul-tasting substances from themouthandneutralizesgastricjuicetoprotecttheoralcavityandesophagus .Xe-rostomia,ordrymouth,duetolackofsalivation,canleadtochronicbuccalmucosalinfectionsordentalcaries .
Comprisedofbothinorganicandorganiccompounds,saliva is distinguished by its high volume compared tosalivaryglandweight,highpotassiumconcentration,andlow osmolarity (Fig .1 .5) . The large relative volume ofsalivaproductionisduetoitshighsecretionrate,whichcangoupto1mlpergramofsalivaryglandperminute .Saliva ismostlyhypotonic toplasma,but itsosmolarityincreaseswithincreasingrateofsecretion,andatitshigh-estratesalivaapproaches isotonicity .Theconcentrationofelectrolytesinsalivaalsochangeswithvaryingsecre-tionrates .
Initially within the salivon, the acini first produce aprimary secretion that is relatively isotonic to plasma .As the saliva travels through theducts,Na+andCl−are
11Anatomy, Function, and Evaluation Chapter 1
reabsorbed, while K+ and HCO3− are secreted into thefluid . Less time is available for the movement of theseelectrolyteswhentheflowrateofsalivaishigher .Athighflowrates,therefore,plasmaandsalivaaresimilarincon-centration .At lowersecretionrates,K+concentrationishigher in the saliva, while Na+ and Cl− concentrationsaresignificantlylower .Bicarbonateconcentratesremainsfairlyhypertonic relative to inplasmaevenwithhigherflowratesdue to its secretory stimulationbymost sali-varyglandagonists .SalivaismostlyhypotonictoplasmaduetothefactthatreabsorptionofNa+andCl−isgreaterthan the secretionofK+andHCO3−within the salivaryducts .
Severalorganiccompoundspresentinsalivahaveal-ready been discussed: α-amylase, lingual lipase, mucus,lysozymes,glycoproteins,lactoferrin,andtheIgAsecre-torypiece .Salivaisalsocomprisedoftheorganicblood group antigensA,B,AB,andO .Kallikreinissecretedbythe salivary glands during increased metabolic activity .
Kallikrein enzymatically converts plasma protein intobradykinin,avasodilator,inordertoincreasebloodflowtotheglands .Salivacontainsapproximatelyonetenththetotalamountofproteinasthatfoundinplasma .
Thesecretion,bloodflow,andgrowthofsalivaryglandsaremostlycontrolledbybothbranchesoftheautonomicnervous system . Even though the parasympathetic ner-voussystemhasmoreinfluenceonthesecretionrateofthe salivary glands than the sympathetic system, secre-tionisstimulatedbybothbranches .
Parasympathetic innervation of the major salivaryglands followsbranchesof the facialandglossopharyn-geal nerves . Parasympathetic stimulation activates bothacinar activity and ductal transport mechanisms, lead-ingtoglandularvasodilationaswellasmyoepithelialcellcontraction .Acetylcholine(ACh)servesastheparasym-patheticneurotransmitterthatactsonthemuscarinicre-ceptorsofthesalivaryglands .ThesubsequentformationofinositoltrisphosphateleadstoincreasedCa2+concen-
trationswithinthecell,releasedfromeitherintracellularCa2+ stores or from the plasma . This second messengersignificantly effects salivary volume secretion . Glandu-lar secretion is sustained byacetylcholinesterases, whichinhibit the breakdown of ACh . The muscarinic antago-nistatropine,however,decreasessalivationbycompetingwithAChforthesalivaryreceptorsite .
Thesympatheticsupplytothesalivaryglandismainlyfromthe thoracic spinalnervesof the superiorcervicalganglion .Likeparasympatheticinnervation,myoepithe-lial cell contractionalso results .Changes inbloodflow,however,arebiphasic:vasoconstrictiondue toα-adren-ergicreceptoractivationisfollowedbyvasodilationdueto buildup of vasodilator metabolites . Binding of theneurotransmitter norepinephrine to α-adrenergic recep-tor results in formationof3',5'-cyclic adenosinemono-phosphate(cAMP),whichthenleadstophosphorylationofvariousproteinsandactivationofdifferent enzymes .Increases in cAMP result in increased salivary enzymeandmucuscontent .
Within saliva, K+ concentrations increase while Na+concentrations decrease in the presence of antidiuretichormone (ADH) or aldosterone . Unlike other digestiveglands,however,thesetwohormonesdonotaffectsali-varyglandsecretionrate .
About1lofsalivaissecretedbyanormaladulteachday .Duringunstimulatedsalivation,69%ofsalivaiscon-tributedbythesubmandibularglands,26%bytheparotid,and 5% by the sublingual glands . The relative amountssuppliedbytheparotidandsubmandibularglands,how-ever,are switchedduringstimulation,where two thirdsofsecretionisthenfromtheparotidgland .Oftotalflow,7–8% is due to the minor salivary glands regardless ofstimulation .Thepresenceoffoodinthemouth,theactofchewing,andnauseaallstimulatesalivation,whilesleep,fatigue,dehydration,andfearinhibitit .Salivarysecretionrates are not dependent on age, and flow rates remainconstantdespite thedegenerationofacinarcellsduringtheagingprocess .Medicationsideeffectsorsystemicdis-easearemorelikelytoberesponsibleforhypofunctionofsalivaryglandsinelderlypatients[15,17] .
theprevalenceofmoderntechnologyintheidentificationof salivaryglanddisorders,adetailedhistoryand thor-ough physical examination still play significant roles intheclinicaldiagnosisofthepatient,andgreatcareshouldbetakenduringtheseinitialstepsofevaluation .
History
When taking a patient’s history, the practiced skills ofattentive listening and patience are required for subse-quentdiagnosisandpropertreatmentmostfittingtothepatient’s expectationsandneeds .Themedicalprofileofthepatientcanprovidehelpfulcluestothecurrentcondi-tionofthesalivaryglands,fordysfunctionoftheseglandsisoftenassociatedwithcertainsystemicdisorderssuchasdiabetesmellitus,arteriosclerosis,hormonalimbalances,andneurologicdisorders .Eitherxerostomiaorsialorrhea,forinstance,maybeduetofactorsaffectingthemedul-larysalivarycenter,autonomicoutflowpathway,salivaryglandfunctionitself,orfluidandelectrolytebalance .
Thefactorsofagegroupandgenderarealso impor-tant,forseveraldiseasesareoftenrelatedtoageorgender .TheautoimmunedisorderknownasSjögren’s syndrome,for example, is common in menopausal women, whilemumps, parotid swelling due to paramyxoviral infec-tion,usuallyoccursinchildrenbetweentheagesof4and10years .
Thesuperficiallocationofthesalivaryglandsallowsthor-ough inspection and palpation for a complete physicalexamination . Initial inspection involves the careful ex-aminationoftheheadandneckregions,bothintraorally
During the initial extraoral inspection, the patientshouldstandthreetofourfeetawayanddirectlyfacingin front of the examiner . The examiner should inspectsymmetry,color,possiblepulsationanddischargingofsi-nusesonbothsidesofthepatient .Enlargementofmajororminorsalivaryglands,mostcommonlytheparotidorsubmandibular,mayoccurononeorbothsides .Parotitistypicallypresentsaspreauricularswelling,butmaynotbevisibleifdeepintheparotidtailorwithinthesubstanceofthegland .Submandibularswellingpresentsjustmedialandinferiortotheangleofthemandible .Salivaryglandswellingcangenerallybedifferentiatedfromthoseoflym-phaticoriginasbeingsingle,larger,andsmoother,butthetwotypesareofteneasilyconfused .Significantneurologicdeficitsshouldbeexaminedaswell .Facialnerveparalysisinconjunctionwithaparotidmass,forexample,shouldremindusofamalignantparotidneoplasm,althoughitdoesoccurrarelywithbenignneoplasmsaswell .
Inadditiontosignsofpossibleasymmetry,discolor-ation,orpulsation,intraoral inspectionalsoincludesas-sessment of the duct orifices and possible obstructions .The proper lighting with a headlight should always beusedwheninspectingwithintheoralcavityandpharynx .TheopeningsofStensen’sandWharton’sductscanbein-spectedintraorallyoppositetheseconduppermolarandattherootofthetongue,respectively .Dryingoffthemu-cosaaroundtheductswithanairblowerandthenpress-ingonthecorrespondingglandswillallowtheexaminertoassess theflowor lackofflowof saliva .Sialolithiasiscan sometimes be found by careful intraoral palpation .Dentalhygieneand thepresenceofperiodontaldiseaseshouldalsobenotedsincedeficientoralmaintenanceisamajorpredisposingfactortovariousinfectiousdiseases .
Size, consistency, and other qualities of the salivaryglandsandassociatedmasses canbeevaluated throughextraoral and intraoral palpation . Bimanual assessmentshouldbeperformedwheneverpossiblewiththepalmaraspectofthefingertips .
Duringextraoral palpation of the face and neck, thepatient’sheadisinclinedforwardtomaximallyexposetheparotidandsubmandibularglandregions .Theexaminermaystandinfrontoforbehindthepatient .Itshouldbenotedthatobservablesalivaryorlymphaticglandswell-ingsdonotrisewithswallowing,whileswellingsassoci-atedwiththethyroidglandandlarynxdoelevate .
Finally,bimanualpalpation(extraoralwithonehand,introral with the other) must be performed to exam-
ine the parotid and submandibular glands . One or twoglovedfingers shouldbe insertedwithin theoral cavitytopalpatetheglandsandmainexcretoryductsinternally,whileusingtheotherhandtoexternallysupporttheheadandneck .Byrollingthehandsovertheglandsbothinter-nallyandexternally,subtlemasslesionscanbeidentified .Inthesubmandibulargland,lymphnodesextrinsictotheglandcanoftenbedistinguishedfrompathologywithinthe gland itself using this technique . The neck shouldthenalsobecarefullyexaminedforlymphadenopathy .
Finally, a careful survey of minor salivary gland tis-sueshouldbeperformed,especiallyintheanteriorlabial,buccal,andposteriorpalatalmucosa .Increasedsalivationfromtheductorificesduetopressureexternallyappliedtotheglandsmayindicateinflammation[9,18] .Finally,rareclinicalentities,suchashemangiomasandothervas-cularanomalies,maybeidentifiedbyauscultation .
Radiologic and Endoscopic Examination of the Salivary Glands
Althoughathoroughhistoryandcompletephysicalex-amination are crucial steps in the diagnosis and even-tual treatment of any salivary gland disorder, patientsoccasionally provide little more than vague complaintsofpainand/orswelling .Forpatientswiththeseunclearsymptomsandnophysicalsigns,radiographicdiagnosticstudies,suchassialography,plain-filmradiography,com-putedtomography,andmagneticresonanceimaging,canplay in importantrole inclarifyingtheetiologyofsuchnonspecificsymptoms .Forpatientswithknowndisease,imagingcanassist in treatment selectionandplanning .This final section will provide a brief introduction tothesevarioustechniques,whichwill thenbecoveredingreaterdetailinsubsequentchapters .
Sialographyreliesontheinjectionofcontrastmediumintoglandularductssothatthepathwayofsalivaryflowcanbevisualizedbyplain-filmradiographs .Correctex-posureandpositioningisachievedbytakingpreliminaryplainradiographspriortotheinjectionofaradiopaquemedium[9] .Themostcommonindicationforsialogra-phyisthepresenceofasalivarycalculus,whichisade-posit of mostly calcium salts that can block flow of sa-livaandcausepain, swelling,and inflammationor leadto infection .Patientswithcalculiusuallycomplainofarecurrent and acute onset of pain and swelling duringeating .Often,sialographicexaminationisunnecessaryifthe preliminary radiographs detect the calculus before-
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hand .Otherindicationsforsialographyincludegradualorchronicglandularenlargement(whichcanbeduetosarcoidosis, infection, sialosis, Sjögren’s syndrome, be-nignlymphoepitheliallesion,oraneoplasm),aclinicallypalpablemass inoneof theglandular regions (possibletumor,cyst,orfocalinflammation),recurrentsialadeni-tis,ordrynessofthemouth .
Although conventional sialography can be clinicallyuseful in the diagnosis and the determination of treat-ment for various salivary disorders, its effectiveness re-mainsarguablewhile itsrateofusage ishighlyvariable[25,30] .Thismethodshouldnotbeperformedwhenthepatienthasanacutesalivaryglandinfection,hasaknownsensitivity to iodine-containing compounds, or is an-ticipatingthyroidfunctiontests .Thus,othermethodsofradiographicdiagnosisarecurrentlypreferredandhavelargelyreplacedsialographicexamination .
Computedtomography(CT)isnowmorewidelyusedtoassesstheparotidandsubmandibularglands .Thead-vantageofCTimagingisthetwo-dimensionalviewofthesalivaryglands,whichcanelucidaterelationshipstoadja-centvitalstructuresaswellastoassessthedrainingcervi-callymphatics .TheparotidglandhaslowattenuationduetoitshighfatcontentandisthereforeeasilydiscerniblebyCTscanning .Thesubmandibularglandhasalowerfatcontentandhigherdensitycomparedtotheparotidglandandthushasamuchhigherattenuation,althoughextrin-sicandintrinsicmassdifferentiationiseasiertoevaluate .Althoughstonescanbeidentified,salivaryglandinflam-mationisnotgenerallyanindicationforCT .WhileCTisoftenutilizedasaprimaryscreeningtoolforthedetec-tionofparotidandsubmandibularglandabnormalities,indifficultcases,ahigher-sensitivityapproachusingbothCTandsialography (CT-sialography)canbeused [24] .Differencesbetweenintrinsicandextrinsicparotidglandmasses, however, are often difficult to assess especiallywhenpresentintheparapharyngealspace[27] .
Magneticresonanceimaging(MRI)ismoreoftenusedfor assessment of parapharyngeal space abnormalities .MRIprovidesbettercontrast resolution,exposes thepa-tienttolessharmfulradiation,andyieldsdetailedimagesonseveraldifferentplaneswithoutpatientrepositioning .Thistechniquethereforeispreferredintheevaluationofparapharyngealspacemasses,especiallyindiscriminatingbetween deep lobe parotid tumors and other pathology,suchasschwannomaand/orglomusvagale .MRI,however,isinferiortoCTscanningforthedetectionofcalcificationsandearlyboneerosion .Chronicinflammationofthesali-varyglandsandcalculiarenotindicationsforMRI .
Sialendoscopyisaminimallyinvasivetechniquethatinspectsthesalivaryglandsusingnarrow-diameter,rigidfiberoptic endoscopes [20] . Endoscopic visualization ofductalandglandularpathologyprovidesanexcellental-ternativetotheindirectdiagnostictechniquesdescribedabove .Assuch,sialendoscopyhasopenedupanewfron-tier forbothevaluationandtreatmentof salivaryglanddisease[21] .Lacrimalprobesareusedtogentlydilatetheductalorificeandthentheendoscopeisintroducedun-der direct visualization . During lavage of the glandularductofinterest,directinspectionoftheductandhilumoftheglandisperformed .Thus,inonesetting,atthetimeofdiagnosis, treatmentandtherapyforbenignlesionscanbe performed (see Chapter6, Sialendoscopy) . Througha CO2-laser papillotomy, sialolithectomy can be easilyperformed[21] .Pharmacotherapyandlaser-ablationcanalsobeperformed .Sialendoscopyhasalsobeenshowntohavea significantly lowcomplicationrateand isgener-allywell-tolerated[31] .Thisrelativelynewtechniquehasshownmuchpromiseinthediagnosisandtreatmentofchronicobstructivesialadenitis(COS),sialolithiasis,andotherobstructivediseasesofthesalivaryglands .
Take Home Messages
→ Salivary gland development is the result ofbranching morphogenesis . Molecular biologyis beginning to unravel signaling pathways im-plicated in both craniofacial development andsalivary gland histogenesis, including the sonichedgehog(Shh)andthefibroblastgrowthfactorfamily .
5 . Davis RA, Anson BJ, Budinger JM, et al . (1956) Surgicalanatomyofthefacialnerveandparotidglandbaseduponastudyof350cervicofacialhalves .SurgGynecolObstet102:385–412
12 . Jaskoll T, Melnick M (1999) Submandibular gland mor-phogenesis: stage-specific expression of TGF-alpha/EGF,IGF,TGF-beta,TNF,andIL-6signaltransductioninnor-mal embryonic mice and the phenotypic effects of TGF-beta2, TGF-beta3, and EGF-r null mutations . Anat Rec256:252–268
20 . Nahlieli O, Baruchin AM (1997) Sialoendoscopy: threeyears’experienceasadiagnosticandtreatmentmodality .JOralMaxillofacSurg55:912–918;discussion919–920
21 . Nahlieli O, Baruchin AM (2000) Long-term experiencewithendoscopicdiagnosisandtreatmentofsalivaryglandinflammatorydiseases .Laryngoscope110:988–993
27 . Som PM, Biller HF (1979) The combined computerizedtomography-sialogram . A technique to differentiate deeplobeparotidtumorsfromextraparotidpharyngomaxillaryspacetumors .AnnOtolRhinolLaryngol88:590–595