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Multiple myeloma and bone

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Morphologie(2015)99,29—30

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EDITORIAL

Multiple myeloma and bone

Myélome multiple et os

Multiple myeloma(also called Kahler’s disease [MM]) is a hematological malignancy of Blymphocytes characterized by the expansionof a malignant plasma cellclone in the bonemarrow(Fig.1).Fivethousandcasesofmyelomaare diagnosed each year inFrance, 54% in men.In almost all cases, the malignant plasma cells secrete a monoclonal immunoglobulinoranimmunoglobulinfragment(freelight chain) which can be detected in the blood and/or urine.

This is currentlythe mostcommon wayof diagnosis after havingprescribedanelectrophoresis oranimmunofixation ofserumproteins.Indeed,MMisoftenprecededbyamono- clonal gammopathy of undetermined significance (MGUS), whichrequiresalongtermbiologicalmonitoring[1].MGUS are100timesmorecommonthanMM(andareobservedin 3—4%ofthepopulation after50years)andtheirevolution towardsanovertmyelomaisapproximately1%peryear.MM isahematologicalmalignancywhoseincidenceiscorrelated totheagingofthepopulation(themeanageatdiagnosisis about70years).

Myelomais themostcommonneoplasiaresponsiblefor osteolysisin90%ofpatients;itisresponsibleforfracturesin 60%ofcases[2,3].Bonelesionswereformerlythemostfre- quentlywayofrevelationofthediseaseandosteolysiscan summarizetheclinicalpresentation.The mosttypicalele- mentarylesionappearingonX-raysisa‘‘punched-out’’hole without peripheral condensation(Fig.2).The sizeis vari- ableandmultiplelocationsarecommon,primarilyaffecting the skull, spine, pelvis or rib cage. The bone lesion can lessfrequentlybeuniqueandlarge(plasmacytoma).Oste- olysisresults from an imbalancein bone remodelingwith increasedboneresorptionassociatedwithdecreasedbone formation. Malignant plasma cells areresponsible for the boneremodelingchanges.

Several recent reviews have been published showing the complexity of the cellularand molecular interactions occurring between plasma cells and the bone marrow microenvironmentcomposeofhematopoietic,vascularand bonecells[4].

Figure1 Noduleofmalignantplasmacellsdevelopedinthe bonemarrowofapatientwithmultiplemyeloma.

Nodule de plasmocytes tumoraux développé dans la moelle osseused’unpatientatteintdeMM.

InthisspecialissueofMorphology,itseemedimportant toustoprovideanupdate onthreetopicsthatarerarely discussedinrecentreviews:

• the morphology of the normal and pathological plasma cell during myeloma and MGUS is rarely reported.

The cytological aspectsare described in some classical atlases; Marc Zandecki and Bénédicte Ribourtout have extensivelydescribedthedifferentaspectsencountered onthebonemarrowaspirations.Theirworkistheresult ofalong experienceasacytologist concernedwiththe diagnosisofthesediseases;

• the myeloma bone eco-system is described by Régis BataillewhowasapioneerinFrancetodissectthecom- plexinteractionsbetweenthetumorplasmacellsandthe bonemarrowmicroenvironment.Thisarticlesummarizes http://dx.doi.org/10.1016/j.morpho.2015.04.001

1286-0115/©2015ElsevierMassonSAS.Allrightsreserved.

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30 Editorial

Figure2 TypicalX-rayimageoftheskullfromaMMpatient with‘‘punched-out’’holesreflectingpurelyosteolyticlesions.

Radiographieducrâned’unpatient atteint deMMmontrant l’aspect de lacunes osseuses à l’emporte-pièce traduisant l’aspectpurementostéolytiquedelatumeur.

theknowledgeonthequestion andopensnewperspec- tives in understanding the pathophysiology of MM and MGUS;

• animalmodelsofMMareapreclinicalapproachtosolve pathophysiologicalhypothesesandtestnewtherapeutics activeonthetumorcellitselfbutwhichcanalsospecif- ically target bone remodeling to disrupt the ‘‘vicious circle’’ between plasma cells and bone cells. Hélène Liboubanwroteanupdateonthecurrentanimalmodels

whicharealldevelopedinmice(MMcanalsobediagnosed occasionallyinhorsesanddogs).

WehopethatthisspecialissueofMorphologywillinterest allcytologists,histologists,radiologistsandoncologistswho followtheMMpatientseveryday.

Disclosure of interest

Theauthordeclaresthathehasnoconflictsofinterestcon- cerningthisarticle.

References

[1]Minter AR, SimpsonH, Weiss BM, Landgren O. Bone disease from monoclonal gammopathy of undetermined significance tomultiplemyeloma:pathogenesis,interventions,andfuture opportunities.SemHematol2011;48:55—65.

[2]RoodmanGD. Pathogenesisof myeloma bone disease. JCell Biochem2010;109:283—91.

[3]FowlerJA,EdwardsCM,CroucherPI.Tumor—hostcellinterac- tionsinthebonediseaseofmyeloma.Bone2011;48:121—8.

[4]Kuehl WM, Bergsagel PL. Molecular pathogenesis of multi- ple myeloma and its premalignant precursor. J Clin Invest 2012;122:3456.

D.Chappard Gerom:grouped’étudessurleremodelageosseuxetles

biomatériaux,IRIS-IBS,institutdebiologieensanté, CHUd’Angers,49933Angerscedex,France E-mailaddress:daniel.chappard@univ-angers.fr Availableonline4May2015

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