Rev. bras. ortop. vol.52 número4

SOCIEDADE BRASILEIRA DE ORTOPEDIA E TRAUMATOLOGIA

w w w . r b o . o r g . b r

Update

Article

Diffuse

pigmented

villonodular

synovitis

in

knee

joint:

diagnosis

and

treatment

夽

Eduardo

Frois

Temponi

,

Antônio

Augusto

Guimarães

Barros

,

Vinícius

Oliveira

Paganini

_,

_Victor

_Atsushi

_Kasuya

_Barbosa

_,

_Roger

_Badet

_,

Lúcio

Honório

de

Carvalho

Júnior

a_{HospitalMadreTeresa,BeloHorizonte,MG,Brazil}

b_{PôleOstéoArticulaireSantéetSport,BourgoinJallieu,France}

c_{UniversidadeFederaldeMinasGerais,FaculdadedeMedicina,DepartamentodoAparelhoLocomotor,BeloHorizonte,MG,Brazil}

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Articlehistory: Received29May2016 Accepted25July2016 Availableonline24June2017

Keywords:

Synovitis,pigmentedvillonodular Knee

Radiotherapy

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b

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Pigmentedvillonodularsynovitisisarareproliferativeconditionofthesynovium.Although theconditioncanpresentinanyjoint,thekneeisthemostcommonlyaffectedsite.Despite beingabenigncondition,pigmentedvillonodularsynovitisisoftenaggressive,withmarked extra-articularextensioninsomecases.Monoarticularinvolvementoccursintwoforms: localizedanddiffuse.Thelatterismorecommon,withahighrecurrencerate.Thereisno standardmethodofmanagementofthislesion.Opensurgeryisaclassicalandeffective methodfortreatment.Arthroscopicsynovectomy,however,hasgainedpopularity,andhas severaladvantagesovertheopentechniqueparticularlyinexclusivelyarticularcases.The combinedapproachissuggestedincaseswithextra-articularinvolvement.Synovectomy throughanyapproachmaypreventsecondaryosteoarthritisandsubsequentjoint arthro-plasty.Internalirradiationorexternalbeamradiationasanadjuvanttreatmenttosurgical synovectomyappearstodecreasetherateoflocalrecurrenceindiffusecases.Theauthors observedagreatheterogeneityinreportingoffunctionalresults,andspecificconclusions shouldnotbedrawn.Eachpatientshouldbemanagedinaccordancewithhis/herparticular condition.

©2016SociedadeBrasileiradeOrtopediaeTraumatologia.PublishedbyElsevierEditora Ltda.ThisisanopenaccessarticleundertheCCBY-NC-NDlicense(http:// creativecommons.org/licenses/by-nc-nd/4.0/).

夽

StudyconductedatHospitalMadreTeresa,BeloHorizonte,MG,Brazil.

∗ _{Correspondingauthor.}

E-mails:dufrois@hotmail.com,dufrois@gmail.com(E.F.Temponi).

http://dx.doi.org/10.1016/j.rboe.2017.06.008

Sinovite

vilonodular

pigmentada

difusa

no

joelho:

diagnóstico

e

tratamento

Palavras-chave:

Sinovitepigmentadavilonodular Joelho

Radioterapia

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Asinovitevilonodularpigmentadaéumararacondic¸ãoproliferativadamembranasinovial. Apesar de a doenc¸apoder estar presente em qualquerarticulac¸ão, o joelhoé olocal maisfrequentementeafetado.Aindaquedoenc¸abenigna,geralmentetemcomportamento agressivo,podeterextensãoextra-articularemalgunscasos.Oacometimento monoartic-ularocorreemduasformas:localizadaoudifusa.Aformadifusaémaiscomumetemalta taxaderecorrência.Nãohámétodopadronizadoparaomanejodessalesão.Otratamento cirúrgicoabertoéométodoclássicoeefetivo.Asinovectomiaartroscópica,entretanto,tem ganhadopopularidadeetemdiversasvantagenssobreatécnicaaberta,principalmente emcasosexclusivamentearticulares.Aabordagemcombinadaésugeridaemcasoscom envolvimentoextra-articular.Asinovectomiapodepreveniraosteoartrosesecundáriaeo subsequentetratamentoreconstrutivo.Aradioterapiausadacomotratamentoadjuvante àsinovectomiaparecediminuirataxaderecorrêncialocalnaformadifusadadoenc¸a. Osautoresencontraramgrandeheterogeneidadenaformacomoosresultadosfuncionais foramreportadosenãosedevechegaraconclusõesespecíficas.Cadapacientedeveser manejadodeacordocomsuasparticularidades.

©2016SociedadeBrasileiradeOrtopediaeTraumatologia.PublicadoporElsevier EditoraLtda.Este ´eumartigoOpenAccesssobumalicenc¸aCCBY-NC-ND(http:// creativecommons.org/licenses/by-nc-nd/4.0/).

Introduction

Pigmentedvillonodularsynovitis(PVNS)is arare prolifera-tiveprocessthataffectsthesynovialjoints,tendonsheaths, and bursas. In 1852, Chassaignac1 _{reported the first case} ofa lesion inthe flexor tendonsheath of the second and thirdfingers;thiswassubsequentlyreportedinotherjoints. In1941,Jaffeetal.2 _{coinedtheterm“pigmented} villonodu-larsynovitis”;subsequently,Granowitzetal.3 _expandedthe terminology, distinguishing the localized (LPVNS) and dif-fuse(DPVNS)formsfromothersynoviallesions.Recently,the WorldHealthOrganizationhasdefinedPVNSandgiantcell tumortobeequivalentterms.4,5

TheestimatedincidenceofPVNSranges around1.8per million.6,7 _{Itisusuallymonoarticular,affectinglargejoints.} Thekneeisthemostaffectedsite(28%–70%),butcasesinthe hip,ankle,shoulder,andelbowareoftenobserved.5,6,8_The dis-easepresentsintwoforms,localizedordiffuse,andbothtypes havesimilarappearance:asynovialmembranecharacterized by inflammation and presence of hemosiderin deposits.3,9 Microscopically,itischaracterizedbythepresenceof lipid-ladenmacrophages,multinucleatedgiantcells,hemosiderin deposits, and proliferation of fibroblastsand stromal cells. LPVNSischaracterizedbydiscreteorpedunculatednodular lesions.Inturn,DPVNS isthe mostcommonpresentation, involvingintra-articulartissues;it mayhaveextra-articular extension,behavingasachronicprocess.10–12

In the last 100 years, little progress has been made regardingtreatment.ThegoalofPVNStreatmentistoremove allsynovialtissueinordertorelievepain,decreasetheriskof jointdestruction,andpreventlocalrecurrence.Several treat-mentoptionshavebeenproposedforthisdiseaseincasesof genicularinvolvement,rangingfromobservationandradical localsurgerytototalkneearthroplasty(Fig.1).4,5,8,13,14

Etiology

and

pathophysiology

The etiology ofPVNS isstill unknown. Some authors sug-gest thatthe diseaseoccurs asaresultofbaselinetrauma andsubsequentbleedingintheaffectedjoint.13–20 _This the-ory issupportedbythe factthat patientswith hemophilia present progressivedestruction of the cartilage during the natural course of the disease. However, studies that pro-duced PVNS-like histological findings by injecting iron or bloodintothejointwereunabletoreplicatetheclassic lipid-laden histiocytes and giant cells.15 _{However, most studies} reportedahistoryoftraumainlessthanone-thirdofpatients. Abnormalmetabolic activityhas alsobeen indicatedasan adjuvant event intheinflammationobserved inPVNS,but this isan inconsistent finding.16 _{There are alsoreports in} theliteraturethatPVNSmaybeaneoplasticprocess.Several authorssuggestedthepresenceofchromosome7trisomyand clonal rearrangementsasa cause.11,17 _{Somereports, albeit} rare, indicate the occurrence of malignant transformation andmetastasesinpatientsinitiallydiagnosedwithPVNS.17,18 DespitethecasereportsofmalignantPVNSandaneuploidy, thereisevidenceagainstthetheorythatPVNSisa neoplas-ticprocess.Intheiranalysis,Oehleretal.9_{observedastrong} evidenceofchronicinflammation.Theirfindingswerebased on thepresenceofacellularmarkerofinflammationwith aheterogeneouspopulationofmononuclearcells.Theyalso postulatedthatthepresenceoflargeamountsofironinthe lesionwouldstimulatesynoviocytesandfibroblaststodevelop macrophage-likecharacteristics.

Fig.1–Diffusepigmentedvillonodularsynovitisoftheknee–preoperativeperiodofopenanterioraccesssurgery.

commonsiteofinvolvementisthesynoviumintheanterior hornregionofthemedialmeniscus.Patientswithlesionsin thislocationmaypresentsignsandsymptomssuggestiveof meniscal disease.If left untreated,LPVNS may cause pain and discomfortand limitthe patient’s activities and func-tions.Nostudies haveassessedthe long-termoutcomes in patientswithuntreatedLPVNS,probablyduetothelowrate ofrecurrenceandthefactthattheyareeasilytreated,oreven duetothelargeproportionofasymptomaticpatients.4,12,20–25 Manyauthorsagreethatthemarginalexcisionofthelesion results in good or excellent results, especially if treated early.5,7,21

DPVNS is characterized by the involvement of almost theentiresynovialtissueintheknee. Edemaand painare more significant than in LPVNS, and are generally poorly localized. DPVNS tends tobe moredestructive and conse-quentlyhaveaworseprognosis;itmaypresentextra-articular extensionatthe timeofthe primarydiagnosis or incases of recurrence.21 _{Extra-articular lesions may also involve} neurovascular structures, making surgical resection more challengingandhinderingcompleteexcision.22,25–30_Despite treatment, the recurrence rate is high, reaching around 46%.13,14,23

Clinical

presentation

PVNSistypicallyamonoarticularprocessthatusuallyaffects largejoints.PVNSgenerallyaffectspatientsinthethirdand fourthdecadeoflife.10,19_{Historically,itwasbelievedthatthis} conditionwasmorecommoninmales,butrecentstudies indi-cated nogenderpreference.6,19 _{Itsclinical courseisaslow} and insidiousonset ofpain, swelling, and stiffness in the involved joint.Diagnosis isoftendelayed orconfusedwith initialosteoarthrosis,rheumatoidarthritis,andmeniscalor ligamentousinjury.InbothDPVNSandLPVNS,symptomsare usuallyintermittent.4,12,19,20,30–36

Diagnosis

ThediagnosisofDPVNSisnotalwaysobvious.Inthestudiesby Flandryetal.,19_{only17%ofpatientswerecorrectlydiagnosed} beforereferral.19,24_{Severalimagingmodalitiesareneededto} ruleoutotherconditionsandestablishthediagnosis. Syno-vial fluid can be collected and analyzed by arthrocentesis (Table1).33–36 _{Other specificdiagnoses shouldberuledout.} DPVNSdemonstratesnormalviscositywithvariedbleeding

Table1–Classificationofthesynovialfluidoftheknee.33–36

Normal Non-inflammatory Inflammatory Infectious Hemorrhagic

Volume(mL) <3.5 >3.5 >3.5 >3.5 >3.5

Viscosity High High Low Variable Low

Color Light,colorless Lightyellowish Yellowish Variable(opaque) Red

Leuc(mm3_{) <200 <2000 5000–75,000 >50,000 Similarbloodlevel}

Pols(%) <25 <25 50–70 >70 Similarbloodlevel

Gram Negative Negative Negative Often+ Negative

Fig.2–Kneeradiographofadiffusepigmentedvillonodularsynovitisofthekneein(A)antero-posteriorand(B)profile,

evidencingareasofbonedestruction.

Fig.3–Magneticresonanceimagingofakneewithdiffusepigmentedvillonodularsynovitisoftheknee.AandB,coronal

cutinT1;C,sagittalsectioninT1;D,T1axialcutwithareasofdiffusesynovitiswithtibialandfemoralboneinvasion,

resultinginsignificantjointdestruction.

patterns,andradiographscanbeuseful(Fig.2),astheymay showperiarticularerosionswithathinlayerofreactivebone. Thelateradiographicfindingofjointspacenarrowing indi-cates loss of articular cartilage, which may be difficult to differentiatefromprimaryosteoarthrosis.Radiographic find-ings can be observed in up to 30% ofpatients.4,19,20 _More recently,magneticresonanceimaging(MRI)hasbecomethe imagingmodalityofchoicefordiagnosingDPVNS.25_Thisisa

PVNS

DPVNS

DPVNS with low risk of recurrence

Total arthroscopic synovectomy

Without adjuvant radiotherapy

Assess the use of adjuvant radiotherapy due to recurrence risk

Assess the use of adjuvant radiotherapy due to recurrence risk Total arthroscopic synovectomy, total open synovectomy or combined

with arthroscopic (case -by-case assessment) Total arthroscopic

synovectomy, total open synovectomy or combined

with arthroscopic (case -by-case assessment)

DPVNS with high risk of recurrence

DPVNS with extra -articular involvement

Fig.4–Flowchartofthetreatmentfordiffusedpigmentedvillonodularsynovitisoftheknee(theauthors’preferred

treatmentoption,basedonliteraturereview).7,14,33–36

Observation_{:Theriskofrecurrenceshouldbeassessedbasedonthedegreeofinvolvementoftheanteriorandposterior}

compartmentsofthekneejoint,theeffectiveresectioncapacityofalllesions,andthesurgeon’sexperienceinthetreatment

oftheselesions.7,14,33–36

isdescribedas“darkondark”onT1andT2images,butinitial lesionswithlesshemosiderinmayhaveahighsignalonT2 sequences(Fig.3).4,25

Treatment

of

DPVNS

Historically,non-surgicalprocedures were the treatmentof choiceforDPVNS,andledtohighratesofrecurrence.26 How-ever,advancesinsurgicaltechniquesandpostoperativecare haveconsiderablyreducedthefrequencyofrecurrenceand complications,makingsurgicaltreatmentthefirstchoicein mostpatients.5,13

Non-surgical

Thehigh rates ofrecurrenceand complications associated withDPVNSmanagementledearlyinvestigatorstoadvocate observationuntiltotalarthroplastybecamenecessary. Recur-rentcasesdiagnosedonimagingtests,butwithoutprogressive synovitis,maynotrequireanewsynovectomy.However,such patientsshouldbefollowed-upmoreclosely.2,6,26

Radiotherapymaybeindicatedincaseswheretotal syn-ovectomy and complete resectionofextra-articular lesions cannot be performed, although some studies have dis-cussedthelong-termresultsofthisstrategywhenappliedin isolation.22,27,28

Surgicaltreatment

ManytreatmentoptionshavebeendescribedforDPVNSofthe knee.However,totalsynovectomyisconsideredthebasisof treatmenttopreventlocalrecurrence.Nospecificconclusions shouldbedrawnastowhichtechniqueshouldbeused,and eachpatientshouldbemanagedaccordingtotheirparticular case(Fig.4).

Arthroscopicapproach

DPVNS,theanterior compartmentistypicallyinvolvedand requires greater technical care from the surgeon, making complementaryportalstothetraditionalportalsmade ante-riorly,andusing30◦ _and70◦ _{arthroscopes.}33–36_Patientswith

largemassesinthepoplitealfossaorextra-articular involve-mentgenerallyarenotcandidatesforexclusivelyarthroscopic approach. Arthroscopic treatment should be reserved for patientswithlimited,purelyintra-articulardisease.34–36 Dis-easeassessmentandchoiceofbesttreatmentscheduleshould be made with MRI before the definitive resection. If the arthroscopicapproachisselected,acomplete synovectomy, includingtheposteriorcompartments,shouldbeperformed inordertominimizetheriskofrecurrence.20,23,34

Twosimilar-sizedgroupsofpatientswereidentifiedinthe reviewbyAureganetal.34_{:localrecurrenceswere observed} in28 of124 patients (23%)in the open surgerygroup and intwentyof124(16%)inthegroupthatunderwent arthro-scopicsurgery,inmeanfollow-upperiodsofsixandfiveyears, respectively. Thelower recurrencerate in the arthroscopic groupcan beexplained bythe shorterfollow-up period in thisgroup.Nonetheless,ahigherrateofpostoperative com-plicationswas reportedin the groupthat underwent open totalsynovectomywhencomparedwiththegroup submit-ted to arthroscopy. Functional scores appear to be better inthearthroscopic group;however,asdiscussedearlier,no convincingconclusioncanbedrawn.Thisstudy concluded thatposterioropentreatment,togetherwithanterior arthro-scopicsynovectomy,isaviableapproachforDPVNSofthe knee,withlowrecurrenceratesandfewpostoperative com-plications.Basedontheseresults,thearthroscopicapproach for arthroscopic synovectomy is recommended whenever technically possible. Colman et al.33 _{reported 48 cases of} patientstreatedusingthearthroscopic,posterioropenwith anterior arthroscopic,or anterior open and posterior open synovectomytechniques.Recurrencerateswerelowerinthe open/arthroscopic group when compared with the arthro-scopic or with the open/open groups: 9% vs. 62% vs. 64%, respectively.Osteoarthrosisprogressionwasobservedin17% ofthetotalofpatients, 8%ofwhom underwent totalknee arthroplastyduringthefollow-upperiod.33

Althougharthroscopy is a less invasive procedure, it is notfreeofpotentialcomplications.Inadditiontotheriskof recurrence,arthroscopicexcisionpresentsthetheoreticalrisk ofjointtumordispersionandportalcontamination.Afailed arthroscopicapproachmaycauseextensivejointinvolvement andextra-articulardissemination.20,21,23,34–36

Openapproach

Theopenapproachfollowedbycompletesynovectomyisthe standardsurgicaltreatmentforDPVNSoftheknee.Patients withextensiveextra-articularinvolvementandlargemasses inthepoplitealfossaclearlyarenotsuitablecandidatesfor arthroscopicsynovectomy.Moreover,openproceduresshould be considered for patients with disease in hard-to-reach places,suchasthepoplitealtendonsheath,betweenthe gas-trocnemiusheads,and withinthe semimembranousbursa. Open treatment begins with an anterior approach, arthro-tomy,andaggressiveanterior synovectomy,followed byan S-shaped posterior approach, protecting the neurovascular

structures.Subsequently,jointandextra-articularexploration shouldbeconductedinordertoavoidanyremainingtumor tissue.9,21,23,24,34–36

Oldstudiesassessingopentreatmentreportedexcessively highratesofrecurrence.Nonetheless,inthesestudies recur-renceprobablyindicatedincompleteexcisionsofthelesions andlikelyreferredtoinadequatesurgicalexposure.Flandry etal.19reportedaseriesof25kneeswithbiopsyandproven DPVNS that were treated by double open approach. The authorsreportedarecurrencerateof8%inafollow-upof58 months.

Open treatment, however, isnot freeofrisks and com-plications.Comparedwiththearthroscopicprocedure,open synovectomy is associated with longer hospital stay and longer rehabilitation period. Oneof the maincriticisms of the open procedure ispostoperative stiffness, which often requires manipulation under anesthesia. In the study by Flandryetal.,19_{therateofpostoperativestiffnesswas24%.} Therefore,manyexpertsadvocatetheuseoflessinvasiveand lessaggressiveprocedures.19,34

Combinedopenandarthroscopicapproach

Thecombinationofopenandarthroscopicapproachhasnot beenwelldescribedintheliterature.Patientswithposterior involvementassociatedwithminimalanteriorinvolvement may benefitfrom anterior arthroscopic synovectomy com-bined with posterior open synovectomy. Another suitable scenario for the combined approach is in cases in which totalsynovectomybyarthroscopicapproachaloneis impossi-ble. Inthis scenario,severalauthorssuggest acombination of anterior arthroscopic synovectomy and open posterior synovectomy.5,7,14_{Moreover,arthroscopymayplayan} impor-tantroleinthepre-andpostoperativediagnosis,aswellasin thetreatmentofresidualdiseaseafteropensurgery.De Car-valho etal.14 _{reportedthatpatientsdiagnosedwithDPVNS} treatedwithpartialarthroscopicsynovectomycombinedwith anterior open synovectomypresented arecurrence rate of 12.5%inameanfollow-upof8.6years;nomajorcomplications wereobservedduringfollow-up.14

Adjuvantradiotherapy

Radiotherapyhasbeenusedformanyyearsasanalternative to surgical synovectomyin patients with nonspecific syn-ovitis. Radiation-induced synovectomyin the treatment of DPVNShasbeenincreasinglydiscussed,butwithconflicting results.14,23,28,29 _{From1950onwards,goodresultshavebeen} reported with use of adjuvant external radiation in the managementofrecurrentDPVNS.30_{Potentialcomplications} are associatedwithexternalradiation,includingskin reac-tions, poor wound healing, joint stiffness, and neoplastic transformation.31–36

periodof8.6years.14_Blancoetal.29_{described22patientswith} knee DPVNS treated with arthroscopic synovectomy com-bined with postoperative external radiotherapy (total dose of2600cGy).Therecurrenceratewas13.62%;thesepatients underwent a second surgical procedure. Ustinova et al.31 describedtheirexperiencewith24patientswithDPVNS. Radi-ation(intwodoses,oneof1.2–1.5cGyinfivefractionsanda focaldoseof16–20cGy)wasapplied,sincetheaffected syno-vialtissuehadnotbeencompletelyremovedduringsurgery. Norecurrenceswereobservedinthefollow-upperiod,which rangedfromsixmonthstosixyears,andoccupational reha-bilitationwasachievedin87.5%ofthepatients.31_O’Sullivan et al.22 _{also reported the cases of 14 patients with} intra-andextra-articularlesionswhoreceivedadjuvantradiation. ThoseauthorsconcludedthatafterDPVNSremoval,theuse ofmoderateexternalradiationwasveryeffectivein preven-tingrecurrence,avoidingamputationinadvancedcasesand preservinglimbfunction.

Localradiotherapycanalsobeappliedwithintra-articular radioisotopeinjection.Chinetal.21_{assessedalargenumber} ofpatients(n=40)withDPVNS,eachsubjectedtoeitheropen orarthroscopicsurgery,but whopresentedrecurrence.The numberofresiduallesionsinthegroupstreatedwith radio-therapywaslowerthanintheuntreatedgroup.Shabatetal., inameanfollow-upofsixyears,assessedtenpatientswith DPVNSwho underwent oneormorepartialsynovectomies andreceivedintra-articularinjectionofyttriumisotope(90Y; 15–25mCi)betweensixandeightweeksafterthelastsurgery. Inninepatients,noevidenceofrecurrencewasobserved dur-ingfollow-up,whereasinonepatientthediseasestabilized.32

Final

considerations

DPVNS of the knee is a rare condition in which treat-ment may be associated with a significant risk of local recurrence,postoperativecomplications,andfunctional lim-itations.Regardinglocalrecurrence,therewasnodifference intheliteraturebetweenopenorarthroscopictotal synovec-tomyforthetreatmentofDPVNS.However,alower rateof complicationswasreportedafterarthroscopicsynovectomy. IncompletesynovectomyforthetreatmentofDPVNSshould notbeperformedinisolation,duetothehighriskof recur-rence.Internalorexternalradiationasanadjuvanttreatment method to surgical synovectomy appears to decrease the rateoflocalrecurrenceincasesofDPVNS.CasesofDPVNS withextra-articularinvolvementshouldbetreatedwithtotal synovectomy, open excision of extra-articular lesions, and adjuvantradiotherapytreatment.

Conflicts

of

interest

Theauthorsdeclarenoconflictsofinterest.

Acknowledgments

ToallresearchersandtoDr.GuilhermeReisforhaving autho-rizedtheuseofthearchiveimagesinthisarticle.

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