罕见的老年患者左眼眶横纹肌肉瘤1例首席医学网2009年03月17日11:07:41Tuesday中华临床医师杂志征稿内科临床新进展研讨班重症与血流动力学大会血液净化技术学习班医学类核心期刊征稿第六届世界中医药大会2009世界高血压大会第四届中国国际白血病急危重病护理交流会IOF亚洲骨质疏松班2009年中国药学大会医学影像学术交流会结直肠肛门外科会议口腔正畸学术会议征稿广东研究生学术论坛
作者：OmarMIsmaeel,MIbrahim作者单位：马来西亚吉兰丹，马来西亚理科大学医学院眼科
加入收藏夹【摘要】 报道罕见的老年患者的左眼眶横纹肌肉瘤1例，表现为严重的眼球突出及真菌样生长的肿块。一位66岁的马来女性，鼻衄8mo后出现左眼严重的突眼和真菌样生长的肿块。活检显示小泡型横纹肌肉瘤的组织学特征。
【关键词】横纹肌肉瘤;成年人;眼眶
Rhabdomyosarcoma（RMS）comesfromGreekwordsrhabdomeansrodshape,myomeansmuscle.ItwasfirstdescribedbyWeberin1854,butitwasStoutwhogaveclearhistologicaldefinition.Theyappearfromprimitivemusclecells[1].TheocularregionparticularlytheorbitalsofttissuesrepresentamajoranatomiclocationforRMS[2].
OrbitalRMSisoneofthefewlifethreateningdiseasesseeninitiallybyophthalmologistandpromptdiagnosisandtreatmentcansavethelifeoftheaffectedpatient.RMSisthemostcommonsofttissuesarcomainthepediatricpopulation.Itaccountsfor5%ofallchildhoodcancerandforabout20%ofallmalignantsofttissuetumorThepleomorphictypeoccursmoreofteninadultsbuttheembryonalandalveolartypesmainlyoccurininfantsandchildren.TheheadandneckRMSusuallyappearinthefirstdecadeoflife.
TheprimarysitesofRMSincludeheadandneckarea45%,trunk40%andextremities15%,about25%35%ofheadandneckRMSariseintheorbit.SeveraldistincthistologicalgroupshaveprognosticsignificanceincludingembryonalRMSwhichoccursin55%ofpatientswhereasthebotryoidvariantoccursin5%ofpatients,alveolarin20%andundifferentiatedin20%.Treatmentresponsesandprognosisvarywidelydependingonlocationandhistology.
ThecauseofRMSisunknown.Thealveolarvariantisusuallyassociatedwithoneoftwochromosomaltranslocationsnamely2;13or1;13.TheseresultinfusionoftheDNAbindingdomainoftheneuromusculardevelopmentaltranscriptionfactorsencodedbyPAX3onchromosome2orPAX7onchromosome1.Theresultinghybridmoleculeisapotenttranscriptionactivator.Itisbelievedtocontributetothecancerousphenotypebyabnormallyactivatingorrepressingothergenes.
Approximately87%ofpatientsareyoungerthan15yearsand13%areaged1521years.RMSrarelyaffectsadults.Twopeaksincidencestendtobeassociatedwithdifferentlocations;patientsage26yearstendtohaveheadorneckorGUtracttumors,whereasadolescent1418yearstendtohaveprimarytumorsinextremities,truncalorparatesticularlocation.Prognosiscanalsoberelatedtothesizeoftumors.Tumoursizemorethan5cmisassociatedwithworsesurvival.NodalinvolvementappearstobeanadverseprognosticfactorinbothadultandpediatricRMS,whilepresenceofmetastasisissignificantlyassociatedwithdeath[3].
CASEREPORT
A66yearoldMalayladypresentedwithhistoryoffrequentheavyepistaxisfromleftnostrilforabouteightmonthsassociatedwithmildswellingoflefteye.Theproptosisgraduallyincreasedinsizewithcompletelossofvisioninlefteye.Hergeneralhealthwaspoorandtherewassignificantlossofweight.
Onocularexaminationthereisseverenonaxialproptosisoflefteyewithsevereconjunctivalchemosisandfungatingmasslesionpushingtheeyeforwardanddownward（Figure1）.ThevisioninlefteyewasNPLandtheorbitwasfrozen.Neckexaminationrevealedbilateralpalpablemultiplelymphnodemassesatcervicalandsubmandibularregions.Therighteyewasnormal.AbiopsytakenfromthemassandhistopathologicalexaminationshowedRMSofalveolartype.CTscanshowedahugemassfillingtheleftorbitalcavitywithsomeofthemassprotrudedoutsidethecavity.Theleftglobeispushedoutsidefromitscavityanddistortedinshape.ThemassextendsintonasopharynxwithobliterationofbothfossaofRossenmullerandintoleftmaxillarysinusandbothnasalcavity,superiorlythemassinfiltratesintotheethmoidal,sphenoidaandfrontalsinusesandinvolvingthelefttemporallobe,suprasellaryregionandcavernoussinusesespeciallyonleftside.（Figure2）.
Thepatientwasstartedoncytotoxicchemotherapyintotwophases.InphaseoneshereceivedfourcyclesofAdriamycin60mg,Vincristine2mgandcyclophosphamide1.2mgandinFigure1Severefungatingmasswithnonaxialsevereproptosis secondphaseshereceivedfourcyclesofMesna,EtoposideandIfosfomide.Treatmentwascompletedover6monthduration.Subsequentlythepatientwaslosttofollowup.
DISCUSSION
RMScommonlyaffectschildrenandyoungadultbutextremelyrareinelderlypeople.Inadultpopulationtwothirdoftissuesarcomaariseintheextremities[4].OrbitalRMScompriseof7%ofallRMS[5]andaccountsfor1%3%ofbiopsiedorbitalmassesinallagegroupsandform4%6%ofbiopsiedorbitalmassesinchildren.
OrbitalRMSisprimarilyadiseaseofyoungchildrenwithmeanageatdiagnosisof8years;howeveritcanoccuratanyage.Thereisslightpredilectionformaleswithroughlya5∶3maletofemaleratio.Thereappearstobenoracialpredispositionandthetumorisinvariablyunilateral.Mosttumorsareretrobulbarresultinginproptosisbutitcanarisefromextraconalspaceespeciallysuperiororsuperonasalarea[6].TheclassicalveolarRMSiscomposedofnetsofpoorlydifferentiatedcellswithcentrallossofcellularcohesionsurroundedbyaframeworksofdensefibrousseptatheseformingirregularalveolarspaces.Alveolartumorsaremorecommonamongadolescents,oftenariseintheextremitiesandcarryaworseprognosis.EmbryonalRMSisbyfarthemostcommonvariantfoundintheheadandneckregionincludingtheorbit.RMSarerareinpatientsolderthan40years,mostinthisagegroupareofthepleomorphicsubtypewithareportedmedianagerangeof5056years[7].In1962PorterFieldandZimmermanrefutedtheprevailingassumptionthatembryonalRMSoriginatefrompreformedmuscle.ItisnowwidelybelievedandacceptedthatembryonalRMSarisesfromundifferentiatedmesenchymalcellsthatpossessthecapacitytodifferentiateintostriatedmuscle.TheadultRMSarisesfromvoluntarymusclesandisextremelyraresincefullymaturemusclecellsarenotpronetomalignantchanges[8].PatientswithorbitalRMSgenerallypresentwithproptosisin80%100%andglobedisplacementin80%.Painisasymptomin10%ofcasesanditusuallyoccursinmoreadvancedcases.Ocularmotornerveinvolvementresultinophthalmoplegiabutrecoveryafterinitiationofchemotherapyisalmost100%duetoreductionoftumorsizethatresultinrelievecompressiononthenerve.Incontrasttoocularmotilitytheprognosisforvisualrecoveryismuchworsewhichisduetoopticatrophy[9].Visualimpairmentisusuallyminimaluntiltumorsbecomeadvanced.ConcerninganatomicallocationRMSintheorbitproducesearlyocularsymptomsandsignsascomparedtotumorsinthemoreoccultlocationsandthispermitsearlierrecognitionofthetumor.Inadditiontherearefewlymphaticchannelsintheorbitalareaandthereforeearlylymphnodemetastasisrarelyoccurs.
Inadultsproptosistendstohaveslowercourseandrarelyattainsalargesize.Inregionswheremedicalcareisnotreadilyavailable,RMScanattainimmenseproportionsanddestroytheeyeandhencevisionasinourcase.CTandMRIformcentralpartinthediagnosisofRMSandusuallyappearisointenseorgivesslightlyhighersignalthantheextraocularmusclesandlowersignalthanfatonT1weightedimages,onT2weightedimagesthelesiongiveshighsignalwithrespecttomuscleandorbitalfat.OrbitalRMScaninvadeorbitalboneandextendintocranialcavity,metastasismainlytolungsandbones;regionallymphnodemetastasisisrare.DistantmetastasisfromRMSisusuallyfatalinspiteofintensivechemotherapyandsymptomatictreatment.
In1972intergroupRMS（IRS）studywasestablishedtoincreaseknowledgeandtoimprovetherapeuticresultsforRMSfromalllocations.Fourconsecutiveclinicaltrialshadbeenconductedandreported.AstagingclassificationofRMSemployedbyIRS,brieflygrouponeisdefinedaslocalizeddiseasecompletelyresected;grouptwo,microscopicdiseaseremainingafterbiopsy,groupthreeisgrossresidualdiseaseremainingafterbiopsy,groupfourisdistantmetastasispresentatonset.Thisclassificationcanassistinselectingtreatmentandinpredictingprognosis.ThisclassificationcanalsobeappliedtocasesoforbitalRMS.
Untillate1960sorbitalexenterationwasgenerallyconsideredtobethetreatmentofchoicefororbitalRMS.HoweverthemortalityrateforpatientswithorbitalRMScontinuedtobegreaterthan70%inearly1970s.Itwasgraduallyrecognizedthatorbitalexenterationdidnotprovideaffectedpatientswithabetterprognosisandtherewasagraduallytrendtowardtreatmentwithlimitedbiopsyfollowedbyvariousregimensofirradiationandchemotherapy.Hence,orbitalexenterationisrarelyperformedasprimarytreatmenttoday.Itmaybejustifiedforextremelyadvanceddiseasethathaddestroyedtheeyeasfrequentlyseeninthirdworldcountries.Inmedicallyadvancedcountriesitstillemployedforsomeaggressivetumorsthathavebeenresistanttoirradiationandchemotherapy.
Inlate1960sandearly1970ssystemicchemotherapywasincorporatedintoprotocolsfortreatmentofRMS.Thiswasusuallycombinedwithradiotherapywithcontinuedsuccess.TheagentsemployedwereVincristineandActinomycinD.In1979areviewoforbitalRMStreatedwithcombinedsurgery,irradiationandchemotherapydemonstratedcontroloftheprimarytumorandsalvageoftheeyeinover90%ofcases.
ThelatestmanagementofRMSshouldincludeanycombinationofsurgery,irradiationandchemotherapy.Surgerycanbedonebycompleteornearcompletesurgicalremovalwhenthatcanbeachievedwithoutmajordamagetovitalstructuresliketheopticnerveandextraocularmuscles.Irradiationisusedasadjuncttosurgeryorchemotherapyfortumorrecurrenceafterstandardirradiationandchemotherapyhavefailedtocontrolthetumoralthoughexternalbeamirradiationhasbeenemployedinsuchcasesimplantbrachytherapyusingaspeciallydesignedradioactiveplaquehasbeenrarelyused.
OrbitalRMShasveryfavorableoutcomewithActinomycinDandVincristine,ithasbeenshownbylateststudythatadditionofIfosfomideandEtoposidecanimproveoutcome.
Systemicchemotherapyisconsideredtheonlytherapeuticoptionforpatientspresentingwithwidelymetastaticdiseaseorwithlocallyadvanceddiseasenotamenabletosurgeryorradiotherapy[10].Forthemajorityofthesepatientscytotoxicchemotherapyshouldberegardedaspalliativealthoughinsmallsubsetofpatientslongtermsurvivalmaybeachieved.Combinationofchemotherapymayproducehigherresponserate.Recentserieshavereportedimprovementsinthe5yearsurvivalratefrom5%to15%withlocaltherapyaloneto47%to62%withmultimodaltherapy.
TheprognosisfororbitalRMShasimprovedgreatlyinrecentyears.FactorsthatappearresponsibleforbetterprognosisforRMSinorbitalregionincludethemorefavorableanatomicallocation,theearlierstageofthediseaseatthetimeofdiagnosis,morefavorabletumormorphologyandperhapspatientage.
Absenceoflivermetastasis,youngageandhistopathologygradewereidentifiedasfavorablefactorsforresponsetochemotherapy,whilepresenceofbonemarrowmetastasiswasfoundtobeanindependentcauseofadverseprognosticfactor.NodalinvolvementappearstobeanadverseprognosticfactorinbothpediatricandadultRMS.Areviewof1,415patientswithoutdistantmetastasesinIRSIandIRSIIrevealeda10%incidenceofclinicalnodaldiseaseatdiagnosisanda14%incidenceofpathologiclymphaticmetastasesatresection.Nodalinvolvementwasparticularlycommoninpatientswithgenitourinarytracttumors（prevalence24%41%）andextremitytumors（12%）,andthe3yearsurvivalratewithlocalregionaldiseasewas45%,comparedwith75%withlocalizeddisease.
Tumormorphologyalsoappearstobeanimportantprognosticindicator,withEmbryonalRMSthemostcommontypeintheorbitcarryingmorefavorableprognosis.AlveolarRMSinwhichtranslocationexistbetweentheFKHRgenelocusandeitherPAX3orPAX7thusresultinginfusionproteinwhichisassociatedwithbetteroutcome.Metastaticdiseaseatpresentationisstronglyassociatedwithpoorprognosis.Asinourcase.Despitetherecentuseofmultimodaltherapytheprognosisinolderpatientsappearstobeworsethaninchildren.Withoverallresponseratewas82%.
Increasetumorsizewasinverselyrelatedtoprognosis.The5yearsurvivalratesforpatientswithtumorslessthan5cm,510cm,andmorethan10cmwere60%,14%and0%respectively.The5yearsurvivalofthosewithorbitalalveolarRMSwas74%andembryonalRMSwas94%[11].Theembryonalcelltypeconstitutes80%oforbitaltumors.
Femalepatientshadahigher5yearsurvivalratethanmalepatientsbutthedifferencewasnotstatisticallysignificant,thereappearedtobeanassociationbetweenfemalegenderswithcompleteresponsetochemotherapy.TheSurvivalrateaftertreatmentofRMSatallsiteshasimprovedfrom25%in1970to70%in1991.
OrbitalRMShasbeenrecognizedtodisplaybetterlifeprognosisthanRMSatothersite,thetumorsdisplaystrongtendencyforlocalinvasion,localrecurrenceandhematogenousandlymphaticmetastasis.
FerrarieevaluatedthetreatmentoutcomesforadultpatientswithRMSandconfirmtherelativelypoorlongtermoutcomes.Withradioimagingstudieslargetumorsappearedaslesswelldefinedsofttissuemasseswithbonedestructionorinvasionofsurroundingstructures.ItisstillpossiblehowevertodetectbonnyinvasionbyvirtueofdestructionofbonemarrowsignalonMRIespeciallywithadministrationofcontrast.
Aftertreatmentisinstitutedcrosssectionalimagingcanbeusedtoobjectivelymonitortumorsregressionorresidualorrecurrentdisease.RMSmayoccurasmetastasistoorbitfromdistantsiteandevenafteryearsoftreatmentwhichisextremelyrare[12].5yearsurvivalrateincreasedfrom55%IRS1to71%IRS2andIRS4.
Truncalandextremitytumorsaremorecommoninadults,andtherelativeproportionofpleomorphictumorsincreaseswithage.ThelatestseriesfromMemorialSloanKettering,therelativeproportionofextremityandpleomorphictumorsincreasedwithage,andsurvivaldecreasedwithincreasingageinbothunivariateandmultivariateanalyses.
CONCLUSION
RMSisprimarilyadiseaseofchildrenandyoungadultsbutcanoccurrarelyinelderlypeoplesohighindexofsuspicionisrequiredtoestablishearlyandcorrect.Diagnosisandinitiationofappropriatetreatmentwithchemotherapy,surgeryandradiotherapybeforemetastasismakeagreatdifferenceinsavinglivesofthesepatients.
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