JournalofCardiologyCases7(2013)e29–e33
Contentslistsavailableatwww.sciencedirect.com
Journal
of
Cardiology
Cases
jo u r n al h om epa g 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
A
primary
cardiac
osteosarcoma:
Case
report
and
review
of
the
literature
Cristian
A.
Aguilar
(MD)
a,∗, Jean
A.
Donet
(MD)
b,
Carolina
I.
Galarreta
(MD)
c,
Alejandro
Yabar
(MD)
aaDepartmentofPathology,HospitalEdgardoRebagliatiMartins,Lima,Peru
bDepartmentofMedicine,UniversityofMiami–JacksonMemorialHospital,Miami,FL,USA cDepartmentofPediatrics,UniversityofVirginia,Charlottesville,VA,USA
a
r
t
i
c
l
e
i
n
f
o
Articlehistory:
Received1August2012 Receivedinrevisedform 19September2012 Accepted27September2012
Keywords:
Cardiactumors
Primarycardiacosteosarcoma Leftatrium
a
b
s
t
r
a
c
t
Primarycardiacosteosarcomaisarareandaggressiveneoplasmthatcanbedifficulttodiagnose.We
reportacaseofapreviouslyhealthy49-year-oldwomanwhopresentedwithdyspnea,atrialflutter,
andheartfailure.Amasswasvisualizedinherleftatriumbyechocardiographyandcardiaccomputed
tomography,andthediagnosisofcardiacmyxomawasraised.Thepatientsubsequentlyunderwent
surgicalresectionofthemassandatrialreconstruction.Surprisingly,histologicalandimmunohistological
analysesrevealedthemasstobeanosteosarcoma.Thepatientreceivedchemotherapyandradiotherapy.
Eightmonthslater,shehasshownevidenceoflocalrecurrence.Webrieflydiscussprimaryosteosarcomas
inthecardiaccavityandtheirmanagement.
<Learningobjective:Primarycardiactumorsareveryrareandmostlikelybenign.Malignanttumors
constitutelessthan25%ofprimarycardiacneoplasms.However,bothprimarysarcomasandbenign
tumorsareoftenfoundintheleftatrium.Asaconsequenceoftheirlocationandsimilarclinical
pre-sentation,primarycardiacsarcomascanbeeasilyconfusedwithabenignmyxoma,thereforeabnormal
imagingfeatures(immobilityofthemass,neovascularity,multicentricity,calcificationandinvasioninto
theheartstructures)shouldraisesuspicionforacardiacsarcoma.>
©2012JapaneseCollegeofCardiology.PublishedbyElsevierLtd.Allrightsreserved.
Introduction
Mostcardiactumorsaremetastatictumors,whichare20–40 times more commonthan primary tumors [1,2].Most primary tumorsoftheheartarebenign,withatrialmyxomasbeingthemost common.Primarymalignanthearttumorsconstitutelessthan25% ofallprimaryhearttumors[3],withtheirprevalencerecordedas between0.001%and0.030%inoneautopsyseries[2].
Sarcomas, including angiosarcomas, leiomyosarcomas, and undifferentiatedsarcomas[3],makeupthebulkofmalignant car-diactumors. Primarycardiac osteosarcomas areextremely rare andaccountfor<10%ofallprimarycardiactumors[3,4].Primary cardiacosteosarcomasexhibit apredilectionfor theleftatrium, whereas the majority of metastatic cardiac tumors (including metastaticosteosarcomas)commonlyarisefromtherightatrium
[4].Clinicalmanifestationsdependontheanatomicalsiteoforigin andthereforecanmimicdifferentcardiacdiseases(heartfailure, valvulopathy,arrhythmia,etc.)[2–4].
Osteosarcomasareaggressivewithahighincidenceof recur-rence and metastasis. Even though complete resection can be achievedinsomecases,long-term resultsare usuallypoor.We presentacaseofaleftatrialosteosarcomainanadultPeruvian
∗Correspondingauthor.
E-mailaddress:[email protected](C.A.Aguilar).
woman with local recurrence despite aggressive surgical and chemoradiotherapeuticmanagement.
Casereport
A49-year-oldpreviouslyhealthywomanpresentedwith pro-gressive dyspnea, orthopnea, and palpitation for eight weeks. Cardiacauscultationrevealedasystolicmurmur grade3/6over theleftsternalborder.Theelectrocardiogramshowedatrialflutter at 128bpm with rapid ventricular response. Laboratory inves-tigations,including complete bloodcell count,electrolytes,and liverenzymeswerewithinnormalrange.C-reactiveproteinwas 16.1mg/dl,lactatedehydrogenaselevels937U/land N-terminal-pro-B-typenatriureticpeptide1896pg/ml.
TransthoracicDoppler-echocardiographyrevealeda heteroge-neous mass in theleft atrium, adhering to theatrial wall and posteriorleafletofthemitralvalvecausingmoderatemitral steno-sisandmildpulmonaryhypertension(Fig.1).Cardiaccomputed tomography(CT)confirmedthepresenceofa solidmasswithin theleftatrium.SystemicCTexaminationfromtheheadtothelower limbsdidnotshowmetastaticdisease.Adiagnosisofatrialmyxoma wasconsideredandsurgeryscheduled.Intraoperative examina-tionrevealedthetumortobeattachedtotheposteriorwallofthe leftatriumand theposterior mitralleaflet.Theatrial masswas partially resected and the atrium reconstructed. Complete resection was not achieved due to the tumor’s extension and
e30 C.A.Aguilaretal./JournalofCardiologyCases7(2013)e29–e33
Fig.1.Top:echocardiographicimagesshowedalargeheterogeneousmasscausingmoderatemitralstenosis.Bottom:cut-sectionofthetumorwashomogeneously grayish-brownwithfocalareasofhemorrhage.
Fig.2.Hematoxylinandeosinstain(20×magnification)revealedosteoidformationandpleomorphicsarcomatouscellularproliferation.
C.A.
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Table1
Reportedcasesofprimarycardiacosteosarcomatodate.
Author Year Sex/age Location Presentation Histopathology Metastases
Cumming[5] 1957 M/47 Leftatrium,pulmonaryvein Hemoptysisanddyspnea Osteosarcoma None
Dorney[6] 1967 M/45 Interatrialseptum Pulmonaryedema Osteosarcoma,osteoclastoma Posteriormediastinum
Lowry[7] 1972 M/29 Interatrialseptum Congestiveheartfailure Osteosarcoma,chondrosarcoma Lung,liver,andintestine
Yashar[8] 1979 M/17 Leftatrium Mitralstenosis Osteosarcoma,chondrosarcoma Recurrence(5m),lungandanterior
mediastinum
Marvasti[9] 1985 M/56 Leftatrium Dyspnea Osteosarcoma,fibrosarcoma Bone
Burke
[4] 1991
M/24 Leftatrium Syncope Osteosarcoma,chondrosarcoma None
F/43 Leftatrium Myxoma Osteosarcoma,chondrosarcoma Thyroid
F/57 Leftatrium,pulmonaryvein Dyspnea Osteosarcoma None
F/40 Leftatrium Pulmonaryhypertension Osteosarcoma,fibrosarcoma –
F/24 Leftatrium,pulmonaryvein – Osteosarcoma –
M/67 Leftatrium Dyspnea Osteosarcoma,chondrosarcoma Lung
M/45 Leftatrium Myxoma Osteosarcoma,Chondrosarcoma –
F/18 Leftatrium Congestiveheartfailure Osteosarcoma,fibrosarcoma Recurrence(30m)
F/23 Mitralvalve Mitralstenosis Osteosarcoma Skin
Dan[10] 1997 F/32 Leftatrium,mitralvalve Transientischemicattack Osteosarcoma,fibrosarcoma Pleural,muscle,andbrain
Jahns[11] 1998 F/66 Leftatrium Syncope Osteosarcoma,chondrosarcoma,
angiosarcoma
Kidney
Zanella[12] 1998 M/32 Leftatrium,pulmonaryvein Dyspneaandsyncope Osteosarcoma,fibrosarcoma Mediastinalvessels
Minami[13] 2000 F/54 Leftatrium Congestiveheartfailure Osteosarcoma None
Yamagishi[14] 2000 F/30 Rightventricle Dyspnea Osteosarcoma None
Nowrangi[15] 2000 M/64 Leftvenricle Ventriculartachyarrhythmia Osteosarcoma Lung
Lurito[16] 2002 M/14 Rightatrium Congestiveheartfailure Osteosarcoma None
Mathur[17] 2005 M/35 Leftatrium Cardio-pulmonaryarrest Osteosarcoma,chondrosarcoma Recurrence(12m)
Koc¸ak[18] 2006 F/34 Leftatrium Dyspnea Osteosarcoma None
Bae[19] 2006 F/52 Leftatrium,mitralvalve Congestiveheartfailure Osteosarcoma,chondrosarcoma None
Sogabe[20] 2007 F/68 Rightventricle,pulmonaryartery Pulmonarythromboembolism Osteosarcoma Recurrence(6m)
Takeuchi[21] 2007 M/22 Leftatrium Congestiveheartfailure Osteosarcoma Brain,bone,andkidney
Zhang[22] 2008 M/41 Rightventricle Dyspnea Osteosarcoma,chondrosarcoma None
Parwani[23] 2008 F/50 Leftatrium Dyspnea Osteosarcoma Recurrence(48m),intestinal
Forslund[24] 2008 M/75 Rightventricle Dyspneaandperipheraledema Osteosarcoma None
Cabezas-Rodríguez[25] 2009 M/27 Leftatrium Pulmonaryedema Osteosarcoma None
Dohi[26] 2009 M/20 Rightatrium Dyspneaandperipheraledema Osteosarcoma,chondrosarcoma None
Luo[27] 2010 F/42 Leftatrium Dyspneaandchestpain Osteosarcoma None
Gomez-Rubin[28] 2010 F/70 Leftatrium Dyspnea Osteosarcoma Recurrence(11m),bone
Ahn[29] 2011 F/47 Leftatrium Dyspnea Osteosarcoma Bone
Ye[30] 2011 F/42 Leftatrium Dyspnea Osteosarcoma,chondrosarcoma None
Hashimoto[31] 2011 M/67 Leftatrium Congestiveheartfailure Osteosarcoma Intestinal,peritoneal
e32 C.A.Aguilaretal./JournalofCardiologyCases7(2013)e29–e33
Fig.4.Thoraciccomputedtomographyimagesshowedalocalrecurrence8monthslater.Top:recurrentleftatrialmass(arrow)appearedadherenttotheposteriorwall. Bottom:anewtumor(arrowhead)appearedovertherightatriumandcompressedthesuperiorvenacava.
adhesiontoadjacentstructures.Thepatienttoleratedthesurgery wellandwasdischargedhomeinstablecondition.
Macroscopically,theexcisedmass measuring2.5cm×2cm× 1.5cm was grayish-brown in color, firm in consistency, and contained an area of hemorrhage on the cut section (Fig. 1). Histopathologicalanalysesrevealedpleomorphicsarcomatouscell proliferation,eosinophilicosteoidandboneformation(Fig.2).At 20×magnification,manymitoticfigureswerenoted(Fig.3),along withfociof hemorrhage.Immunohistochemicalstudiesshowed tumorcellswerepositiveforvimentin,butnegativeforcalretinin, smoothmuscleactin,desmine,cytokeratin,andS-100(Fig.3).
Post-operatively,thepatientreceivedchemotherapyconsisting ofifosfamideanddoxorubicin,aswellasradiotherapy amount-ingtoatotal doseof45Gyover25sessions.Periodiccheck-ups withCTscanassessmentwereperformed.Eightmonthsafterthe surgery,thepatientpresentedtotheemergencyroomwitha his-toryofshortnessofbreathand10kgweightloss.CardiacCTshowed theemergenceoftwonewmasses.Onemasswaslocatedinthe rightatriumwithcephalicextensiontowardsthemediastinumand compressionofthesuperiorcavavein.Theothermassappeared adherenttotheposteriorwalloftheleftatrium(Fig.4).Atthis time,thepatientwasadmittedtohospitalforsupportivecare.
Discussion
Primary cardiac osteosarcomas are uncommon tumors, accountingforonly3–9%ofallcardiacsarcomas[4].In1957,the
firstreportonprimarycardiacosteosarcomawaspublished[5]. Sincethen,fewerthan50casesofprimarycardiacosteosarcomas havebeenreported[4–31].Thesetumorsareslightly more fre-quentinwomen,withtheaverageageatdiagnosisbetweenthe 5thand6thdecadeoflife(range14–75years)(Table1).
Thereisnoevidencethatprimarycardiacosteosarcomas repre-sentmalignanttransformationofbenigntumors,despitethefact thatbothosteosarcomaandbenigntumorareoftenfoundintheleft atrium[9,11].Thetumor’scelloforiginhasyettobeclearly identi-fied.Currently,itisbelievedthattheyarisefromundifferentiated mesenchymalstemcellsintheendocardiumthattransforminto activeosteoblastssecondarytoover-expressionofspecificgenes
[12,24].Clinicalmanifestationsofcardiactumorsdependontheir
anatomicallocationandreflectthedegreeofobstruction,invasion, andembolization ofspecificintracardiacstructures[4,16].Most patientspresentwithdyspneasecondarytomitralvalve obstruc-tion,althougharrhythmiasandpericardialtamponadeareseenas
well[3,4,28].Ourpatientpresentedwithheartfailure,arrhythmia
(atrialflutter)andvalvulopathy(mitralstenosis).
C.A.Aguilaretal./JournalofCardiologyCases7(2013)e29–e33 e33
masswithdensecalcification[12].However,calcificationmayalso beminimalorabsent(asinourcase),andisseeninothertypesof cardiactumorsincludingmyxomas,fibromas,rhabdomyomas,and teratomas[1,2,32].Unambiguousimaging-baseddiagnosis there-fore remains challenging, with serial echocardiograms and CTs beingthemostreasonablestrategytodifferentiatemyxoma-like lesions.
Thespecificdiagnosisofosteosarcomaisestablishedthrough histologicalandimmunohistochemicalstudies.Osteosarcomasare a heterogeneous group of tumors containing malignant, bone-producingcells[3,4,12].Macroscopically,thetumormaybewell circumscribedandpseudoencapsulated,withinfiltrationintothe surroundingtissues.Calcification,necrosis,orhemorrhagewithin thetumorcanbeseen.Onhistology,thetumorcontainsvariable amountsofspindlecells,osteoid,bone,andcartilage.Depending on the predominant component, osteosarcomas can be sub-groupedintoosteoblastic,chondroblastic,and fibroblastictypes
[4,12]. Recognitionof a sarcomatoidtumorfeaturing malignant
osteoidallowsconfidentidentificationofosteosarcoma[12]. Mul-tiple previous studies have established the similarity between immunophenotype of extra-skeletal osteosarcomas and skele-talosteosarcomas[33].Thesetumorsareuniformlypositive for vimentinandsometimesshowpositivityforalpha-actinsmooth muscle[4,12,22].Burkeetal.reportedthathistologicalgradingis usefulforpredictingoutcome,withincreasednuclearatypia cor-relatingwithaworseprognosis[3].Severenuclearatypiaandhigh mitoticactivitywereobservedinourcase,andthepatientshowed localtumorrecurrence8monthsaftersurgery.
Osteosarcomasgrowrapidlyandbehaveaggressively. Recur-renceand metastasisarecommonfeatures of cardiac osteosar-comas. Theprognosisispoorwitha survival rateofabout15%
[3].Bettersurvivalratesareassociatedwiththeabsenceof necro-sisandlowmitoticcount.However,thelattermayreflect early diagnosis rather than different behavior. In addition, metasta-sis to distant organs including the skin, brain, thyroid, lung, stomach, liver, kidney, muscle, and bone have been reported
[4,7,10,11,15,21,28,29,31].Nostandardtherapyexistsduetothe
tumor’slow incidencerate.Since cardiacmuscleexhibitsa low tolerancetochemotherapy,surgeryisthefirst-linetreatmentfor malignantcardiactumors,andistheonlytherapythathas demon-stratedprolongedsurvival in thesepatients[1].Recently, heart transplantationhasemergedasanalternativeapproachfor unre-sectabletumors,inpatientswithnoevidenceofdistantmetastasis
[34].
Insummary,asaconsequenceoftheirlocation,primaryatrial cardiacosteosarcomacanbeeasilyconfusedwithabenign myx-oma,thereforeabnormalimagingfeaturesshouldraisesuspicion foracardiacsarcoma.Duetotheusuallyaggressivebehaviorofthis tumor,earlydetectionandaggressivesurgicalresectionmayresult inalongersurvivaltime.
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