Extracranial neurogenic tumors of the head and neck,

www.bjorl.org

Brazilian

Journal

of

OTORHINOLARYNGOLOGY

ORIGINAL

ARTICLE

Extracranial

neurogenic

tumors

of

the

head

and

neck

夽,夽夽

Otávio

Alberto

Curioni

_,

_Ricardo

_Pires

_de

_Souza

_,

Ana

Maria

da

Cunha

Mercante

,

Ana

Carolina

de

Jesus

,

Alysson

Pavelegeni

_,

_Rogério

_Aparecido

_Dedivitis

_,

_Abrão

_Rapoport

f_{LarynxGroup,DepartmentofHeadandNeckSurgery,HospitaldasClínicas,FaculdadedeMedicina,UniversidadedeSãoPaulo}

(USP),SãoPaulo,SP,Brazil

g_{DepartmentofSurgery,FaculdadedeMedicina,UniversidadedeSãoPaulo(USP),SãoPaulo,SP,Brazil} h_{DepartmentofHealth,HospitalHeliópolis,SãoPaulo,SP,Brazil}

i_{HospitalSãoJosédaRBBP,SãoPaulo,SP,Brazil}

Received21April2014;accepted8October2014 Availableonline8September2015

KEYWORDS

Neurilemmoma; Neurofibromatosis; Neurofibromatoses; Neurofibrosarcoma; Headandneck neoplasms

Abstract

Introduction:Periphericnervetumors typicallyderivefromSchwanncellsoftheperipheral nervesheet.Sincethese tumorsareuncommon, they shouldbeconsideredinpreoperative differentialdiagnosis.

Objective:Toreporttheexperienceofatertiarycaredepartment.

Methods:Forty-twopatientswithheadandneckperipheralneurogenictumorswere retrospec-tivelyanalyzedandevaluatedfrom1977to2013.Thepreoperativediagnosiswasconfirmedby biopsyorimagingstudy.

Results:Themeanagewas41.7and15patients(36%)weremale.Themeansizewas5.5cmand 26(61%)werelocatedlaterallyintheneck.Mosttumors(39.9%)presentedasanasymptomatic neckmass. Most (39.9%) were resected througha neckapproach. Cranial nerves were the commonestsiteoforigin.

夽 _{Pleasecitethisarticleas:CurioniOA,deSouzaRP,MercanteAMC,deJesusAC,PavelegeniA,DedivitisRA,etal.Extracranialneurogenic}

tumorsoftheheadandneck.BrazJOtorhinolaryngol.2015;81:604---9.

夽夽_{Institution:DepartmentofHeadandNeckSurgeryandOtorhinolaryngology,HospitalHeliópolis,SãoPaulo,SP,Brazil.} ∗_{Correspondingauthor.}

E-mail:dedivitis@usp.br(R.A.Dedivitis).

http://dx.doi.org/10.1016/j.bjorl.2015.08.012

1808-8694/©2015Associac¸ãoBrasileiradeOtorrinolaringologia eCirurgiaCérvico-Facial. PublishedbyElsevierEditoraLtda.All rights reserved.

Conclusions: Extracranial neurogenic tumors presented with a mean size of 5.5cm, were locatedlaterallyintheneck,normallyhadtheiroriginfromcranialnerves,andtheirresection approachiscervical.

© 2015Associac¸ãoBrasileira de Otorrinolaringologiae CirurgiaCérvico-Facial. Publishedby ElsevierEditoraLtda.Allrightsreserved.

PALAVRAS-CHAVE

Neurilemoma; Neurofibromatose; Neurofibromatoses; Neurofibrossarcoma; Neoplasiasdecabec¸a epescoc¸o

Tumoresneurogênicosextracranianosnacabec¸aepescoc¸o

Resumo

Introduc¸ão: Tumoresdosnervos periféricostipicamentederivamdascélulas deSchwann da bainhadosnervosperiféricos.Porseremincomuns,devemserlembradosnodiagnóstico dife-rencialpré-operatório.

Objetivo: Relataraexperiênciadeservic¸odereferenciaterciária.

Método: De 1977a 2013, 42 pacientescom tumores neurogênicos periféricos da cabec¸a e pescoc¸o foram operados e analisados retrospectivamente. A confirmac¸ão diagnóstica pré-operatóriadeu-seporbiópsiaoumétododeimagem.

Resultados: Amédiadaidadefoide41,7anos,sendo15indivíduos(36%)dogêneromasculino. Otamanhomédiofoide5,5cme26(61%)localizavam-senafacelateraldopescoc¸o.Amaior parte(39,9%)apresentou-secomotumorpalpávelassintomático.Amaioria(39,9%)foiressecada poracessocervical.Amaioriaoriginou-sedenervoscranianos.

Conclusões: Tumoresneurogênicosextracranianosapresentam-secomtamanhomédiode5,5 cm,nafacelateraldopescoc¸o,costumamoriginar-sedenervoscranianoseserressecadospor viacervical.

©2015Associac¸ãoBrasileiradeOtorrinolaringologiaeCirurgiaCérvico-Facial.Publicado por ElsevierEditoraLtda.Todososdireitosreservados.

Introduction

Tumorsarisingfromperipheralnervestypicallyarederived fromSchwanncellslocatedintheperipheralnervesheath, commonly from cranial nerves, but also from sensory or motor nerves and nerves of the sympathetic nervous sys-tem.Amongthemanynamesusedtodescribethesetumors, twoinparticular---schwannomasandneurofibromas---have significantclinicaldifferencesthatrequirediscussion.Asa group,neurogenictumorsoccurmostcommonlyinthehead andneckin25---45%ofcases.1---3

These tumors are reported in the parapharyngeal and

retropharyngealspace,posteriorpharyngealwall,paranasal

sinuses, nasal cavity, scalp, submandibular region,

lar-ynx, epiglottis, tongue, infratemporal fossa, oral cavity,

etc.4---6_{Often,suchtumorspresentasanasymptomatic}

lat-eral neck mass, although they can cause symptoms such

as nasal obstruction, dysphagia, and dysphonia,

depend-ing on their location and size. Sometimes these tumors

may be associated with other diseases, such as multiple

endocrine neoplasia or neurofibromatosis type 1.

Consid-ering that they are relatively rare, these tumors should

be considered in preoperative differential diagnosis, as

otherprimarynecktumorsmaypresentasanasymptomatic

neck mass; moreover, their resection may require neural

reconstruction,andthesurgeonmustbepreparedfor this

possibility.

The aim of this study was to report the

experi-ence in addressing these tumors by a tertiary referral

service.

Methods

ThisstudywasapprovedunderNo.554bytheEthics

Com-mitteeoftheinstitution.

FromDecemberof1977toDecemberof2013,42patients

withneurogenictumorsoftheheadandneckwith

periph-eraloriginunderwentsurgery.Themedicalrecordsofthese

patientswereretrospectivelyreviewed.Afterhistory

collec-tionandphysicalexamination,thecollectionofmaterialfor

histopathologicaldiagnosiswasperformedwhenever

possi-ble,fordiagnosticpurposes.Thus,intumorsthatcouldbe

accessedatphysicalexaminationorbyendoscopy,suchas

nasalandoralcavitytumors,incisionalbiopsyorpuncture

wasperformed.Fineneedleaspiration(FNA)wasperformed

ontumorslocatedinmoresuperficialportionsoftheneck.

In the case of deep tumors, such as those arising in the

parapharyngealspace(onecase),tissuecollectioncouldnot

beperformed(Table1).Inmanypatients,computed

tomo-graphy(CT)and/ormagneticresonanceimaging(MRI)were

performed(Figs.1---3).

Tumorexcision (with separationof thenerveof origin)

andintracapsularenucleationincasesofschwannoma,and

resection witha safety margin in case of neurofibromas,

wereconducted.Histologicaldiagnosiswasconfirmedwith

thestudyofparaffinblockspecimens(Table2).

Results

At treatment, the mean age was 41.7 years (range

Table1 Anatomicsiteof42headandneckneurogenictumorsanddiagnosismodality.

Location n(%) Diagnosticbyimagingmethod DiagnosticbyFNA Diagnosisbyincisionalbiopsy

Lateral 26(61) 4 16 6 Supraclavicularfossa 7(16) 1 1 5 Submandibular 4(9) 0 1 3 Integument 3(7) 0 1 2 Parotidgland 1(2) 0 1 0 Frontoethmoidalregion 1(2) 1 0 0

FNA,fineneedleaspiration.

Figure1 Valgusnerveschwannoma:axialcomputedtomographyshowsaheterogeneousmasswithwell-definedlimits,displacing theinternalcarotidarteryandinternaljugularvein.

27(64%) female.The meantumor size was5.5cm (range 2.0---15.0cm). Of these tumors, 26 (61%) occurred in the lateralaspectoftheneck(Table1).

Most tumors (39.9%) presented as a palpable

asymp-tomaticmass.Two(5%)patientspresentedwithparesthesia

inupperlimb, andonecase (2%)hadpainandobstructive

symptoms.

Mosttumors (39.9%)were resected by cervical access.

One patientpresented bulging in the hemiface and signs

ofnasalobstruction,andunderwentabiopsyvia

Caldwell-Lucprocedureandsubsequentpartialmaxillectomy.Inboth

Figure2 Mandibularnerveschwannoma:coronal computed tomographyandmagneticresonanceimagingshowa

hourglass-like mass with a localized shaft and widening of the oval

foramen,withintracranialcomponentsandinthe masticator space.

Table2 Histopathologictypes.

Histology n(%)

Schwannoma 20(48)

Neurofibroma 18(43)

Neurofibromatosis 3(7)

Neurosarcoma 1(2)

cases,theresectionwascarriedoutbyintracapsular enucle-ation.Inoneofthecases,referredwithpreviousdiagnosisof lateralcervicalneurofibroma,theCTshowedboneerosions inC4 andC5vertebralbodies,andthepatientunderwent resectionofthelesionwithorigininC4andC5roots, requir-ingresectionofpartsofthevertebralbodyandsubsequent reconstruction.Therewasnorecurrenceinthispatient pop-ulationafterafollow-uprangingfrom24to60months(mean 40months).

Asforthenerveoforigin,mosttumorsoriginatedfrom cranialnerves VII,X, XI,andXII,ten casesstemmedfrom the brachial plexus, followed by cervical plexus, cervical sympathetic,C3toC7roots; andinfivecasestheir origin wasnotidentified(Table3).

Discussion

Embryologically, neurogenic tumors originate from the

neural crest and can be formed from Schwann cells or

synpathoblasts.7_{Theformercellsoriginatefroma}

special-izedpopulationofneuromesenchymalcellsfromtheneural

Figure3 Naso-ethmoidneurofibroma:coronalcomputedtomography withsofttissuewindow,showinganaso-ethmoidalsolid masswithmedialorbitalwallremodeling.

Table3 Tumororigin.

Origin n(%) Brachialplexus 10(24) Cervicalplexus 9(21) Vagusnerve 4(10) C3toC7roots 4(10) Cervicalsympathetic 3(7) Lingualnerve 3(7) Hypoglossalnerve 2(5) Accessorynerve 1(2) Facialnerve 1(2)

Minornerves/notdefined 5(12)

two entities can arise from any cranial nerve or spinal root with a sheath, that is, from any motor or sensory nerve,except theopticand olfactory nerves, whichhave noSchwanncellsheath,astheyaredirectextensionsofthe centralnervoussystem.9

The cell population of schwannomas has an exclusive

originfromSchwanncells,whileneurofibromascomprisea

mixtureofthreecells:Schwanncells,perineuralcells,and

perineuralfibroblasts.8

Inthepresentstudy,themeanageofpatientswas41.7

years,withpredominanceoffemales(27/42);someauthors

agree1 _{with this finding, while others disagree.}10 _{A study}

reportedthatschwannomas canarise atany age,withno

preferenceforageorrace.7

Thesizeofthesetumorscanrangefromafewmillimeters

toover 24cm.7 _{Inthis sample, thevariationwas2---15cm}

withameanof5.5cm.

Ingeneral,theschwannomaisaslow-growing,isolated,

encapsulated tumor, connected with the nerve of origin.

When localized in the head and neck, it affects patients

at any age; however, reports indicate a preponderance

in the fifth decade of life.11 _{Generally, schwannomas}

show degenerative changes such as cystic alterations

and hemorrhagic necrosis; such changes are not seen in

neurofibromas.2 _{If thereisinvolvement of amajornerve,}

theremaybeseveredysfunctionthat,clinically,can

mani-festasvocalfoldparalysis,Hornersyndrome,orsensoryor

motordysfunctionoftheupperlimb,amongothers.Inthe

presentstudy,two(2%)patientshadsensorydisorderofthe

upper limb, one (1%) patient had obstructive symptoms,

and the remaining presented a neck mass; this coincides

withtheliterature.7

According to reports in the literature, the most

com-mon site of extracranial schwannomas in the head and

neckis theparapharyngealregion:in fact,theseare

usu-allyretro-styloid injuries in the carotid space that cause

anteriordisplacementofthefatpresentinthepre-styloid

parapharyngealspace, with bulging of the lateral wall of

oropharynx.12---15 _{Othersites intheheadandneck,suchas}

thesubmandibularregion,paranasalsinuses,face,andoral

cavity,arerare.16_{Asforlocation,casesonthelateralaspect}

oftheneckpredominated,andmostoccurredinthe

para-pharyngealregion.

Most often, neurofibromas affect patients aged 20---30

yearsandhave nopredilectionfor gender.Clinically,

neu-rofibromascanpresentasanisolatedtumororinamultiple

form (disseminated tumors). Most often, localized

neu-rofibromas arise from cutaneous nerves, with occasional

involvement of deep nervous sheath. This is a benign,

slow-growing,relativelycircumscribedbutunencapsulated

tumor.In thefirst case, thereisnoknown cause(60---90%

ofcases),andthesetumorsareknownassolitary

neurofi-broma,withvaryinganatomicdistribution.17_Inabout10%of

cases,thereisanassociationwithneurofibromatosistype1

syndrome,inassociationwithasomaticmutationintheNF1

gene,atumorsuppressorgenelocatedonchromosome17.18

A critical issue regarding the treatment of neurogenic

tumorsoftheheadandneckisthediagnosis,whichisbased

onclinicalfindings,namely,theonsetofalong-standing

incidentallyonimagingstudies. The determination ofthe

nerveoforiginisstrategic,sincethisprovidesthe

possibil-ityofaninformeddecision,bythepatient,aboutanyriskof

post-treatmentfunctionalsequelae.Althoughcytologymay

beofassistance,inmostcasesthetechniqueofaspiration

punctureisinconclusive.19---21

Thespecificityofimagingstudiesisalsonothigh.These

tests lend themselves more to treatment planning and

evaluationofthevascularizationoftumors,whichis

some-times very rich, and are less useful for diagnosis of the

tumor’s nerve of origin, although that is possible in

cer-tain situations.22 _{As for the use of CT and MRI, most}

authors prefer the latter technique.23,24 _{High-resolution}

CT (HRCT) determines the size and extent of the tumor,

demonstrates the degree of tumor vasculature, and

dif-ferentiates between benign and malignant lesions. In CT

and MRI, schwannomas usually present as a spherical or

ovoid soft tissue mass, and can show non-homogeneous

contrast enhancement, a cystic component, and fatty

degeneration.25

Incidenceofmalignantschwannomasandthemalignant

transformationrateofbenign schwannomasarenot

avail-able in the literature. A study on intracranial malignant

peripheral nervesheathtumors suggested sporadic

devel-opment, and no transformation of benign tumors.26 _Most

neurofibromasare single lesionsnot associated with

neu-rofibromatosis;however, when combinedwith NF1, there

is a small risk of malignancy. Based on this

circumstan-tialevidence, in both casesthe malignanttransformation

ratecanbe considered arareevent inpatients with

soli-taryschwannomaandneurofibromaoftheheadandneck.

Becauseofthe indolentnatureandtheremotechance of

malignanttransformation,it is possibletoopt for clinical

follow-up.Therefore,thedecisioninfavorofsurgeryshould

bebasedonananalysisoftherisksandbenefitsofthe

surgi-caltreatment;i.e.,preoperativesymptomaticseverityand

predictedpostoperativeneurologicaldeficit.

Amongthedifferentialdiagnoses,reactiveormetastatic

lymphnode diseases; soft tissue tumors such asfibroma,

leiomyoma, lipoma, and paraganglioma; carotid artery

aneurysm;andbranchialabnormalitiesshouldbeincluded.

The choice between resection of the tumor with

sec-tioningofthenerveof originor intracapsularenucleation

withthepossibilityof preservingnervefunction ismainly

determinedbytherelationshipbetweenthetumorandthe

nerveoforigin.Intracapsularenucleationis morefeasible

ineccentricallylocatedtumors,withoutdispersingthe

neu-ral fibers. Inneurofibromas, the ruleis to performtumor

resectionwithasafetymargin.

In histopathological examination, the classic

schwan-nomarevealsabiphasicpatterncomposedoftwotypesof

cellular patterns: Antoni A and Antoni B. Antoni A areas

arecomposedofspindlecellswithlong,thinfibers,

form-ingnuclear arrangementsin parallel,known aspalisading

nuclei,aroundacentralcytoplasmicmass(Verocaybodies).

AntoniBareas areof degenerativenature.The tissueisa

looselydisposedstroma inwhichneuralfibersandcellsdo

notformanydistinctpattern.Bothtypescanarisetogether.

Variantsofschwannomaweredescribed;cellular,plexiform,

epithelioid,melanotic,andancientformsarethefivemain

variantsofthistumor.Threevariantsofneurofibromahave

alsobeendescribed:localized,plexiform,anddiffuseforms.

The recurrencerates after resectionarenot well

doc-umented in the literature. Recurrence following en bloc

resectionisararefinding.Inthepresentseries,therewasno

recurrenceafterameanfollow-upof40months.Thetumor

isradio-resistant,andradiationtherapyshouldbereserved

forpalliativetreatmentincaseswheresurgeryisimpossible,

howeverimperative.3

Conclusions

The mean age was41.7years; 36%were male. Mean size

was5.5cm;61tumorswerelocalizedinthelateralaspect

of theneck; 39.9%presented asapalpableasymptomatic

mass;39.9%wereresectedthroughcervicalaccessandmost

oftheselesionshadtheirorigininthecranialnerves.

Conflicts

of

interest

Theauthorsdeclarenoconflictsofinterest.

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