Plasma Cell Dyscrasia (2)

8/17/2019 Plasma Cell Dyscrasia (2)

1/45

PLASMA CELL

NEOPLASMSDr. W.El Gendy

Prof of Clinical Pathology


2/45

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.


3/45


4/45

• 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.


5/45

• Osteosclerotic myeloma% POEMSsyndrome.


6/45

•

Diagnostic Criteria of each gro!p 'illdetermine the type.


7/45

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.


8/45

;. No e&idence of other )$cellproliferati&e disorder.


9/45

Plasma Cell Myeloma

• Diagnostic Criteria

2. Symptomatic plasma cell myeloma

•. M$protein in ser!m or !rine%


10/45


11/45


12/45


13/45

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


14/45

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.


15/45

• Stage ##

)et'een # 1 ###


16/45

• Stage ###

Any one or more of of the follo'ing

@igh M$protein #gG< g5dl% #gA


17/45

• S!*classi-cation *ased on renalf!nction

• A s. creatinine36mg5dl

• ) s. creatinine


18/45

#nternational staging system for

plasma cell myeloma

• Stage #

Ser!m *eta6$microglo*!lin34.;mg5dl

Ser!m al*!min


19/45

• Stage ###

Ser!m *eta6$microglo*!lin


20/45

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.


21/45

)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.


22/45

Genetic a*normalities inMyeloma

• #S@ increased detection to 78 ofcases.

• N!merical 1 str!ct!ral defects.

• +risomies% 'hole or partialchromosome deletions 1translocations.


23/45

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.


24/45

• a&o!ra*le ris0

A*sence of !nfa&o!ra*le ris0 genetics1 presence of hyperdiploidy% tF22=29or tF>=29 *y #S@.


25/45

#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.


26/45

• A*errant e"pression of CD22%CD67%CD;6%CD27.


27/45


28/45

• Erythroid prec!rsors can *e di:c!ltto di(erentiate.


29/45


30/45

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


31/45

Monoclonal #mm!noglo*!lin

Deposition Disease.

• Primary Amyloidosis

• Monoclonal light 1 hea&y chaindeposition diseases LCDD% L@CDD%@CDD.


32/45

Sites of in&ol&ement

• S!*c!taneo!s fat

• Iidney

•

@eart• Li&er

• G#+

•

Peripheral ner&es• )M


33/45

• )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


34/45

@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.


35/45

• 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 .


36/45

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.


37/45

• 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.


38/45

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


39/45

• 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.


40/45

• +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.


41/45

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 .


42/45

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


43/45

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.


44/45

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.


45/45

• 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

Plasma Cell Dyscrasia (2)

Documents

Transcript of Plasma Cell Dyscrasia (2)