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rev bras hematol hemoter. 2016;38(2):166–169

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

Revista

Brasileira

de

Hematologia

e

Hemoterapia

Brazilian

Journal

of

Hematology

and

Hemotherapy

Case

Report

Bilateral

breast

plasmacytoma:

a

clinical

case

report

Thais

Rodrigues

da

Cunha

Fischer

,

Fabiana

Higashi,

Edvan

de

Queiroz

Crusoe,

Vania

Tietsche

de

Moraes

Hungria

FaculdadedeCiênciasMédicasdaSantaCasadeSãoPaulo(FCMSCSP),SãoPaulo,SP,Brazil

a

r

t

i

c

l

e

i

n

f

o

Articlehistory: Received3March2016 Accepted6March2016 Availableonline25March2016

Introduction

Theneoplasmofplasmacellsisagroupofdiseases encom-passing from monoclonal gammopathy of undetermined significance(MGUS)tomultiplemyeloma(MM).1

Conglomeratesofmonoclonalplasmacellsarecalled plas-macytomasandareincludedinthisgroup.2Theycanoccur

inisolationorassociatedwithMM,withthemostcommon locationbeingbonetissue.3

Theexistenceofextramedullaryplasmacytomashasalso beendescribed.Mostcommonly,theyaffectthehead,neck andsubcutaneoustissues,especiallyoftheupperrespiratory tract.4

Theyarepresentin7–19%ofpatientsatthetimeMMis diagnosed and in another 6–20% during the course ofthe disease.5

Breastplasmacytoma isarare condition.In2006,Taylor etal.,2described43casesintheliterature.Diagnosisismade

bypathologyhoweverimagingcanfurtheraidthediagnosis ofthedisease.Ultrasoundandmammographicaspectshave

Correspondingauthorat:RuaCapitãoMacedo,314/44,VilaMariana,04021020SãoPaulo,SP,Brazil.

E-mailaddress:thaisfischer@hotmail.com(T.R.d.C.Fischer).

already beendescribed intheliterature,ashaveaspectsof magneticresonanceimaging.2–4AcaseofMMwithmammary

glandinvolvementatdiagnosisisdescribedherein.

Case

report

A 52-year-old, Black female patient was admitted to hos-pital withasthenia. She had suffered 10kg ofweight loss, paininthethoracicregionandvomiting.Thephysical exam-ination showed pain on palpating the chest and bilateral breast lumps.Initialtestsshowedbicytopenia (anemiaand thrombocytopenia), renal dysfunction, and hypercalcemia. First, the symptomatic hypercalcemia was controlled and, subsequently,aninvestigationinto theetiologywascarried out, with mammary neoplasm being the initial hypothe-sis.Mammographyshowedhyperdensenodules,withregular marginsandlobulatedcontours,distributedbilaterally(Breast Imaging-Reportingand Data System –BI-RADS0), whereas ultrasonographyshowedmultiplesolidoval-shapednodules with lobulated contours and with vascularization by color

http://dx.doi.org/10.1016/j.bjhh.2016.03.003

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rev bras hematol hemoter. 2016;38(2):166–169

167

Figure1–(AandB)Mammography:hyperdenseandlobulatednoduleswithcircumscribedmargins;(C)extra-axial expansivelesioncompatiblewithplasmocytomaintherightfrontalconvexity(arrow)withpachymeningealimpregnation (arrowhead),demonstratingcentralnervoussysteminvolvement;(D)spectroscopyofthesamepatientshowingan increasedglutamine–glutamatecomplex(arrow)resultingfromelevatedcentralnervoussystemammonia.

Doppler(Figure1).Acorebiopsywasperformed.Testresults, however, ruled out primary breast cancer while showing breastplasmacytoma,withlambdachainrestriction,plasma cell ratio of95%,CD138+ and negative forCD56(Figure 2). OthertestsconductedtoconfirmMMwerepositive.Protein electrophoresisidentifiedmonoclonalcomponents(5.34g/dL), immunofixation identified IgA/Lambda and bone marrow biopsyshowedbonemarrowplasmacytosis90%,CD138+,and Lambda+ (Figure 2). Hence, a diagnosis ofIgA/lambda MM withextramedullaryplasmacytomalocatedinthebreastwas reached,withaninternationalstagingsystemscoreofIIIand DurieSalmon(DS)stageofIIIB.

The patient underwent induction chemotherapy with theadministrationoftheCTDregimen(cyclophosphamide, thalidomide,anddexamethasone).Afterthreecycles,her clin-icalconditionworsenedwithalteredlevelofconsciousness, seizures, and disease progression with new plasmacy-tomas (sternum and central nervous system−CNS) and

hyperammonemia being observed. This metabolic change

was established by measuring the serum ammonia level (93␮mol/L; normal value up to 32␮mol/L) and confirmed by proton magneticresonance spectroscopy (PMRS), which showedaglutamine/glutamatepeakandreducedcholineand myo-inositol(Figure1).

The chemotherapy regimen was then changed to a combination of dexamethasone, thalidomide, doxorubicin, cisplatin,cyclophosphamide,andetoposide(DT-PACE).After three cycles of this chemotherapeutic regimen, the mono-colonal component reduced completely and there was a reductionintheextramedullaryplasmacytomas(breast, ster-num, and CNS).Treatment then proceededwithhigh-dose melphalanandrescuewithautologoushematopoietic progen-itorstem celltransplantation and subsequentradiotherapy againstthesternalplasmocytoma.

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rev bras hematol hemoter. 2016;38(2):166–169

Figure2–(A)Breastand(B)bonemarrowbiopsies,bothwithhematoxylinandeosin(HE)stainingcharacterizedby

infiltrationofplasmacells;Breastbiopsyimmunochemistrywith(C)lambdarestrictionand(D)CD138+immunoexpression.

intrathecal chemotherapy (methotrexate, cytarabine, and dexamethasone).

She evolved to death ten months after diagnosis, with multiple extramedullary plasmacytomas (breast, sternum, CNS,subcutaneoustissue)and absence ofany monoclonal component.

Discussion

Extramedullary plasmacytomasofthe breast are rare;they havebeenfoundatdiagnosisinonly14%ofcases.Most(75%) plasmacytomasofthebreastoccurduringrelapseofMM.2

Theepidemiologicalcharacteristicsofthecasedescribed hereinareconsistentwiththedataintheliterature,regarding genderandage.Mostbreastplasmocytomasoccurinwomen withameanageof53yearsatdiagnosis,butpredominantly unilateral.2,3

Themammographicresultsofthis patientare in agree-ment with the findings reported in the literature as well-defined masses with irregular margins. On the other hand,theultrasonographic patterndescribed byauthors is heterogeneous, with hyperechoic, hypoechoic, or anechoic lesionsbeingreported.3

The prognosis of patients with extramedullary plasma-cytoma is variable. Solitary plasmacytomas have a good prognosis (radiotherapyand surgeryarecurative treatment options)andlessthan30%ofcasesdevelopMMorother plas-macytomas,whereasthediseaseprogresseswithunfavorable outcomesinpatientswithMMandextramedullaryprimaryor secondaryplasmacytomas,asinthiscase.5

Progressionofthediseasewasobservedinthecurrentcase withnewextramedullaryplasmacytomasdespiteoftheCTD regimen. Using PMRSand determinationof serum ammo-nialevels,hyperammonemicencephalopathywasalsofound. ThisconditiontogetherwithMMandwithoutliverdiseaseis rare(3.8%).Nevertheless,itshouldbeconsideredinpatients with altered levels of consciousness, as observed in this patient.6,7

Hyperammonemiawasnotconsideredastheonlysingle factor forthe alteredmental status,but part ofacomplex scenario, which included hyperviscosity of the blood, CNS infiltration,andhypercalcemia.

Thisencephalopathyiscausedbytheproductionof ammo-niaatcriticallevelsbytheplasmacellsthemselves,thereby exceedingthedepurationcapacityofhepatocytes.8

InthesystematicreviewbyPhametal.,6

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rev bras hematol hemoter. 2016;38(2):166–169

169

subtypesIgAandIgG,advancedstagesofthedisease,andCNS infiltration,whichleadstoaworseprognosiswithhigherrates ofhospitalizationandmortality.9,10

Considering the progression and aggressiveness of the disease,thechoicewastomodifytreatmenttotheDT-PACE regimen.11 Bladè et al.12 found that extramedullary

dis-ease appears to be more properly treated with intensive chemotherapy regimens, including new agents such as lenalidomide and pomalidomide, compared to traditional therapiesforMM;however,thisoptionisnotclearlydescribed intheliteratureyet.

Extramedullarydisease,whetherthepatienthas plasma-cytomasoftheboneornot,maybethemostimportantclinical findinginthecourseofMM,asinthis case.Thebiological mechanismsunderlyingthisoccurrencehavenotbeen prop-erlyestablished,butaseriesofeventsarepostulated.These includingdecreasedexpressionofadhesionmolecules(CD44 andCD56),increasedangiogenesis,lossofcytokinereceptors responsibleforplasmacellhoming[C-X-Cchemokine recep-tortype4(CXCR4)andC-X-Cmotifchemokine12(CXCL12)] andbonemarrowhypoxemia,causingthesecellstomigrateto theperiphery.AlthoughthelossofCD56expressionfacilitates hematogenousorbonedissemination,itsexpressionis para-doxicallyassociatedwithimpairmentofspecificsites,suchas

theCNS.13,14

The heterogeneity in CD56 marking could be duly evidencedinthiscase,wheretherewaslossofCD56 expres-sion in the plasmocytoma of the breast and, during the patient’sprogression,thismarkerwasshowntobepositive whenimmunophenotypingtheliquor;thissuggeststhe influ-enceofasyetunknownmechanismsandotherfactors.

Althoughcytogenetics assays were not carriedout, this does not seem to be a finding capable of predicting out-comes.Vargaetal.,15inastudyof117patients,demonstrated

that unfavorable cytogenetics results at diagnosis did not determinetheoccurrenceofextramedullarydiseaseorpoor prognosis.

Theclinicalcharacteristics andlaboratoryresultsofthis patient were already indicative of a poor prognosis with lowchances ofsurvivalatdiagnosis (ISS: III). Her progres-sion with extramedullary plasmocytomas, probably due to hematogenousdissemination,onlycorroboratedthe biolog-ical complexity of the disease. The median survival time reportedforthesecasesistenmonthsinspiteofthetreatment administered,aswasseeninthiscase.13,15

Conflict

of

interest

Theauthorsdeclarenoconflictsofinterest.

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1.HuberH,HohnMJ,RachelR,FuchsT,WimmerVC,StetterKO.

AnewphylumofArchaearepresentedbyananosized

hyperthermophilicsymbiont.Nature.2002;417(6884):63–7.

2.TaylorL,AzizM,KleinP,JagannathS,AxelrodD.

Plasmacytomainthebreastwithaxillarylymphnode

involvement:acasereport.ClinlBreastCancer.2006;7(1):81–4.

3.BremRF,RevelonG,WilleySC,GatewoodOM,ZeigerMA.

Bilateralplasmacytomaofthebreast:acasereport.BreastJ.

2002;8(6):393–5.

4.LamyO,vonBremenK,BurckhardtP.Breastplasmacytoma.

LeukLymphoma.2000;37(5-6):611–5.

5.UsmaniSZ,HeuckC,MitchellA,SzymonifkaJ,NairB,Hoering

A,etal.Extramedullarydiseaseportendspoorprognosisin

multiplemyelomaandisover-representedinhigh-risk

diseaseevenintheeraofnovelagents.Haematologica.

2012;97(11):1761–7.

6.PhamA,ReaganJL,CastilloJJ.Multiplemyeloma-induced

hyperammonemicencephalopathy:anentityassociatedwith

highin-patientmortality.LeukRes.2013;37(10):1229–32.

7.TalamoG,CavalloF,ZangariM,BarlogieB,LeeCK,

Pineda-RomanM,etal.Hyperammonemiaand

encephalopathyinpatientswithmultiplemyeloma.AmJ

Hematol.2007;82(6):414–5.

8.OtsukiT,YamadaO,SakaguchiH,IchikiT,KouguchiK,Wada

H,etal.Invitroexcessammoniaproductioninhuman

myelomacelllines.Leukemia.1998;12(7):1149–58.

9.FassasAB,MuwallaF,BerrymanT,BenramdaneR,JosephL,

AnaissieE,etal.Myelomaofthecentralnervoussystem:

associationwithhigh-riskchromosomalabnormalities,

plasmablasticmorphologyandextramedullary

manifestations.BritJHaematol.2002;117(1):103–8.

10.KyleRA,GertzMA,WitzigTE,LustJA,LacyMQ,DispenzieriA,

etal.Reviewof1027patientswithnewlydiagnosedmultiple

myeloma.MayoClinProc.2003;78(1):21–33.

11.LeeCK,BarlogieB,MunshiN,ZangariM,FassasA,JacobsonJ,

etal.DTPACE:aneffective,novelcombinationchemotherapy

withthalidomideforpreviouslytreatedpatientswith

myeloma.JClinOncol.2003;21(15):2732–9.

12.BladéJ,FernandezdeLarreaC,RosinolL.Extramedullary

diseaseinmultiplemyelomaintheeraofnovelagents.BritJ

Haematol.2015;169(6):763–5.

13.BladéJ,FernándezdeLarreaC,Rosi ˜nolL,CibeiraMT,Jiménez

R,PowlesR.Soft-tissueplasmacytomasinmultiplemyeloma:

incidence,mechanismsofextramedullaryspread,and

treatmentapproach.JClinOncol.2011;29(28):3805–12.

14.GangatharanSA,CarneyDA,PrinceHM,WolfMM,

JanuszewiczEH,RitchieDS,etal.Emergenceofcentral

nervoussystemmyelomaintheeraofnovelagents.Hematol

Oncol.2012;30(4):170–4.

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WeinstockM,etal.Developmentofextramedullarymyeloma

intheeraofnovelagents:noevidenceofincreasedriskwith

lenalidomide–bortezomibcombinations.BritJHaematol.

Imagem

Figure 1 – (A and B) Mammography: hyperdense and lobulated nodules with circumscribed margins; (C) extra-axial expansive lesion compatible with plasmocytoma in the right frontal convexity (arrow) with pachymeningeal impregnation (arrowhead), demonstrating
Figure 2 – (A) Breast and (B) bone marrow biopsies, both with hematoxylin and eosin (HE) staining characterized by

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