罕见的老年患者左眼眶横纹肌肉瘤1例

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

【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