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PLASMA CELL
NEOPLASMSDr. W.El Gendy
Prof of Clinical Pathology
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Plasma Cell Neoplasms
• es!lt from the e"pansion of a clone of #g$secreting%
• hea&y$chain class s'itched%
• terminally di(erentiated ) cell• that typically secrete a single
homogeneo!s% monoclonal% imm!noglo*!lincalled paraprotein or M$*and.
• +he presence of s!ch protein is calledmonoclonal gammopathy.
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• Plasmacytoma
Solitary plasmacytoma of *ones
E"traosseo!s% e"tramed!llary%myeloma
• #mm!noglo*!lin deposition disease
Primary Amyloidosis Systemic light 1 hea&y chain
deposition diseases.
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• Osteosclerotic myeloma% POEMSsyndrome.
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•
Diagnostic Criteria of each gro!p 'illdetermine the type.
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MG,S
• Diagnostic criteria
2. M$protein in ser!m 3 4 gm5dl
6. )M clonal plasma cells 3 278 1 lo')M in-ltration in trephine *iopsy.
4. No lytic *one lesions.
9. No myeloma$related organ or tiss!eimpairment% CA) hypercalcemia%renal ins!:ciency% anemia% *onelesions.
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;. No e&idence of other )$cellproliferati&e disorder.
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Plasma Cell Myeloma
• Diagnostic Criteria
2. Symptomatic plasma cell myeloma
•. M$protein in ser!m or !rine%
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Plasma Cell Le!0emia
• N!m*er of clonal plasma cells inperipheral *lood e"ceeds 67775cmmor is 678 of di(erential W)C co!nt.
• Primary PCL -rst presentation.
• Secondary PCL late in a case ofPlasma Cell Myeloma.
• Lac0 of e"pression of a*errant CD;>is typical for PCL di(ering it fromother myelomas
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Myeloma Staging System.
• Stage #
Lo' M$protein le&els% #gG3; g5dl%#gA34g5dl%!rine *ence
?ones39g569hr.
A*sent or solitary *one lesion
Normal @*% Calci!m% #gs non$M protein.
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• Stage ##
)et'een # 1 ###
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• Stage ###
Any one or more of of the follo'ing
@igh M$protein #gG< g5dl% #gA
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• S!*classi-cation *ased on renalf!nction
• A s. creatinine36mg5dl
• ) s. creatinine
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#nternational staging system for
plasma cell myeloma
• Stage #
Ser!m *eta6$microglo*!lin34.;mg5dl
Ser!m al*!min
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• Stage ###
Ser!m *eta6$microglo*!lin
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Peripheral )lood
• o!lea!" formation is !s!ally themost stri0ing feat!re on P) smears 1is related to the !antity 1 type of M$
protein.
• A le!0oerythro*lastic reaction can *eseen in some cases.
• Plasma cells are seen inappro"imately 2;8 of cases in smalln!m*ers.
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)M )iopsy
• #n contrast to normal plasma cells % 'hichare typically fo!nd in small cl!stersaro!nd )M arterioles% myeloma plasma
cells !s!ally occ!r in interstitial cl!sters %focal nod!les or di(!se sheets.Generally% 'hen 478 of the )M &ol!me iscomprised of plasma cells % a diagnosis of
myeloma is li0ely% altho!gh rare cases ofreacti&e plasmacytosis may reach thatle&el.
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Genetic a*normalities inMyeloma
• #S@ increased detection to 78 ofcases.
• N!merical 1 str!ct!ral defects.
• +risomies% 'hole or partialchromosome deletions 1translocations.
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Cytogenetic prognostic gro!ps inPlasma Cell Myeloma
• ,nfa&o!a*le ris0
Deletion 24 or ane!ploidy *ymetaphase analysisFcon&entionalcytogenetics.
tF9=29 or tF29=2> or tF29=67 *y #S@.
Deletion 2p24 *y #S@.
@ypodiploidy.
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• a&o!ra*le ris0
A*sence of !nfa&o!ra*le ris0 genetics1 presence of hyperdiploidy% tF22=29or tF>=29 *y #S@.
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#mm!nophenotyping.
• Plasma Cell Myeloma
CD24B H
Strong CD4B H
CDa H
Similar to normal plasma cells
#n contrast to normal plasma cells
Al'ays CD2 negati&eA*errant e"pression of CD;> in 7$B78 of
cases.
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• A*errant e"pression of CD22%CD67%CD;6%CD27.
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• Erythroid prec!rsors can *e di:c!ltto di(erentiate.
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Monoclonal #mm!noglo*!lin
Deposition Diseases M#DD.
• /isceral 1 soft tiss!e deposition of#gs leading to compromised organf!nction.
• ,nderlying ca!se is plasma cellneoplasm or rarelylymphoplasmocytic neoplasm
• #gs acc!m!late early *efore o&ertplasma cell myeloma% so at time ofdiagnosis they do not sho' plasma
cell neoplasm or lymphoplasmocytic
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Monoclonal #mm!noglo*!lin
Deposition Disease.
• Primary Amyloidosis
• Monoclonal light 1 hea&y chaindeposition diseases LCDD% L@CDD%@CDD.
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Sites of in&ol&ement
• S!*c!taneo!s fat
• Iidney
•
@eart• Li&er
• G#+
•
Peripheral ner&es• )M
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• )M *iopsy sections can re&ealreplacement of )M tiss!e *y Amyloid
• @E section appearance pin0%amorpho!s% 'a"y
• Aro!nd )lood &essels
• A*dominal fat
• )M
• Congo red staining is diagnostic
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@ea&y chain diseases
• +he hea&y chain diseases F@CD comprise 4 rare) cell neoplasms that prod!ce monoclonal hea&ychains 1 typically no light chains.
• +he monoclonal imm!noglo*!lin component is
composed of either #gG F gamma @CD . #gAFalpha @CD or #gM Fm! @CD % +he hea&y chain is!s!ally incomplete and th!s incapa*le of f!llassem*ly. /aria*ly siJed proteins are prod!ced %
that may not prod!ce a characteristic ser!mprotein electrophoresis pea0 and re!ire imm!no$electrophoresis or imm!no$-"ation to detect.
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• Alpha @CD is considered to *e a &ariant ofe"tra nodal marginal Jone lymphoma ofm!cosa associated lymphoid tiss!e FMAL+.
• Gamma @CD is characteriJed *y alymphoplasmacytic pop!lation resem*ling#ymphoplasmacytic lymphoma
• M! @CD typically resem*les CLL ho'e&er
*oth are s!:ciently distincti&e to *econsidered separate entities .
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Gamma hea&y chaindisease
• +he P) may sho' lymphocytosis 'ith or'ith$o!t plasmacytoid lymphocytesresem*ling chronic lymphocytic
le!0aemia FCLL a #ymphoplasmacyticlymphoma. +ransformation to di(!selarge ) $cell lymphomaFDL)Cl is rare. +he)M may sho' #ympho$plasmacytic
aggregates or only a s!*tle increase inplasma cells 'ith monotypic gammahea&y chains 'itho!t light chains.
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• A*normal 0aryotypes ha&e *eenpresent in a*o!t half of the reportedcases *!t no speci-c or rec!rring
genetic a*normality has *eenreported.
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M! hea&y chain disease.
• M! hea&y chain d isease Fm! @CD is a ) cell neoplasm resem*lingchronic #ymphocytic le!0aemia FCLL
in 'hich a defecti&e m! hea&y chainlac0ing a &aria*le region is prod!ced.
+he )M contains an in-ltrate of
characteristic &ac!olated plasmacells% admi"ed 'ith small % ro!ndlymphocytes
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• A slo'ly progressi&e disease resem*ling CLL.
M! @CD di(ers from most cases of CLL in
• high fre!ency of hepatosplenomegaly and
• a*sence of peripheral lymphadenopathy.
• o!tine ser!m protein electrophoresis is fre!ently normal.• #mm!no$electrophoresis re&eals reacti&ity to anti$m! in
polymers of di&erse siJes. Altho!gh m!$chain is not fo!nd inthe !rine% )ence$ Kones light chains are commonly fo!ndF;78 in the !rine% partic!larly 0appa chains . +he latter
'hile still prod!ced in m! @CD % are not assem*led in to acomplete imm!noglo*!lin protein *eca!se of hea&y chaingene a*errancies leading to tr!ncated forms.
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• +he )M contains &ac!olated plasmacells 'hich are typically admi"ed'ith small ro!nd lymphocytes similar
to CLL.• E"press )$cell antigens 1 are CD;%
CD27 negati&e.
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Alpha hea&y chain disease
• +he term imm!noproliferati&e small intestinaldisease F #PS#D 'as adopted *y the W@O in 2B.
• PS#D is a &ariant of e"tranodal marginal Jonelymphoma of m!cosa associated lymphoid tiss!e
FMAL+% in 'hich defecti&e alpha hea&y chains aresecreted.
• #t occ!rs in yo!ng ad!lts and in&ol&es thegastrointestinal tract % res!lting in mal$a*sorptionand diarrhoea . #PS#D *egins as a process sometimesre&ersi*le *y anti*iotics *!t may progress to di(!selarge ) $cell lymphoma FDL)CL .
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POEMSOS+EOSCLEO+#C MELOMA
CharacteriJed *y
• i*rosis
• Osteosclerotic changes in *one tra*ec!lae
• LN changes• Polyne!ropathy
• Organomegaly
• Endocrinopathy• Monoclonal gammopathy
• S0in changes
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Morphology.
• Osteosclerotic plasmacytoma% singleor m!ltiple
• As focally thic0ened tra*ec!lar *one
'ith closely associatedparatra*ec!lar -*rosis 'ithentrapped plasma cells% 'hich may
appear elongated d!e to -*rosis.
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Waldenstrms Macroglo*!linemia.
• +he de-nition of WM and its relationship to LPL ha&e *eenpro*lematic.
• +he 677B classi-cation adopted the approach of the second#nternational Wor0shop on Waldenstrms Macroglo*!linemia%
'hich de-ned WM as the presence of an #gM monoclonal
gammopathy of any concentration associated 'ith )M in&ol&ement *y LPL.
• +herefore% LPL and WM are not synonymo!s% 'ith WM no'de-ned as a s!*set of LPL.
• +he presence of e&en a large #gM paraprotein in the a*sence
of a LPL is no longer considered WM% and LPL in the a*sencean #gM paraprotein is not WM.
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• Waldenstrom macroglo*!linemiaFWMis fo!nd in a signi-cant s!*setof patients 'ith LPL and is de-ned as
LPL 'ith )M in&ol&ement and an #gMmonoclonal gammopathy of anyconcentration