Clinical Medical & Case Reports

Open Journal of

ISSN2379-1039

Volume3(2017)Issue25

SchroederJ

OpenJClinMedCaseRep:Volume3(2017)

Glioblastomamultiforme:Anincidental�inding?TarekMansour;LukeMugge;ManishKaramchandani;RobertMrak;KevinReinard;JasonSchroeder*

*JasonSchroeder

DepartmentofSurgery,DepartmentofNeurologicalSurgery,UniversityofToledoMedicalCenter,

3000ArlingtonAve,Toledo,OH43614

Email:Jason.schroeder5@utoledo.edu

Abstract

Incidents of patients diagnosed with concomitant primary glioblastoma multiforme (GBM) and

meningiomalesionsareextremelyrarebuthavebeenreporteddatingbacktothe1970s.Themajorityof

documentedcasesofconcurrentGBMandmeningiomaportraythetumorstobeincloseproximityandin

comparablestagesofdevelopment.Herein,wereportacaseofprimaryGBMandagiantmeningioma

tumors that not onlydeveloped at opposite poles of thebrainparenchyma, butwere also of vastly

different sizes and stages of development upon initial presentation. These differences ultimately

preventedsimultaneousdiagnosisandresectionofthetumors.Uponresection,pathologicalanalysisof

thegianttumorshowedthatitwasindeedameningiomaanddemonstratedevidenceofbraininvasion

andmicrovascularinvolvement.TheotherlesiondemonstratedclassicsignsofGBMonpathologicwork-

up. The case presented highlights the complexity of patients presenting with concomitant neuro-

oncologicdiseaseandtheneedtosystematicallyaddressindividualissuesattheirindividualappropriate

time.

Keywords

glioblastomamultiforme;meningioma;concomitantdevelopment;gliomagenesis;oncogenicsignaling

cascade

Introduction

Concomitantprimaryglioblastomamultiforme(GBM)andmeningioma lesionsareextremely

rare.Initialreportssitetheuseofradiosurgeryforonelesionasthecauseofthedevelopmentoftheother.

Therehavebeenseveralreportsofconcomitantlesiondatingbacktothe1970s[1].Themajorityofthese

documented cases demonstrate the tumors to be in close proximity, in comparable stages of

development, and involving the same anatomical structures. In a report byMaiuriet al. on several

concomitantmeningiomasandotherintracranialtumors,thecloseproximityandpresumablysimilar

stagingofthetumorsallowedforsimultaneousidenti�icationandresectionofbothtumors,oftenviathe

Abbreviations

GBM:GlioblastomaMultiforme;CT:ComputedTomography;MRI:MagneticResonanceImaging;PDGF:

PlateletDerivedGrowthFactor;RTK:ReceptorTyrosineKinase;EGFR:EpidermalGrowthFactor

Receptor;VEGF:VascularEndothelialGrowthFactor

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samesurgicalapproach[2].

Herein,wereportacaseofprimaryGBMandmeningiomatumorsthatnotonlydevelopedat

oppositepolesofthebrainparenchyma,butwerealsoofvastlydifferentsizesandstagesofdevelopment

uponinitialpresentation.Thesedifferencesultimatelypreventedsimultaneousdiagnosisandresection

of the tumors. Clinical manifestations, imaging �indings, possible mechanisms, and impact on

managementarediscussed.

ClinicalSummary

A60-year-oldpatientpresentedtotheemergencydepartmentwithalteredmentalstatusand

featuresof confusionandacuteparanoiawithdelirium. Initial computed tomography (CT) �indings

showedagiantleftfrontalmeningiomaandasmallrightparieto-occipitalhypodenselesion;�indings

thatwerecon�irmedonmagneticresonanceimaging(MRI).Thepatientsubsequentlyunderwentabi-

frontalcraniotomyandcompleteresectionofthemeningiomawasperformed.Thepatient'spresenting

symptomsappearedtoberelatedonly to themeningiomaand itsassociatededema.Becauseof the

urgencyinneedingtoremovethegiantmeningiomafordecompressionofmasseffectandasubsequent

complicatedpost-operativecourse,noimmediatefurtherinvestigationoftheparieto-occipitallesion

wasperformed.

Post-operativerecoverywascomplicatedbyprolongedencephalopathyandrespiratoryfailure.

Thepatient'sstatusrequiredtrachandPEGtubeplacementpriortodischargetoanursinghomefacility

at approximately one month post-op. During recovery in a nursing home, the patient's condition

continuedtodeteriorate.Thisdeteriorationwaspartlyattributedtodysfunctionofhisfeedingtubeand

progressive weight loss associated with malnutrition. During re-admission to the hospital for his

malnutritionthepatienthadfollow-upimagingtoevaluateforpossiblehydrocephalus,cranialinfection

orothercauseofhisprogressiveneurologicaldecline.

On this follow-up imaging the previously small right parieto-occipital lesion had grown

signi�icantlywithexpansionof theassociatedgyri,demonstrationofassociatedcerebraledemaand

progression across the posterior corpus callosum – all of which features were considered

radiographicallytobeconsistentwithGBM.Multipleconversationsensuedwiththepatient's family

regardingthe likelydiagnosisandpotentialoutcomeforhisprogressivebraintumor.Ultimately the

patientwastransitionedtohospicecare.

PathologicalFindings

Pathologicalanalysisofthetumorsshowedthatthegianttumorwasindeedameningiomaand

demonstrated evidence of brain invasion andmicrovascular involvement. Additionally, the parieto-

occipitallesionwascon�irmedtobeaglioblastomamultiformetumorbyvirtueoftheclassicalsignsseen

onthepathologicalwork-up.GBManalysisdemonstratedafocusofnecrosis,cellularatypia,evidenceof

pseudopalisading,andmicrovascularproliferation.ThesefeaturesaretypicalofGBMtumors.

Discussion

Among the various case reports on the phenomenon of simultaneous development of two

primaryintracranialtumors,severalhypotheseshavebeenposited.Recentpublicationssupportthe

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commonbeliefthatchancerepresentsthepredominantdrivingforcewhilealternativelyproposingthe

ideathattreatmentmethodologiesforonetumormaypotentiatethedevelopmentoftheother,either

becauseofthecarcinogenicpotentialoftheantineoplastictreatmentitselforpossiblyduetoshared

oncogenicpathways[3].Historically,therehavebeenafewcasereportsofGBMarisingincloseproximity

toapreviouslyresectedorradiotherapy-treatedmeningioma[4,5].

Closeproximityofthesetumorsalsoraisessuspicionofasharedcommonmolecularpathwayin

their pathogenesis[6]. One signaling molecule that may play a role in the development of these

simultaneoustumorsisplateletderivedgrowthfactor(PDGF).PDGFreceptorαandβwerefoundtobe

overexpressedincases of dual tumor development, suggesting their involvement in the oncogenic

signaling cascade. Furthermore, vascular endothelial growth factor (VEGF) expression has been

observedinsuchcases,illustratingapro-oncogenicangiogeniceffect.Receptortyrosinekinase(RTK),

Notch,andWntabnormalitieshavealsobeenfoundincasesofsimultaneousGBMandmeningiomas.

Epidermalgrowthfactorreceptor(EGFR),acomponentof theRTKpathway,hasbeenimplicated in

gliomagenesisandhasbeenfoundin20%ofbenignmeningiomas[3,7].Li-Fraumenisyndromehasalso

beentiedtoacaseofsimultaneousGBMandmeningioma,indicatingthatthep53pathwaymaybejustas

importantforthedevelopmentofthesedualprimarytumorsasitiswithothermalignancies[8].

Ourpatientpresentedwithtumorsthatweregeographicallydistant–beinglocatedinthefrontal

andparieto-occipitalareasoftheoppositehemispheresofthebrain.Thefactthatthemeningiomawasat

alaterdevelopmentstagecomparedtotheGBMraisesthepossibilitythatovertimethemeningioma

might have changed the neural and immunological landscape of the brainwhich in turnmay have

facilitated the subsequent rapid development of the GBM. Furthermore, previous reports involved

tumors that presentedwith similar size and stage.Our patient's tumorswere not only at different

locations,butalsoofvastlydifferentsizesandstagesofdevelopment.Ultimately,theclearpresentation

ofsymptomsfromthegiantmeningiomaanditsdistantlocationfromtheultimatelyidenti�iedGBM

preventedsimultaneouspathologicaldiagnosisandtreatmentofbothlesions.

Figures

Figure1:Pre-operativeMRI of the giantMeningioma:A)Axial T2weightedMRIwith contrast of the giant

meningioma in the right frontal lobe showingmasseffect andmidline shift;B)AxialT2weightedMRIwith

contrastshowingasmallringenhancinglesionintherightparieto-occipitallobe.

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Figure2:Postresectionpathologyofthegiantmeningioma:A)Grossresectionmass;B)H&Estainoftumor

parenchyma;C)H&Estainofarchitectureofthetumordemonstratinginvasionofthebrainparenchyma;D)H&E

stainoftumorperipherydemonstratingvascularinvolvement.

Figure3:SubsequentMRI revealing a signi�icantlydevelopedGlioblastomaMultiforme in the right parieto-

occipital lobe:A)AxialT2weightedMRIwithcontrastshowmasseffectand lateralventricularcompression

withintherightparieto-occipitallobe;B)AxialT2weightedMRIwithcontrastshowingcontralateralhemisphere

involvement-aclassic“butter�ly”sign-andmasseffect

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Conclusion

The case presented highlights the complexity of patients presenting with neuro-oncologic

diseaseandtheneedtosystematicallyaddressindividualissuesattheirindividualappropriatetime.The

patientpresentedwithsymptomsthatwerecompletelyrelatedonlytotheverylargebenigntumor,but

onimagingatpresentationalsohadconcernforCNSmalignancy.Closeclinicalandradiologicalfollowup

are imperative to try to maximize outcomes for patients with potential synchronous tumor

presentations.Unfortunatelyinthiscasethepatient'sclinicalconditionneversuf�icientlyimprovedto

allowfurthertreatmentofwhatwasultimatelydeterminedtobeincidentalglioblastoma.

References

1.SackettJ,StenwigJ,SongsirikulP.Meningealandglialtumorsincombination.Neuroradiology.1974;7:153–160.

2.MaiuriF,CappabiancaP,IaconettaG,etal.Simultaneouspresentationofmeningiomaswithotherintracranial

tumours.BrJNeurosurg.2005;19:368-375.

3.SahucP,JoubertC,NguyenA,etal.GlioblastomaSecondarytoMeningioma:ACaseReportandLiteratureReview.

WorldNeurosurg.2016;S1878-8750:31173-1.

4.PereiraE,DabbousB,QureshiH,etal.Rapiddevelopmentofglioblastomaatthesiteofatypicalmeningioma

resection.BrJNeurosurg.2010;24:471-473.

5.OhbaS,ShimizuK,ShibaoS,etal.Aglioblastomaarisingfromtheattachedregionwhereameningiomahadbeen

totallyremoved.Neuropathology.2011;31:606–611.

Figure 4:Postmortem images and pathological analysis: A) Gross picture of GBMdemonstrating extensive

bilateralhemisphericinvolvementongrosspathology;B)H&Estainoftumorparenchymademonstratingafocus

ofnecrosisandevidenceofpseudopalisading;C)HighpowerviewofH&Estaintumorparenchymademonstrating

cellularatypiaandneoplasticproliferation;D)H&Estainofgrosstumordemonstratingangiogenicproliferation.

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6.NestlerU,SchmidingerA,SchulzC,etal.Glioblastomasimultaneouslypresentwithmeningioma-reportofthree

cases.ZentralblNeurochir.2007;68:145-50.

7.NakayamaY,SueishiK,FukushimaT,etal.Localizationofplatelet-derivedendothelialcellgrowthfactorin

humanglioblastomaandmeningioma.NoshuyoByori.1994;11:187-91.

8.RieskeP,ZakrzewskaM,BiernatW,etal.Atypicalmolecularbackgroundofglioblastomaandmeningioma

developedinapatientwithLi-Fraumenisyndrome.JNeurooncol.2005;71:27-30.

ManuscriptInformation:Received:August04,2017;Accepted:December04,2017;Published:December28,2017

1 1 1 2 3Authors Information: Tarek Mansour ; Luke Mugge ; Manish Karamchandani ; Robert Mrak ; Kevin Reinard ; Jason1Schroeder *

1DepartmentofSurgery,DepartmentofNeurologicalSurgery,UniversityofToledoMedicalCenter,3000ArlingtonAve,

Toledo,OH436142DepartmentofPathology,UniversityofToledoMedicalCenter,3000ArlingtonAve,Toledo,OH436143DepartmentofNeurologicalSurgery,Promedica,2142NCoveBlvd,Toledo,OH43606

Citation:MansourT,MuggeL,KaramchandaniM,MrakR,ReinhardK,SchroederJ.Glioblastomamultiforme:Anincidental

�inding?.OpenJClinMedCaseRep.2017;1349.

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