JournalofCardiologyCases9(2014)40–43
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Journal of Cardiology Cases
jo u r n al ho m e p ag e :w w w . e l s e v i e r . c o m / l o c a t e / j c c a s e
Case Report
Primary pericardial synovial sarcoma: A case report and literature review
Tarik Chekrine (MD)
a,∗, Souha Sahraoui (PhD)
a, Siham Cherkaoui (PhD)
b, Houda Eddakkaoui (MD)
a, Hicham Labsaili (MD)
c, Soufia Marouane (PhD)
d,
Hicham El Attar (MD)
e, Soumaya Zamiati (PhD)
d, Badiae-Ezzamane Mehadji (PhD)
c, Abdellatif Benider (PhD)
aaDepartmentofRadiotherapy-Oncology,UHCIbnRochd,Casablanca,Morocco
bDepartmentofPediatricHematologyandOncology,20AoûtHospital,UHCIbnRochd,Casablanca,Morocco
cDepartmentofCardiovascularSurgery,UHCIbnRochd,Casablanca,Morocco
dCentralDepartmentofPathologicalAnatomy,UHCIbnRochd,Casablanca,Morocco
eAnatomyandPathologicalCytologyLaboratory,MoulayIdrissI,Casablanca,Morocco
a r t i c l e i n f o
Articlehistory:
Received9April2013
Receivedinrevisedform14August2013 Accepted14September2013
Keywords:
Synovialsarcoma Pericardium Treatment Prognosis
a b s t r a c t
Primarypericardialsynovialsarcomaisextremelyrare,withfewpublishedcasesintheliterature.We reportthecaseofanadolescentaged13yearswithprimarypericardialsynovialsarcomadiscovered duringtamponade,confirmedbymolecularbiology,andforwhomtreatmentcombinedradiosurgery andadjuvantchemotherapy.Theparticularityofthecasewearereportingstemsfromtheyoungageof ourpatient(13years)aswellasthedurationofremission,whichisquitelong(21months)priortoa superiormediastinalrelapsecomparedtocasesreportedintheliterature.
<Learningobjective: Synovialsarcomaisdifficulttodiagnoseandhasapoorprognosis.Here,a13- year-olddiagnosedwithprimarypericardialsynovialsarcomawastreatedwithcombinedradiosurgery andadjuvantchemotherapyleadingtocontinuousremissionfor21months.Thisregimencouldbeused tosuccessfullymanagefuturepatients.Molecularbiologyisusefulinthediagnosisofsynovialsarcoma throughtheidentificationoft(X;18)translocationinatypicallocationsasinthepresentcase.>
©2013JapaneseCollegeofCardiology.PublishedbyElsevierLtd.Allrightsreserved.
Introduction
Synovialsarcoma isa highly malignantmesenchymaltumor thatusuallyaffectsthedeepsofttissuesnearthelargejointsofthe extremitiesinadolescentsandyoungadults[1,2].Otheratypical primarylocalizationshavebeendescribed:headandneck,heart, pleura,abdomen,kidney,prostate,andvulva[1].Pericardiallocal- izationisextremelyrare[3–6].Onlyafewwell-documentedcases havebeenpublished[1,5–15].Inthismanuscriptwereportanew case.
Casereport
A13-year-oldchild,withnomedicalhistory,presentedforcon- sultationin February2011intheemergencydepartmentforan exertionaldyspneaofsuddenonset.
∗ Correspondingauthorat:183,BdMyThami,LotElMers,Casablanca20220, Morocco.Tel.:+212668466707;fax:+212522490903.
E-mailaddresses:chekrinetarik@yahoo.fr,Chekrine1@hotmail.com (T.Chekrine).
Theclinicalexaminationfoundanorthopnea,tachycardia,and pericardial friction rub on heart auscultation. The chest X-ray showedacardiomegaly,leadingtohishospitalizationinthedepart- mentofcardiovascularsurgery.
Theechocardiographyshowedpericardialeffusionintheright sub-costalarea, as wellasa 73mm×61mmrightlateral-atrial intra-pericardialmassresponsiblefordiastoliccompressionofthe rightventriclefreewall(Fig.1).Pericardialdrainagebrought500ml ofsero-hematicfluid.
Thechestcomputedtomographyscanperformedsubsequently showedanexpansiveintra-pericardialprocessincontactwiththe rightauricleandventricle(Fig.2aandb).Thepartialresectionof theintrapericardialtumorwasperformedsecondarilytoprevent heartfailureandtogainadefinitivediagnosis.Completeresection of the tumor was impossible because of the intrapericardial localizationofthetumor.Histologically,itwasamalignanttumor proliferationarranged inbundles. Thecells wereoftenspindle- shaped,withpoorlydefinedcytoplasmandelongatednucleiwith afine,dustychromatin,andmitoseswerecommon(Fig.3aandb).
Onimmunostaining,cellswerepositiveforepithelialmembrane antigen and vimentinbut negative for pankeratin AE1/AE3, CD 34, CD 45, and chromogranin. Given these morphological and 1878-5409/$–seefrontmatter©2013JapaneseCollegeofCardiology.PublishedbyElsevierLtd.Allrightsreserved.
http://dx.doi.org/10.1016/j.jccase.2013.09.005
T.Chekrineetal./JournalofCardiologyCases9(2014)40–43 41
Fig. 1.Echocardiographyshowing a right lateral atrial intra-pericardial mass (whitestar).
immunophenotypicaspects,amonophasicsynovialsarcomawith gradeIIImalignancyaccordingtotheFNCLCC (FrenchFédération NationaledesCentresdeLutteContreleCancer)systemisgiven.The diagnosiswasconfirmedby molecularcytogeneticexamination (fluorescence in situ hybridization; FISH), which showed that 65%ofcellsshowedrearrangementoftheSS18locusmolecular equivalentofthecharacteristict(X;18)translocation(Fig.4).The examination for an extra-pericardial localization particularlyin thesofttissuescamebacknegative.
Chemotherapywithfourcoursesofifosfamideanddoxorubicin treatment every three weeks was well tolerated. Radiographic
Fig.2. Chestcomputed tomography (CT)findings. (a)Plainand(b) contrast- enhancedCTimage.Intra-pericardialtumorincontactwiththerightatriumand rightventricle(arrow).
Fig. 3.(a) Overview of spindle cell tumor infiltrating pericardium tissue (hematoxylin–eosin,original40×).(b)Aphotomicrographoftheprimarypericardial tumorshowingfasciculiofthespindlecells(hematoxylin–eosin,original400×).
evaluation revealed a tumor regression greater than 50%. The patientreceivedpostoperativeradiotherapyontheheartintotal at adoseof 30.6Gyin 17 fractionswitha double exposureon thetumorbedatadoseof19.6Gyin11fractions.Monitoringby echocardiography and electrocardiography during radiotherapy
Fig.4.Fluorescenceinsituhybridizationanalysisofthetumor(FISH):bi-colorDNA probe,Breakapart,SS18locusrearrangementin18q11.2molecularequivalentof thet(X;18)translocation(arrow).
42 T.Chekrineetal./JournalofCardiologyCases9(2014)40–43 didnotobjectifyspecificabnormalities.Thepatientremainedin
continuousremission for 21 months and thepericardialtumor remainedstable.Theevolutionwasmarkedbyananteriorsuperior mediastinalrelapse forwhich thechildis receivingsecond-line chemotherapycombiningifosfamide,carboplatin,andetoposide.
After four cycles, the tumor response was less than 50%. The generalconditionofthepatientiscurrentlyunderre-evaluation byateamofsupportivecare.
Discussion
Pericardial tumors are extremely rare with an incidence of 0.001–0.28% in some autopsy sets [5]. Metastatic lesions are morecommon thanprimary lesions[16].These are dominated by mesothelioma while primitive pericardial synovial sarcoma is extremely rare[3–6] withonly 17 casesreported todate in theEnglishliterature(Table1)[1,3,5–15].Malignantspindlecell tumors, pericardialcysts, liposarcomas, lipomas, and teratomas areotherlesscommonvarietiesofprimitivepericardialtumors [14].Itisassumedthatthereisnodirectrelationshipbetweenthe synovialtissueand synovialsarcoma,thetumorderived froma synovialdifferentiatedpluripotentmesenchymalcell[17].There is a discreet male predominance, thesex ratio being2.5/1 [1], withahigherincidenceinthe3rdand4thdecade[3].Theaver- ageageofpatientsatdiagnosisis39years [1].Our patientwas 13yearsoldatdiagnosis,theyoungestamongallcasesreported intheliterature.Clinically,thesymptomsareattributedtotam- ponade[1].Dyspneaisbyfarthemostcommonsymptom.Other symptomsincludechestpain,cough,andorthopnea[1,5].Thediag- nosisisusuallyestablishedbytrans-thoracicortrans-esophageal
echocardiography, computed tomography, magnetic resonance imaging,cytologicalexaminationofpericardialeffusion,andperi- cardialbiopsy[5].Itiswellestablishedthatmagneticresonance imagingallows fora betterassessmentof heartand pericardial tumorsanddistinguishesbetweenbenignandmalignanttumors [5,18].Itiseffectiveinpost-treatmentmonitoring[6,7].Generally, apericardialmassassociatedwithapericardialeffusionshowsup.
Tumorsvaryinsizefrom6to15cm(mean10.6cm)[1].
Histologically, synovial sarcomas are classified as biphasic, monophasic,orpoorlydifferentiated[1,6,14].Thebiphasicvariant appearstobemorecommoninthepericardiallocalizationcom- paredtotheothersynovialsarcomasites[1].Mosttumorscarrya characteristict(X;18)translocation,whichinvolvesthegenesSSX1 orSSX2fromthechromosomeX(Xp11)andthegeneSYTfromthe chromosome18(18q11)[3].Morethan90%ofpatientswithsyno- vialsarcomahaveat(X;18)translocation,whichisnotassociated withothersarcomas[1].
In the case we are reporting, cytogenetics confirmed the macroscopicand microscopic findings. Themoleculardiagnosis is therefore essential especially when histological diagnosis is difficult.Inadditiontothecasewearereporting,12othercases ofprimarypericardialsynovialsarcomasreportedintheliterature wereconfirmedeitherbyreversetranscription–polymerasechain reaction(RT-PCR),orbyFISH,orby both[1,2,7,9–13].TheFISH technique hasbetter sensitivity in thedetection of thet(X;18) translocationthanRT-PCR,whilethelatterhastheadvantageof identifyinggenefusiontranscripts[1].Thedifferentialdiagnosis arises mainly with pericardial mesothelioma, which is usually associatedwithahistoryofasbestosexposureandwithadiffuse infiltrationof thepericardium.On theotherhand, thesynovial
Table1
Primarypericardialsynovialsarcoma:summaryofpublishedstudies.
Authors Sex/age
(y)
Tumor size(cm)
Histological subtype
Symptoms Molecular
biology
Treatment Evolution
Al-Rajhietal.(1999)[7] M/19 10 Biphasic Difficultybreathing t(X,18) Surgery,RT Inremissionfor12months Kojimaetal.(1999)[9] F/35 11 Monophasic Chestpain,nausea,
dyspnea
t(X,18) NA NA
Oizumietal.(1999)[12] F/19 14 Biphasic Dyspnea,asthenia t(X,18) Surgery Deceasedafter7months Anandetal.(2003)[8] M/29 8.5 Monophasic Difficultybreathing Notperformed Surgery–RT–CT Inremissionfor13months VanDerMierenetal.
(2004)[10]
M/26 NA Biphasic Tamponade t(X,18) Surgery–CT–RT Inremissionfor14years
Bégueretetal.(2005)[11] M/59 15 NA NA t(X,18) NA NA
Schumannetal.(2007)[18] F/64 NA NA Difficultybreathing, tachycardia
Notperformed Surgery NA
Hingetal.(2007)[13] M/15 NA Biphasic Cough,tachypnea, weightloss
t(X,18) CT–surgery Deceasedafter31months Korulaetal.(2009)[15] M/49 13 Monophasic Dyspnea,chestpain Notperformed Supportivecare NA
Katakuraetal.(2009)[2] F/70 13 NA Cough,dyspnea t(X,18) Surgery,palliative care
Deceasedafter79days Moorjanietal.(2009)[3] M/61 6 Biphasic Dyspnea,peripheral
edema
Notperformed Surgery–CT Inremissionafter2months Rangrezeetal.(2011)[5] M/19 15 Monophasic Cough,dyspnea,
orthopnea
Notperformed Surgery–palliative CT
Inprogress Akerströmetal.(2011)[6] F/54 11 Biphasic Malaise,fever,chest
pain
t(X,18) Surgery–CT–RT Inremissionfor22months
Chengetal.(2012)[1]
M/31 10 Biphasic Fever,cough t(X,18) CT–surgery Inremissionfor12months
M/31 8 Monophasic Fever,nightsweats, tachypnea,chestpain
t(X,18) Surgery–CT Deceasedafter27months M/38 8 Monophasic Chestpain,difficulty
breathing
t(X,18) Waitingforaheart transplant
Inremissionfor2months
Kodikaraetal.(2012)[14] M/61 5 Biphasic Discoveredat autopsy
death/hypertensive disease
t(X,18) – –
Ourcase M/13 7.3 Monophasic Dyspnea,orthopnea,
tachycardia
t(X,18) Surgery–CT–RT Inremissionfor21months anteriorsuperior mediastinalrelapse NA:notavailable;CT:chemotherapy;RT:radiotherapy;t:translocation;M:male;F:female.
T.Chekrineetal./JournalofCardiologyCases9(2014)40–43 43 sarcoma is usually a solitary mass and not associated with a
history of asbestos exposure [3]. Immunohistochemical and molecularcytogeneticstudiesconfirm thediagnosisin casesof doubt[1].
Given its rarity,synovialsarcoma of the pericardium is dif- ficult to diagnose, its primary character difficult to confirm. A secondarypericardiallesionofsofttissuesynovialsarcomashould beexcluded prior tomaintainingits primary character[16]. In ourcase,theabsence ofanextra-pericardial tumorlocalization atdiagnosisandafter21monthsoffollow-upconfirmsthepri- marycharacterofthetumor.Becauseoftherarityofpericardial synovialsarcomas, there is nostandard therapy. Treatment,as inallsofttissuesarcomas,ismultimodalcombiningsurgeryand radiochemotherapy.
Complete surgery remains the primary treatment option [10,15].Externalbeamradiationtherapyisgivenintheeventof incompletesurgicalexcision,providingbetterlocalcontrol[7,8,10].
Chemotherapyisindicated in theeventofunresectable tumors becauseofitsspreadormetastases[10].Theuseofdoxorubicin canbelimitedduetoitscardiotoxicity.Inourcase,thecombina- tionofradio-surgeryandchemotherapyallowedforloco-regional controlwithafollow-upof21months.Pazopanib,amulti-targeted tyrosinekinaseinhibitor,isanewtreatmentoptionforpatients withnon-adipocytic,metastaticsoft-tissuesarcomaafterfailureof standardchemotherapy[19].
Primarypericardialsynovialsarcomahasapoorprognosisespe- ciallywhencompletesurgicalresectionisnotpossible[8,18].Thisis explainedbythelargesizeofthelesionsandthedifficultyachieving completeresectionbecauseoftheanatomicalposition[1].Overall, survivalisshort.TheonlyexceptionisthecasereportedbyVan derMierenof a26-year-oldpatient,operated onfor a biphasic pericardialsynovialsarcomawithmicroscopicallyhealthysurgi- calresectionmargins,havingreceivedadjuvantradiotherapyand chemotherapy,and witha survival of 14 years [10].In conclu- sion,primarypericardialsynovialsarcoma isanextremely rare andaggressivetumor,withdifficultdiagnosisandpoorprogno- sis.The discovery of a pericardiallesion must first eliminate a secondarylocation.Molecularbiologyexaminationbysearching forthet(X,18)translocationcharacteristiccontributessignificantly tothediagnosis.Theparticularitiesofourobservationstemfrom theyoungageof ourpatient(13years), whiletheaverageage ofreportedcasesis39years,andtherelativelylongdurationof remissionof21months,followingtreatmentcombiningsurgery, chemotherapy,andradiotherapy.
Conflictofinterest
Authorsdeclarenoconflictofinterest.
Acknowledgments
WewouldliketothankDrH.MossafaandDrS.Defasquefor performingthemolecularlaboratorytests.
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