Rev. Bras. Hematol. Hemoter. vol.39 número1

rev bras hematol hemoter. 2017;39(1):66–69

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

Revista

Brasileira

de

Hematologia

e

Hemoterapia

Brazilian

Journal

of

Hematology

and

Hemotherapy

Case

report

Plasma

cell

leukemia

with

t(11;14)(q13;q32)

simulating

lymphoplasmacytic

lymphoma

–

a

diagnostic

challenge

solved

by

flow

cytometry

Aleyde

Diniz

Loureiro

_,

_Matheus

_Vescovi

_Gonc¸alves

_,

_Maura

_Rosário

_Valério

_Ikoma

_,

Maria

Regina

Regis

Silva

_,

_Gisele

_Wally

_Braga

_Colleoni

_,

_Maria

_de

_Lourdes

_Chauffaille

_,

Mihoko

Yamamoto

a_{UniversidadeFederaldeSãoPaulo(UNIFESP),SãoPaulo,SP,Brazil}

b_{Fundac¸ãoAmaralCarvalho,Jau,SP,Brazil}

a

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Articlehistory:

Received6September2016 Accepted10October2016 Availableonline22December2016

Introduction

Plasmacellleukemia(PCL)isarareandaggressive manifes-tationofmalignantplasmacellproliferationandcorresponds to2–4%ofmultiplemyeloma(MM)cases.1,2_{TheWorldHealth} Organization(WHO)definesPCLbythepresenceofhighlevels (atleast2×109/L)ofclonalplasmacellsintheperipheralblood (PB)oratleast20%oftheleukocytedifferentialcount.1 Pri-maryPCL(pPCL)correspondsto60%ofthecasesandpresents as leukemia at diagnosis, usually with tissue infiltration, organomegalyandlymphadenopathyandalowerfrequency ofbonelesions(15–40%cases)thanmultiplemyeloma.2 Sec-ondaryPCListheterminalphaseofMMandcorrespondsto theremaining40%ofPCLcases;itusuallyhasapoorresponse tostandard MMtreatment.2,3 _{The diagnosis ofplasmacell} neoplasmsiseasilysuggestedbythecharacteristicplasmacell

∗ _{Correspondingauthorat:DisciplinadeHematologiaeHemoterapia,EscolaPaulistadeMedicina(EPM),UniversidadeFederaldeSão}

Paulo(UNIFESP),RuaDr.DiogodeFaria,824,3◦_{Andar,04037-003SãoPaulo,SP,Brazil.}

E-mailaddress:yamamoto@unifesp.br(M.Yamamoto).

morphology,bothinMMandinPCL.Thegreatcontributionof immunophenotypingbyflowcytometry(FC)insuchdisorders depends on differentiatingnormal from neoplastic plasma cells.4,5_{However,inrarecasesofMMwithatypical} morphol-ogythedifferentialdiagnosiswithotherlymphoproliferative disordersmaybeachallenge.Here,wepresentacaseofpPCL inwhichthediagnosisoflymphoplasmacyticlymphoma(LPL) wasinitiallysuggestedbymorphologyofperipheralblood(PB) andbonemarrow(BM)cells(aspirateandbiopsy)withthefinal diagnosisofpPCLbeingestablishedbyFC.

Case

report

A 77-year-old female patient consulted in the Rheuma-tology Service of the Hospital São Paulo for osteoporosis and was referred to the Hematology Clinic to investigate

http://dx.doi.org/10.1016/j.bjhh.2016.10.001

rev bras hematol hemoter. 2017;39(1):66–69

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Figure1–Neoplasticcellmorphologyinperipheralblood(A)andbonemarrowaspiratefilms(B)showingsmall-to medium-sizedlymphoplasmacyticlymphocytes(MayGrunwaldGiemsastain,1000×).Bonemarrowbiopsy(C)replacedby

medium-sizedlymphocytes(C1;Hematoxylinandeosin _{stain,400×)andimmunohistochemistryexpressionofKi67of} tumorcells(C2;immunoperoxidase,400×).

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Figure2–Flowcytometrydotplotsofthecirculatingplasmacells(inblackdots)showingsmall-tolarge-sizedclonal plasmacellsexpressing(forward/sidescatteroflight)CD45−_,CD19/CD20−_,CD38++_/CD138+_{heterogeneousand}

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Figure3–FISHusingprobesfortheCCND1 _gene(red)and IGH _{gene(green),andredandgreenfusion,corresponding}

toIGH-CCND1 rearrangement.

anemia. At physical examination, she was in good gen-eral condition without palpable lymph nodes, or liver or spleen enlargement. The complete blood count showed: Hemoglobin=10.1g/dL; Hematocrit=32.4%;white blood cell count8.6×109/L (neutrophils: 37%; lymphocytes: 58%) and platelet count140×109/L.Morphological analysisofthePB smearshowedsmall-tomoderate-sizedlymphoplasmacytoid lymphocytes(75%ofthelymphocytes)withbasophilic cyto-plasmand 1to 2nucleoli(Figure1A). BMaspirateshowed 90%oflymphocyteswiththesamecharacteristicsand5.6% oftypicalplasmacells(Figure1B).BMbiopsyshowed hyper-cellularmarrowwith80%ofyoung,small-tomedium-sized lymphoid cells (Figure1C). BMimmunohistochemistrywas inconclusive: tumor cells were negative for all of the fol-lowingantigens:CD45, CD3,CD5,CD10,CD20, CD23,CD30, CD79a,CD138,PAX5,CD1A,CD56,TdT,kappa,lambdaand cyclin D1, but the Ki67 was positivein about 40% ofcells. Theother laboratorialtestsshowedtotalserumproteinsof 10.2g/dL,albuminof3.83g/dL and monoclonalpeakinthe gamma globulinregion(4.4g/dL) thatwas identifiedasIgG byimmunofixation;normaltotalserumCa(10.8mg/dL)with ionic Ca 1.45mM/L (normal 1.15–1.32mM/L) and increased beta-2 microglobulin(4.7mg/L).Lytic lesions were seen on skullX-ray.Immunophenotyping byFCofBMcellsshowed thepresenceofclonalplasmacells (40%)expressing CD38, CD138dim_{, cykappa, smkappa, ␤-2microglobulin and CD81,} and were negative forCD45, CD56, CD19, cylambda, CD28 andCD117,suggestingaplasmacellmalignancydespitethe morphologicfeaturesofLPL(Figure2).SmallBlymphocytes (1.17%)expressedthenormalBcellphenotype(CD45++_,CD 19+_,CD20++_,CD79b+_,CD24+_,FMC-7+_,smKappa+_/smLambda+ ratio of2:1, and negativeforthe CD5, CD10, CD11c, CD23, CD200,CD38,CD43antigens).Thefinal diagnosis wasPCL, IgG kappa. A fluorescent in situ hybridization (FISH) study waspositiveforcyclinD1(PRAD1,CCND1)/IGHrearrangement, showingthepresenceoft(11;14)(q13;q32)(Figure3). Consid-eringthe age ofthe patient(>70 years old)and transplant ineligibility,thetreatmentoptionwasmelphalan,thalidomide anddexamethasone.However,thepatientevolvedwith wors-eningofperformancestatusandgastricdiscomfortandshe

decidedtostopthethalidomide.Duetotheworseningofher clinicalcondition,itwasdecidedtouseonlydexamethasone (40mg/week)andclosemonitoringofherclinicalcondition. Afterthreemonths,thepatientsufferedapathologicalfemur fractureandeventuallydiedofpulmonarysepsis.

Discussion

pPCLisararediseasethataffectsyoungerindividuals;ithas asubacuteonsetandpatientshaveapoorerperformance sta-tus(ISS3inabout60%ofcases)atdiagnosisthanthosewith MM.1,2,6 _{Thereisahigh incidenceofanemiaand} thrombo-cytopenia duetothe suppressionofnormalhematopoiesis intheBMwhichisusuallygreatlyinfiltrated.2,4,6_Moreover, pPCLhasahigherincidenceofextramedullaryinvolvement that appears to be a result of a lower expression of cell adhesion molecules, such as CD56, facilitating the release ofleukemicplasmacellsfromtheBMmicroenvironment.4,5 Our patient had no evidence of extramedullary disease at diagnosis, but she presented mild anemia and was under treatment for osteoporosis. Her BM biopsy showed exten-siveinvolvementbylymphoplasmacytoidcellsthathadthe same characteristics asinthe PB,which sometimesmakes the differential diagnosis between LPL and PCLdifficultby morphological analysis alone. Immunohistochemistry was inconclusiveas,unexpectedly,theexpressionofCD138was negativeinneoplasticcells.Thereasonsforthismaybedue todown-regulationoftheantigenorthesamplepreparation process.Inthis particularcase,FChadakey rolein estab-lishing the correctdiagnosis.4,5,7,8 _{Normal plasma cells are} CD19+_/CD45+_/CD38bright_/CD56−_{whileneoplasticplasmacells} are usuallyCD19−_/CD45−_/CD38+_/CD56+_.5,8 _{However,asseen} inthepresentcase,PCLcells showalowexpressionofthe cell adhesionmoleculeCD56suggestingaworseprognosis; thiswasassociatedwiththepresenceofneoplasticcellsin thePB.4,9_{LPLismorphologicallycharacterizedbythepresence} ofsmallplasmacytoidlymphocytesandsomeplasmacellsin whichtheimmunophenotypeusuallyresemblesthenormal lymphocytes and plasma cells exceptfor clonalrestriction andCD25+/− _andCD138+/−_{expression.Thisdiffersfromthe} immunophenotypeprofileofneoplasticplasmacellsfoundin thiscase.1,7,8,10

Furthermore, FC can also give additional information relatedtotheprognosisinplasmacellneoplasms.The expres-sions of B2 microglobulin and CD81, both positive in the currentcase,andtheabsenceofCD45arerelatedtoanadverse prognosis.5,11 _{Expression of CD28represents an aggressive} phenotype associated with tumor expansion and shorter disease free survival.5 _{In our patient, the malignant cells} expressedanunfavorableimmunophenotypicprofileexcept fortheabsenceofCD28.Plasmacells,eithernormalor malig-nant,usuallyexpressCD138,butmalignantplasmacellsmay have dim expressionofthis marker, which maybe dueto down-regulationofthisantigen.Importantly,thecytogenetic alterationdetectedinthiscaseisdescribedinapproximately 20%ofallplasmacellneoplasms.2,3_{Thepresenceoft(11;14)} (q13;q32) reflects the juxtaposition of the proto-oncogene

rev bras hematol hemoter. 2017;39(1):66–69

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overallsurvival.2,12 _{However,theexpectedoverexpressionof} cyclin D1 was not identified in the BM biopsy specimen, probablyduetoantigenretrieval problemsafterthe decal-cification ofthe sample. Additionally, the presence ofthis abnormalityinplasmacellneoplasmsisusuallyassociated withtheatypicalmorphologicappearanceofLPLreportedin 50%ofthecases.6_{Furthermore,lackofexpressionsofCD56} andCD117havebeenassociatedtoplasmacellmalignancies inpatientswitht(11;14), aspreviouslydescribed.9 _Of inter-est,theMYD88L265Psomaticmutation,presentin>90%of patientswithLPL/Waldenström’smacroglobulinemiaandalso innon-IgMLPL,isusefultodifferentiatethesedisordersfrom MM,includingIgMsecretingmyeloma,andsomeotherB-cell malignancies.13_{Thisstudywasnotcarriedoutinthepresent} casebecausethediagnosisofPCLwasquicklyconcludedby FC.Inconclusion,thepresentclinicalcaseillustratestherare presentationofPCLwithatypicalmorphologyandhighlights theimportance ofFCinthe differential diagnosis between PCLandLPL.Additionallyt(11;14)(q13;q32)byFISH,increased theinformationnotonlyaboutthediagnosis butaboutthe prognosis.

Conflict

of

interest

Theauthorsdeclarenoconflictofinterest.

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