BrazJOtorhinolaryngol.2018;84(6):790---798
www.bjorl.org
Brazilian
Journal
of
OTORHINOLARYNGOLOGY
REVIEW
ARTICLE
Solitary
plasmacytoma
of
the
jaws:
therapeutical
considerations
and
prognosis
based
on
a
case
reports
systematic
survey
夽
Eduardo
Madruga
Lombardo
a,∗,
Fábio
Luiz
Dal
Moro
Maito
b,
Cláiton
Heitz
aaPontifíciaUniversidadeCatólicadoRioGrandedoSul(PUCRS),FaculdadedeOdontologia,DepartamentodeCirurgia Bucomaxilofacial,PortoAlegre,RS,Brazil
bPontifíciaUniversidadeCatólicadoRioGrandedoSul(PUCRS),FaculdadedeOdontologia,DepartamentodePatologiaOral, PortoAlegre,RS,Brazil
Received14March2018;accepted1May2018 Availableonline11June2018
KEYWORDS Plasmacytoma; Plasmacelltumor; Multiplemyeloma
Abstract
Introduction:Solitaryplasmacytomaisararemalignanttumorofplasmacellswithnoevidence ofsystemicproliferation.Therearetwoknownsubtypes:extramedullarysolitaryplasmacytoma andsolitaryboneplasmacytoma.Theetiologyisstillunknown.Bothlesionspresentariskof progressiontomultiplemyeloma.Anumber ofapproacheshavebeenusedfor treatmentof solitaryplasmacytoma.
Objective:Tocarryoutasystematicreviewofthecasereportsdescribedintheliterature, focusingontherapeuticandprognosticaspects.
Methods:AsearchofclinicalcasereportswasperformedinthePubMeddatabaseusingMesh Termsrelatedto‘‘plasmacytoma’’underthefollowingcriteria:typeofstudy(casereport), articlesinEnglishlanguage,conductedinhumans,withnopublicationdatelimits.
Results:Ofthe216articlesfound,only21articlesmetthepre-establishedinclusioncriteria.
Conclusion:Theoccurrenceofsolitaryboneplasmacytomainthebonesofthefaceisarare conditionprevalentbetweenthe4thand6thdecadesoflife,locatedintheposteriorregion ofthemandibleinmostcases.Histopathologicalexaminationandsystemicinvestigationare mandatoryforconfirmationofdiagnosis.
© 2018 Associac¸˜ao Brasileira de Otorrinolaringologia e Cirurgia C´ervico-Facial. Published by Elsevier Editora Ltda. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/).
夽 Pleasecitethisarticleas:LombardoEM,MaitoFL,HeitzC.Solitaryplasmacytomaofthejaws:therapeuticalconsiderationsandprognosis
basedonacasereportssystematicsurvey.BrazJOtorhinolaryngol.2018;84:790---8.
∗Correspondingauthor.
E-mail:Eduardomlombardo@gmail.com(E.M.Lombardo).
PeerReviewundertheresponsibilityofAssociac¸ãoBrasileiradeOtorrinolaringologiaeCirurgiaCérvico-Facial. https://doi.org/10.1016/j.bjorl.2018.05.002
1808-8694/©2018Associac¸˜aoBrasileiradeOtorrinolaringologiaeCirurgiaC´ervico-Facial.PublishedbyElsevierEditoraLtda.Thisisanopen accessarticleundertheCCBYlicense(http://creativecommons.org/licenses/by/4.0/).
Solitaryplasmacytomaofthejaws:therapeuticalconsiderationsandprognosis 791 PALAVRAS-CHAVE Plasmocitoma; Tumordecélulas plasmáticas; Mielomamúltiplo
Plasmocitomasolitáriodemandíbula:considerac¸õesterapêuticaseprognósticascom baseemumestudosistemáticoderelatosdecasos
Resumo
Introduc¸ão: O plasmocitoma solitário é um tumor malignoraro de células plasmáticas sem evidênciadeproliferac¸ãosistêmicaeenglobadoissubtipos:plasmocitomasolitário extramedu-lar e plasmocitoma solitário ósseo. A etiologia ainda é desconhecida. Ambas as lesões apresentam riscode progressãopara mielomamúltiplo. Uma sériede abordagenstem sido usadaparaseutratamento.
Objetivo: Realizarumarevisãosistemáticadaliteraturacomenfoquenosaspectosterapêuticos eprognósticos.
Método: Realizou-seumabuscaderelatosdecasoclíniconabasededadosPubMedcomtermos debuscarelacionadoscom‘‘plasmocitoma’’sobosseguintescritérios:tipodeestudo(relato decaso),artigosnalínguainglesa,estudosrealizadosapenasemhumanos,semlimitesdedata depublicac¸ão.
Resultados: Dos216artigosencontrados,apenas21artigospreencheramoscritériosdeinclusão pré-estabelecidos.
Conclusão:Aocorrênciadeplasmocitomasolitárioósseonosossosdafaceéumacondic¸ãorara prevalenteentrea4aea6adécadasdevida,localizadanaregiãoposteriordemandíbulana
maioriadoscasos.Oexamehistopatológicoeainvestigac¸ãosistêmicasãomandatóriospara confirmac¸ãododiagnóstico.
© 2018 Associac¸˜ao Brasileira de Otorrinolaringologia e Cirurgia C´ervico-Facial. Publicado por Elsevier Editora Ltda. Este ´e um artigo Open Access sob uma licenc¸a CC BY (http:// creativecommons.org/licenses/by/4.0/).
Introduction
Solitary plasmacytoma (SP) is a rare malignant tumor of plasma cells with no evidence of systemic proliferation. When thereis systemic involvement,that is, the involve-mentofmultipleskeletalsites,thediseaseiscalledmultiple myeloma(MM),oneofthemostfrequent presentationsof neoplasiaoftheplasmacells.1
The SP presentsan incidenceof 2---5%of allneoplasms and two subtypes: extramedullary solitary plasmacytoma (ESP) and solitary bone plasmacytoma (SBP).1,2 ESP
origi-natesfrom soft tissues and is more frequent in the head andneckregion,specificallyintheupperrespiratorytract, whereastheSBPpresentsasanintramedullarybonelesion intheaxialskeletonorpelvicbones.3
Theetiologyofsolitaryplasmacytomaisunknown, how-ever, it is suggested that chronic stimulation, radiation overdose, viral infections and genetic interaction in the reticuloendothelialsystemmaycontributetothe develop-mentofthelesion.4
TheSBPhasapredilectionformalesbetweenthe6thand the7thdecadesoflife,however,itcanaffectindividualsof anyage.PatientsaffectedbySBP,ingeneral,presenta pri-marycomplaintofswellingassociatedwithminimalpain.5,6
The SBP can present two radiographic patterns: the first can be a delimited radiolucent area; the second, as a destructive lytic mass in the mandible. Microscopically, monoclonalproliferationofplasmacytoidcellswith eccen-tricnucleiandbasophiliccytoplasmareobserved.7,8
Once thebiopsyis performedandthehistopathological diagnosis of SBPis defined, it is importantto submit the patient to systemic investigation of disseminated disease
through imaging examinations of the whole body, bone marrow biopsy, complete hematological examination and electrophoresis of urine and plasma to screen proteins synthesizedbytumorcells.1,9---11
Although MM is a relatively common occurrence when comparedtootherplasmacellneoplasms,SBPintheskull bonesis arelatively rareentity withverylittlepublished literature.12Theobjectiveofthepresentstudyistoperform
asystematicreviewofcasereportsfocusingonits epidemi-ology, clinical and microscopic characteristics, aswell as itsdiagnosis, treatment, prognosisand the importanceof longitudinalclinicalfollow-up.
Methods
A systematic review of the case reports was performed from articles found in the PubMed/MEDLINE database. A searchstrategywasdevelopedusingthePubmedAdvanced Search Builder with the following combinations of the Mesh terms ‘‘Plasmacytoma’’, ‘‘Myeloma’’, ‘‘mandible’’ and‘‘maxilla’’andthederivedentrytermsinconjunction withtheBooleanoperators‘‘OR’’And‘‘AND’’,asdescribed inTable1.Theinclusioncriteriaappliedforthecasereports were:typeofstudy(casereports),inEnglishlanguageand conductedinhumans.
Results
Based on the search strategy, 216 articles were found. Applying the inclusion criteria asfilter, 114 articles were excluded. The remaining 102 articles were submitted to
792 LombardoEMetal.
Table1 SearchstrategyonPubmedAdvancedSearchBuilder. Filter‘‘Allfields’’ MeshTerm Entryterms
1 Plasmacytoma PlasmacytomasORPlasmocytomaORPlasmocytomasORPlasmaCellTumorOR PlasmaCellTumorsORTumor,PlasmaCellORTumors,PlasmaCell
Booleanoperator‘‘OR’’
2 Myeloma MultipleMyelomasORMyelomas,MultipleORMyeloma,MultipleORMyeloma, Plasma-CellORMyeloma,PlasmaCellORMyelomas,Plasma-CellOR Plasma-CellMyelomaORPlasma-CellMyelomasORMyelomatosisORMyelomatosesOR PlasmaCellMyelomaORCellMyeloma,PlasmaORCellMyelomas,PlasmaOR Myelomas,PlasmaCellORPlasmaCellMyelomasORKahlerDiseaseOR Disease,KahlerORMyeloma-MultipleORMyelomaMultipleOR Myeloma-Multiples
Booleanoperator‘‘AND’’
3 Mandible MandiblesORMylohyoidRidgeORMylohyoidRidgesORRidge,MylohyoidOR Ridges,MylohyoidORMylohyoidGrooveORGroove,MylohyoidORGrooves, MylohyoidORMylohyoidGroovesORmandibleORLowerjaw
Booleanoperator‘‘OR’’
4 Maxilla MaxillasORMaxillaryBoneORBone,MaxillaryORBones,MaxillaryOR MaxillaryBonesORMaxillaeORUpperJawORMaxilla
Booleanoperator‘‘AND’’
5 --- Solitary
selectivereadingofthetitles,whichdeterminedthe exclu-sionof78articles.Theremaining24articlesweresubmitted toanalysisoftheabstractsand,atthisstage,threearticles wereexcludedbecausetheypresentedSPlesionlocatedin ananatomicalregiondistinctfromtheoralandmaxillofacial surgeons’expertise.
The interpretativereadingof thefull case reports was carried out in 21 articles: 20 case reports and 1 case series.Thecasereportswerearrangedindescendingorder of the year of publication in two tables: one providing epidemiologicalandclinicaldataaswellastheinitial diag-nosis(Table2);theother (Table3)containinginformation regardingthedetectionofM-protein(orparaprotein), thera-peuticapproach,follow-uptime,recurrencesandevolution for MM, as well as findings considered relevant to each article.Inaddition,thecaseserieswasincludedinthe dis-cussionofthissamestudy.
Discussion
Epidemiologicaldata
ThedistributionofSBPcasesby agerangedfrom15to83 years,withameanageof54.15yearsforbothsexes,43.6 yearsformenand61.54yearsforwomen.Thehighest inci-dence of SBPoccurred between the 4th and 6thdecades of life.2,4,13---30 The distribution by gender was balanced,
accountingfor11casesinwomenand10inmen.Thesedata corroboratetheresultsobtainedbyDoresetal.12
Thepatient’sracewasreportedinonly7casereports:3 blackpatients,3Asianpatientsand1whitepatient.2,4,13---30
Althoughmostofthecasereportsdidnotreporttheraceof thepatients,apredilectionoftheSBPforwhiteindividuals isobservedintheliterature.12
Locationofthelesion
Inthecasereportsreviewed,themostcommonsiteofSBP appearancewasthemandible,morepreciselyinposterior regions.2,4,13---30ThesefindingsconfirmthosefoundbyLoh26
andPisanoetal.31
Although the literature presents pain as the main symptom.2Thepresentstudyfoundpainlessincreasein
vol-ume as the most common clinical finding. Headache and pressure sensation have alsobeen reported.25,30 The time
ofevolutionofthelesionrangedfrom15daysto72months, withanaveragetimeofevolutionof15.11months.2,4,13---31
Imagingaspectsandinitialdiagnosis
Radiographically,itwasobservedthat,inmoststudies,the solitary plasmacytoma appears as a diffuse, multilocular radiolucentlesion.Bonedestructionseemstobelimitedto themedullaryregionoftheskullbones.2,4,13---30
Only 8 case reports presented a presumptive clinical diagnosis, and the hypotheses presented were: abscess, pyogenicgranuloma,myxoma,ameloblastoma,orbital pseu-dotumorandosteosarcoma.13,15,19,20,23,25,26,29
DifferentialdiagnosisofPBSshouldbeperformedin rela-tiontootherlesionsthataresimilarintheroutineimaging exams such as ameloblastoma, keratocystic odontogenic tumor,myxoma,giantcellcentrallesion,metastatictumors, vascular malformation,sarcoma andlymphoma.32,33 Thus,
thehistopathologicalexaminationbecomesessentialforthe definitivediagnosis.
PresenceofM-protein
PlasmaproteinMorparaprotein,monoclonal immunoglob-ulin synthesized by tumor cells, was investigated in 18 cases.2,4,13---30 The presence of theM-protein wasreported
Solitary plasmacytoma of the jaws: therapeutical considerations and prognosis 793
Table2 Epidemiologicalandclinicaldata.
Reference Age(years) Sex Race Localization Clinicalaspects Evolutiontime Imagingaspects Initialdiagnosis
Cioranuetal.13
(2013)
52 M NR Zygomatic,molar
andorbitalregion, rightside
Swelling 2years Expansivemass Plasmacytoma
SAnetal.14(2013) 65 F NR Angle,ramusand
coronoidprocess ofthemandible, leftside
Swelling 2years Poorlydefined
radiolucentlesion NR Nandaetal.15 (2012) 70 F NR Fromcanineto molarwith palatine involvement,right side
Swelling 15days Mistyradiolucent
lesion
Abscess
Pintoetal.16
(2007)
65 F Black Superiorcanine
region,leftside
Swellingandpain 15days Diffuse
radiolucentlesion NR Poggioetal.17 (2007) 75 F NR Anteriorborderof themandible, rightside
Swellingandpain 3years Radiolucentlesion
relatedtoan implant
NR
Anil2(2007) 52 M NR Superiorpremolar
andmolarregion extendingtothe palate,rightside
Swellingandpain NR Diffuse
radiolucentlesion NR Cangeretal.18 (2007) 76 F NR Anteriorregionof themandible
Swelling,painand erythema 6months Multilocular radiolucentlesion NR Ozdemiretal.4 (2005)
63 F NR Palate Swelling NR Lyticbonelesions NR
Yoonetal.19
(2003)
15 M Asian Inferiormolar
region,rightside
Swelling 6years Increasein
periodontal ligamentspace betweenlower molars Granuloma pyogenic Matsumuraetal.20 (2000) 83 M NR Maxillarysinus, rightside
Swelling 1month Velvetoftheright
maxillarysinus andaspectof ‘‘honeycombs’’
Myxomaor ameloblastoma
Hoetal.21(1999) 22 M Asian Mandibularramus,
rightside
Swelling 6months Osteolyticlesion NR
Millesietal.22
(1997)
44 M NR Premolarregionto
theanglein mandible,leftside
794 Lombardo EM et al. Table2(Continued)
Reference Age(years) Sex Race Localization Clinicalaspects Evolutiontime Imagingaspects Initialdiagnosis
Kanazawaetal.23
(1993)
49 FNR Frommediumline
totheramus
ofthemandible, leftside
Swelling2years Expansive radiolucentlesion with ‘‘Soapbubbles’’ aspect Myxoma Saitoetal.24 (1987) 52 F NR Frompremolar regiontomaxillary tuberosity,left side
Swelling 4years Osteolytic
multilocularlesion NR
Mustoeetal.25
(1984)
47 F Black Maxillarysinus,
leftside
Increaseof volume,painand headache NR Presenceof radiopaque scleroticmass withinthe maxillarysinus Orbital pseudotumor
Loh26(1984) 36 M Asian Lowercentral
incisorsregion
Swelling 1year Radiolucentlesion
withdefined marginscropped out Ameloblastoma Christensen etal.27(1987) 34 M NR Bodyofthe
mandible,leftside
Swelling 1year NR NR
RaleyandGranite
28(1977)
34 M Black Maxillary
tuberosity,right side
Swelling 1year Trabecularpattern
changed
NR
Lipperetal.29
(1975)
64 M White Mandible,leftside Swelling 6months Radiopaquemass Osteosarcoma
Webbetal.30
(1966)
Case1:59 Case1:F NR Case1:ramusand
angleofthe mandible,right side
Case1:pressure sensation
Case1:10months Case1:tumoral
mass NR
Case2:56 Case2:F Case2:ramusand
angleofthe mandible,right side
Case2:Swelling Case2:9months Case2:
Solitary plasmacytoma of the jaws: therapeutical considerations and prognosis 795
Table3 DetectionofM-protein(orparaprotein),therapeuticapproach,follow-uptime,recurrencesandevolutionforMM,aswellasfindingsconsideredrelevanttoeach article.
Reference Presenceof
M-protein
Treatment Followup Recurrences EvolutiontoMM Relevantfindings
Cioranuetal.13(2013) NR Chemotherapy,
Surgicalexcision and autotransplan-tation 2years/patient deceased No Previously diagnosedwithMM Recurrentlesions inotherbones; patient accompaniedby hematologistfor 14years
Anetal.14(2013) Positive Chemotherapy 8months No DiagnosedwithMM
throughalesionin themandible
Solitarylesion withsystemic signsofMM
Nandaetal.15(2012) Negative Partial
maxilectomy
1year No No Diagnosisof
extramedullary plasmacytoma Pintoetal.16(2007) Positive
(blood)/Negative (urine) Chemotherapy 9months/patient deceased No Yes DiagnosisofMM with plasmacytoma
Poggioetal.17(2007) Negative Radiotherapy 6months No No Patientwitha
historyofbone plasmocytomain thespine(12years ago)
Anil2(2007) Negative NR 5years No No
---Cangeretal.18(2007) Negative Patientdeceased
beforetreatment started 6months/patient deceased No No Patientsubmitted toprevious surgicalexcision ofplasmacytoma locatedintheiliac
Ozdemiretal.4(2005) Negative Chemotherapy NR NR No
---Yoonetal.19(2003) Negative Dosereductionof
immunosuppress-antsand radiotherapy
7years No No Patientunderwent
throughrenal
Matsumuraetal.20(2000) Positive Radiotherapye
chemotherapy
12months No No Thelesion
decreasedbutdid notdisappear
Hoetal.21(1999) Positive Radiotherapye
chemotherapy
28days No DiagnosedwithMM
throughalesionin themandible
Thelesion decreasedbutdid notdisappear
796 Lombardo EM et al. Table3(Continued) Reference Presenceof M-protein
Treatment Followup Recurrences EvolutiontoMM Relevantfindings
Millesietal.22(1997) Negative Radiotherapye
chemotherapye surgicalresection
4years No No Patientunderwent
through
reconstructionand oralrehabilitation
Kanazawaetal.23(1993) Positive Radiotherapyand
hemimandibulec-tomy
NR No No Patientunderwent
Saitoetal.24(1987) Positive Excisionalbiopsy
with1cmmargin
3yearsand6 months
Yes(1monthafter surgery)
No Recurrenceofthe
lesionwastreated witheffective radiotherapy
Mustoeetal.25(1984) Negative Radiotherapy NR No No
---Loh26(1984) Negative Surgicalexcision
andradiotherapy
3years No No
---Christensenetal.27(1987) NR Surgicalcurettage 3years Yes No Thecasereportis
focusedonthe recurrentlesion. Thetreatment wasradiotherapy. RaleyandGranite28(1977) Positive Surgicalexcision
andradiotherapy
NR No No
---Lipperetal.29(1975) Positive Hemimandibulectomy 9months No No
---Webbetal.30
(1966)
Case1:Negative Case1: Hemi-mandibulectomy
Case1:18 months/patient deceased
Case1:No Case1:Yes
---Case2:Negative Case2:Surgical curettageand radiotherapy
Solitaryplasmacytomaofthejaws:therapeuticalconsiderationsandprognosis 797 in8casereports,14,16,20,21,23,24,28,29correspondingto38.09%.
This rate is in the range of 24---72% indicated in other studies.5
ThepresenceofM-proteinisobtainedbyexaminationof electrophoresis frombloodor urine samples.33 The useof
thisexamtodeterminethediagnosisofSBPisstillinexact sincethepresenceofparaproteindoesnotalwaysdetermine theexistenceofthediseaseinquestion,however,itshould beemphasizedthatitsdiagnosticvalueisrelevantincases whereitisdesiredtoevaluatethepresenceofM-protein.1,34
There areauthors who advocatethat the presence of paraproteinevenaftertreatmentmaybeindicativeof resid-ualtumororhidden.1,35
Treatment
Thetreatmentusedforthecaseswerethefollowing: • Onlyradiotherapy---2cases.17,25
• Onlychemotherapy---3cases.4,14,16
• Onlysurgicalintervention---5cases.5,24,27,29,30
• Surgical intervention associated to radiotherapy --- 4 cases.23,26,28,30
• Radiotherapyassociatedtochemotherapy---2cases.20,21
• Surgicalintervention,radiotherapyand autotransplanta-tion---1case.13
• Radiotherapyanddecreaseddosageof immunosuppress-ors---1case.19
• Radiotherapy, chemotherapyandsurgical intervention ---1case.22
Inoneofthecasereportsthetherapeuticapproachwas notreported2andinanother,thepatientdeceasedbefore
startingtreatment.18Theidealtherapeuticapproachisstill
controversial,however,radiotherapyseemstobethe treat-mentthatoffersbetterclinicalresultssincetheSBPreveals itselfasaradiosensitivelesion.5,36 Therates oflocal
con-trol of SBP with radiotherapy presented in the literature exceedtherangeof80%.2,37,38Surgicalinterventionshould
becarriedoutinsituationswherethereisnopredictionof functionalorestheticdamage.23
Chemotherapyisadvocatedonlyonthebasisofreports intheliteraturethatshowedimprovementoflocalcontrol anddelayeddevelopmentofMM.38However,chemotherapy
alone hasno benefitcompared toradiotherapy but when institutedadjunctivelyitappearstoofferbeneficialeffect inpatientswithahigherriskoftreatmentfailure,thatis, thosewithtumorlesionsgreaterthan4---5cm.1,38,39
Prognosisandfollow-up
Follow-up timeafter treatment rangedfrom 28daysto 7 years.The meanfollow-upperiodwas19.9months.There were4deaths.13,16,18,19
Inonly2cases(9.5%)didSBPevolvetoMM.16,30Thelow
incidenceofprogressiontoMMin skullbonesdamagewas reportedinthesamewayinotherretrospectivestudies.23,26
Frequently, SBPcan be foundas aradiographic finding andcanrepresentaprimarylesionor focusofMMas pre-viouslyreported.40,41 Thepresent studyrevealed thatin 2
casereports,MMwasdiagnosedfromthedetectionofaskull bonelesion.14,21
There were 2 reports of recurrenceof the lesion, and inonecasetheeventoccurredin 1monthandinanother after3 years, both treated surgically.24,27 The mean time
torecurrenceof lesion aftertreatment reportedin other studieswas2---2.5years.42
The worst prognosis corresponds to progression from SBP to MM. Such event is directly related to the size of thetumors.Scientificevidencesuggeststhatpatientswho presenttumormasses,previouslydiagnosedasSBP,witha size larger than 4---5cm have a higher risk of developing MM.39 Inaddition,thebone locationof theplasmacytoma
incomparisonwiththeextramedullaryentity,age(patients over60years)andthepresenceofparaproteinatthetime of diagnosis also determine higher progression rates for
MM.36,43
Final
considerations
SBPisarareconditionin thebonesoftheface.Itaffects patients between the 4th and 6th decades of life with-outpredilectionforgender.Thelesionarisesmainlyinthe mandible,morepreciselyintheposteriorregion.Commonly, itpresents asa multilocularradiolucent lesion. The main signassociatedwiththedevelopmentofSBPispainless vol-umeincrease.Biopsy andhistopathologicexamination are mandatorysincethedefinitionofdiagnosisdeterminesthe needfor advancedinvestigationtoruleoutthepossibility ofMM.
Theimportanceofearlydiagnosisisjustifiedinthatthe plasmacytomamaybeaprimaryormetastaticlesionofMM. ThetreatmentofchoiceforSBPisradiotherapy.The associ-ationofsurgicalinterventionandchemotherapyisreserved forspecificcases.Periodicfollow-upofthepatientis neces-saryforatleast3yearsafterdiagnosisduetothepossibility ofdevelopingMM.
Conflicts
of
interest
Theauthorsdeclarenoconflictsofinterest.
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