11/18/2016 PancoastSyndrome:Background,Pathophysiology,Etiology

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PancoastSyndrome
Updated:Mar28,2014
Author:KarlJD'Silva,MDChiefEditor:JulesEHarris,MD,FACP,FRCPCmore...

OVERVIEW

Background
Pancoastsyndrome(Pancoastssyndrome)ischaracterizedbyamalignantneoplasmofthesuperior
sulcusofthelung(lungcancer)withdestructivelesionsofthethoracicinletandinvolvementofthe
brachialplexusandcervicalsympatheticnerves(stellateganglion).[1,2,3]Thisisaccompaniedbythe
following:

Severepainintheshoulderregionradiatingtowardtheaxillaandscapulaalongtheulnaraspect
ofthemusclesofthehand
Atrophyofhandandarmmuscles
Hornersyndrome(ptosis,miosis,hemianhidrosis,enophthalmos)
Compressionofthebloodvesselswithedema

MostPancoasttumorsaresquamouscellcarcinomas(SCCs)oradenocarcinomasonly35%are
smallcellcarcinomas.Squamouscellcarcinomaoccursmorefrequently,althoughlargecelland
undifferentiatedtypesarealsocommon.Adenocarcinomaissometimesfoundinthislocationandcan
evenbemetastatic.Involvementofthephrenicorrecurrentlaryngealnerveorsuperiorvenacava
obstructionisnotrepresentativeoftheclassicPancoasttumor.

Carefulassessmentandappropriatestagingareperformedbeforesurgery,andselectedpatientsare
administeredpreoperativeirradiationof30Gyover2weeks.Afteranintervalof24weeks,surgical
resectionofthechestwallandlowerbrachialplexusandenbloclungresectionproducesa5year
survivalrateof30%.Contraindicationstosurgicalmanagementincludethefollowing:

Extensionofthetumorintotheneckorvertebrae
Presenceofsubstantialmediastinallymphnodes
Peripheraltumordissemination

Protocolsthatusecombinationsofirradiation,chemotherapy,andsurgeryarecurrentlybeingstudied
todeterminethebesttherapy.

Pathophysiology
Pancoasttumorsareasubsetoflungcancersthatinvadetheapicalchestwall.Becauseoftheir
locationinthepleuralapex,theyinvadeadjoiningtissue.Althoughothertumorsmayhaveasimilar
clinicalpresentationbecauseoftheirlocationatthethoracicinlet,themostcommoncauseisbelieved
tobeabronchogeniccarcinomaarisinginornearthesuperiorsulcusandinvadingadjacent
extrathoracicstructuresbydirectextension.Location,ratherthanpathologyorhistologyoforigin,is
significantinproducingthetumorscharacteristicclinicalpattern.[4]

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11/18/2016 PancoastSyndrome:Background,Pathophysiology,Etiology

ThebulkofatruePancoasttumorisextrathoracic,originatinginanextremeperipherallocationwitha
plaquelikeextensionoverthelungapexandprincipallyinvolvingthechestwallstructuresratherthan
theunderlyinglungparenchyma.Bronchogeniccarcinomasoccurringinthenarrowconfinesofthe
thoracicinletinvadethelymphaticvesselsintheendothoracicfasciaandinclude,bydirectextension,
theintercostalnerves,thelowerrootsofthebrachialplexus,thestellateganglion,thesympathetic
chain,andadjacentribsandvertebrae.

CarcinomasinthesuperiorpulmonarysulcusproducePancoastsyndrome,thuscausingpaininthe
shoulderandalongtheulnarnervedistributionofthearmandhand.[5](Thesecarcinomasalsocause
Hornersyndrome.)Theseapicallungtumorstendtobelocallyinvasiveearly.Intheabsenceof
metastasesandregionalnodalinvolvement,theseapicalcancerscanbesuccessfullytreated.

Thetumormayinvadethebonystructuresofthechest.Thefirstorsecondthoracicvertebraorthe
first,second,orthirdribsmaybeinvaded.Inareviewof60patientswithPancoasttumors,Maggiet
alfoundradiographicevidenceofriberosionin50%analmostequalpercentagedemonstrated
involvementofthefirstorsecondrib,and20%hadinvolvementofthethirdrib.Onepatienthad
involvementofall3ribs.[6]

Thetumorcanalsoinvadethefirstorsecondthoracicvertebralbodiesorintervertebralforamina.
Fromthispoint,itcanextendtothespinalcordandresultincordcompression.Thesubclavianvein
orarterymayalsobeinvaded.

Etiology
TheoverwhelmingmajorityofcasesofPancoastsyndromearenonsmallcelllungcarcinoma
(NSCLC),withmorethan95%locatedinthesuperiorsulcus.ThemostcommonvarietiesareSCC
andadenocarcinomalargecellcarcinomahasalsobeenreported.

Althoughquiterare(responsibleforfewerthan5%percentofcasesinmostseries),smallcell
carcinomaisalsoobserved.Maggietalreportedonly3patientswithsmallcellcarcinomaintheir
1994seriesof60patients.[6]Moretypically,smallcellcarcinomamanifestsinacentralratherthana
peripherallocation.

AlthoughNSCLCisbyfarthemostcommoncauseofPancoastsyndrome,thelistofdifferential
diagnosesisbroad.BecauseofthewidevarietyofdiseasesthatcanproducePancoastsyndrome,a
histologicdiagnosisismandatorybeforedefinitivetreatmentisinitiated.

Inrareinstances,benigntumorssuchasdesmoidtumors(caserecordsoftheMassachusetts
GeneralHospital:weeklyclinicopathologicalexercises,2000)orhemangiopericytoma[7]maycause
thecondition.Adenoidcysticcarcinoma,[8]metastaticcarcinoma,[9]lymphoma,[10]andthyroid
carcinoma[11]haveallbeenassociatedwiththesyndrome.Infectiousprocesses,includingbacterial
[12,13] andfungalinfections[14,15] mayalsobeinvolved.

Othercausesincludelymphomatoidgranulomatosis,vascularaneurysms,amyloidnodules,and
cervicalribsyndrome.Inflammatorypseudotumor(plasmacellgranuloma),mycoticsubclavianartery
aneurysm,andcarotidpseudoaneurysminachild(causedbyahydatidcyst)havebeenreported.

Riskfactorsaresimilarforalmostalllungcancers.Theyincludepriorprolongedasbestosexposure,
exposuretoindustrialelements(eg,gold,nickel),smoking,andsecondarysmokeexposure.

Epidemiology
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11/18/2016 PancoastSyndrome:Background,Pathophysiology,Etiology

Overall,Pancoasttumorsaremuchlesscommonthanotherlungcancers,accountingforfewerthan
5%ofthesecancers(13%invariouspreviousseries).[16,17]Originallydeemeduniversallyfatal,
Pancoasttumorsarenowamenabletocurativetreatmentbecauseofimprovementsincombined
modalitytherapyanddevelopmentofnewtechniquesforresection.

Prognosis
TheprognosisforPancoastsyndromeisstagedependent.Adverseprognosticfactorshavebeen
identifiedandincludethefollowing:

PresenceofHornersyndrome
Involvementofmediastinallymphnodes
Incompleteresection
Involvementofsupraclavicularlymphnode
Vertebralbodyinvasion

Todate,nopatientwiththefirst3prognosticfactorshassurvivedfor5years.

Distantdiseaselimitssurvival.Thebrainisthefrequentsiteoffailureforsuperiorsulcustumors.The
authorsrecommendcarefulsurveillanceforbrainmetastasisduringandafterthetherapy.Theauthors
alsorecommendobtainingbrainimagingpriortosurgeryinpatientsreceivinginductiontherapyforthe
primarytumor.

Mortalityandsurvival
Attaretalreportedamediansurvivalof36.8monthsinpatientswithT3lesionsundergoingcombined
modalitytreatmentmediansurvivalwasonly6.4monthsifthepatienthadT4disease.[18]

OverallsurvivaldataweresummarizedbyDetterbeck,whonotedthat5yearsurvivalratesranged
from15%to56%.[19]Ofthe104patientstreatedbyAttarandcoworkers,7(~7%)were5year
survivorsand3(~3%)were10yearsurvivors.[18]Anotherstudydemonstratedsurgicalmorbidity
ratesof738%,withmortalityrangingfrom5%to10%.[20]

Forneoplasticcauses,predictorsof5yearsurvivalareweightloss,supraclavicularfossaorvertebral
bodyinvolvement,diseasestage,andsurgicaltreatment.AstudybyanMDAndersongroupreported
thefollowingfindings[21]:

ForpatientswithstageIIBdisease,the5yearsurvivalratewas47%,whereasforthosewith
stageIIIAandIIIBdisease,itwas14%and16%,respectively
InpatientswithstageIIBdisease,surgicaltreatmentandweightlossweresignificant
independentpredictorsof5yearsurvival
AmongpatientswithstageIIIAdisease,theonlypredictorofsurvivalwastheKarnofsky
performancescore
InpatientswithstageIIIBdisease,theonlyindependentpredictorofsurvivalwasaright
superiorsulcuslocation,whichwasassociatedwithaworse5yearsurvivalratethanaleft
superiorsulcuslocation
Comparedwithpatientswhohadsquamouscelltumors,morepatientswithadenocarcinoma
hadcerebralmetastaseswithin5years

Relapse

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11/18/2016 PancoastSyndrome:Background,Pathophysiology,Etiology

Locoregionalrelapseiscommondespitepreoperativeorpostoperativeradiationtherapy.Muscolinoet
alfoundlocoregionalrecurrencein60%ofpatientstreatedwithacombinedradiosurgicalapproach.
Ginsbergetalfoundthat94oftheir124patientshadrecurrenceofdisease,with72%ofthesecases
beinglocoregionalatinitialrecurrence.Intwothirdsofpatientswhounderwentcompleteresection,
localrecurrenceswerethefirstsiteofrelapse.[16]

ThisdistributionofrelapseswasnotedinseveralstudiesreviewedbyDetterbeck.Inmanyofthese
studies,patientsreceivedpreoperativeradiationtherapy.[19]IntheMemorialSloanKettering
experience,additionalpostoperativebrachytherapywasadministeredtoachievemaximalpossible
localcontroldespitethesemeasures,localrelapses,and,ultimately,distantrelapses,werefrequent.
[16]

ClinicalPresentation

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MediaGallery

of0

Tables

Table.AJCC/UICCStagesforPancoastTumors.

Table.AJCC/UICCStagesforPancoastTumors.

Stage T(Tumor) N(Nodes)

IIB T3 N0

T3 N1
IIIA
T3 N2

AnyT N3
IIIB
T4 AnyN

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ContributorInformationandDisclosures

Author

KarlJD'Silva,MDAssistantClinicalProfessorofMedicine,DepartmentofHematology/Oncology,
LaheyClinic,SophiaGordonCancerCenter

KarlJD'Silva,MDisamemberofthefollowingmedicalsocieties:MassachusettsMedicalSociety

Disclosure:Nothingtodisclose.

Coauthor(s)

SarahKMay,MDConsultingStaff,DepartmentofHematologyOncology,CaritasCarneyHospital,
CommonwealthHematologyOncologyPC
http://emedicine.medscape.com/article/284011overview 7/10
11/18/2016 PancoastSyndrome:Background,Pathophysiology,Etiology

Disclosure:Nothingtodisclose.

ChiefEditor

JulesEHarris,MD,FACP,FRCPCClinicalProfessorofMedicine,SectionofHematology/Oncology,
UniversityofArizonaCollegeofMedicine,ArizonaCancerCenter

JulesEHarris,MD,FACP,FRCPCisamemberofthefollowingmedicalsocieties:American
AssociationfortheAdvancementofScience,AmericanSocietyofHematology,CentralSocietyfor
ClinicalandTranslationalResearch,AmericanSocietyofClinicalOncology

Disclosure:Nothingtodisclose.

Acknowledgements

ShabirBhimji,MD,PhDLocumCardiothoracicandVascularSurgeon,SaudiArabiaandMiddleEast
Hospitals

ShabirBhimji,MD,PhDisamemberofthefollowingmedicalsocieties:AmericanCancerSociety,
AmericanCollegeofChestPhysicians,AmericanLungAssociation,andTexasMedicalAssociation

Disclosure:Nothingtodisclose.

ShreekanthVKarwande,MBBSChair,Professor,DepartmentofSurgery,DivisionofCardiothoracic
Surgery,UniversityofUtahSchoolofMedicineandMedicalCenter

ShreekanthVKarwande,MBBSisamemberofthefollowingmedicalsocieties:AmericanAssociation
forThoracicSurgery,AmericanCollegeofChestPhysicians,AmericanCollegeofSurgeons,
AmericanHeartAssociation,SocietyofCriticalCareMedicine,SocietyofThoracicSurgeons,and
WesternThoracicSurgicalAssociation

Disclosure:Nothingtodisclose.

JeffreyCMilliken,MDChief,DivisionofCardiothoracicSurgery,UniversityofCaliforniaatIrvine
MedicalCenterClinicalProfessor,DepartmentofSurgery,UniversityofCalifornia,Irvine,Schoolof
Medicine

JeffreyCMilliken,MDisamemberofthefollowingmedicalsocieties:AlphaOmegaAlpha,American
AssociationforThoracicSurgery,AmericanCollegeofCardiology,AmericanCollegeofChest
Physicians,AmericanCollegeofSurgeons,AmericanHeartAssociation,AmericanSocietyfor
ArtificialInternalOrgans,CaliforniaMedicalAssociation,InternationalSocietyforHeartandLung
Transplantation,PhiBetaKappa,SocietyofThoracicSurgeons,SouthwestOncologyGroup,and
WesternSurgicalAssociation

Disclosure:Nothingtodisclose.

MichaelPerry,MD,MS,MACPNellieBSmithChairofOncologyEmeritus,Director,Divisionof
HematologyandMedicalOncology,DeputyDirector,EllisFischelCancerCenter,Universityof
MissouriColumbiaSchoolofMedicine

MichaelPerry,MD,MS,MACPisamemberofthefollowingmedicalsocieties:AlphaOmegaAlpha,
AmericanAssociationforCancerResearch,AmericanCollegeofPhysicians,AmericanCollegeof
PhysiciansAmericanSocietyofInternalMedicine,AmericanMedicalAssociation,AmericanSociety

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11/18/2016 PancoastSyndrome:Background,Pathophysiology,Etiology

ofClinicalOncology,AmericanSocietyofHematology,InternationalAssociationfortheStudyofLung
Cancer,andMissouriStateMedicalAssociation

Disclosure:Nothingtodisclose.

FranciscoTalavera,PharmD,PhDAdjunctAssistantProfessor,UniversityofNebraskaMedical
CenterCollegeofPharmacyEditorinChief,MedscapeDrugReference

Disclosure:MedscapeSalaryEmployment

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