linfoma di hodgkin - unibo. linfoma di hodgkin. thomas hodgkin circa 1835 born 1798 pentonville,

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Linfoma di HodgkinLinfoma di Hodgkin

Thomas HodgkinThomas Hodgkin circa 1835circa 1835born 1798 born 1798 PentonvillePentonville, , LondonLondonQuaker familyQuaker family1825 lecturer in morbid 1825 lecturer in morbid anatomy and curator of the anatomy and curator of the museum Guymuseum Guyssfellow members of stafffellow members of staff-- Richard BrightRichard Bright-- Thomas AddisonThomas Addison

The Man:The Man:

paper first read before thepaper first read before theMedicoMedico--ChirugicalChirugical Society of Society of London,London, January 10th 1832January 10th 1832

6 cases from Guy6 cases from Guys Museum s Museum and 1 from UCHand 1 from UCH

enlargement of the glands enlargement of the glands appeared to be a primitive appeared to be a primitive affection of those bodies, affection of those bodies, rather than the result rather than the result of an irritation... from some of an irritation... from some ulcerated surface or other ulcerated surface or other inflamed texture.inflamed texture.

The Disease:The Disease:

1926 Fox1926 Fox examined 3 cases examined 3 cases microscopically:microscopically:2 were Hodgkin2 were Hodgkins Diseases Disease

1986:1986:2 cases immunostained for 2 cases immunostained for CD15CD15

The Disease:The Disease:

1823 met 1823 met MontefioreMontefiore family family when medical studentwhen medical studentbecame lifelong friend with became lifelong friend with MosesMoses

PhilanthropyPhilanthropy: worked : worked increasingly for poor and increasingly for poor and oppressed (e.g.1838oppressed (e.g.1838--aborigineaborigines protection)s protection)

1863: travelled to Morocco 1863: travelled to Morocco with Moses to intercede with with Moses to intercede with Sultan on behalf of Christians Sultan on behalf of Christians and Jews thereand Jews there

The Mission:The Mission:

The Final Mission:The Final Mission:1865: locusts and cholera decimating Jerusalem1865: locusts and cholera decimating JerusalemJewish board of deputies and Jewish board of deputies and MontefioreMontefiore collect collect 3,000 3,000 for Holy Land Relieffor Holy Land Relief

1866: 1866: MontefioreMontefiore and Hodgkin set out for Jerusalemand Hodgkin set out for Jerusalem

Hodgkin died of Hodgkin died of dysentery or cholera dysentery or cholera 4th April 1866 aged 684th April 1866 aged 68

buried in the English buried in the English cemetery at Jaffacemetery at Jaffa

Caratteristiche morfologicheCaratteristiche morfologiche

Il LH mostra tipici elementi Il LH mostra tipici elementi pluripluri--nucleati, con nucleati, con =60 =60 m e m e nucleoli nucleoli similsimil--inclusionaliinclusionali, , talora acidofili (cellule di Reedtalora acidofili (cellule di Reed--Sternberg o diagnostiche). Sternberg o diagnostiche). Le varianti mononucleate sono Le varianti mononucleate sono chiamate cellule di Hodgkin.chiamate cellule di Hodgkin.Tali cellule assumono carattere Tali cellule assumono carattere diagnosticodiagnostico in un in un pabulumpabuluminfiammatorio. infiammatorio.

Carl Sternberg 1898Carl Sternberg 1898

Dorothy Reed 1902Dorothy Reed 1902

Caratteristiche morfologicheCaratteristiche morfologiche

Il LH mostra tipici elementi Il LH mostra tipici elementi pluripluri--nucleati, con nucleati, con =60 =60 m e m e nucleoli nucleoli similsimil--inclusionaliinclusionali, , talora acidofili (cellule di Reedtalora acidofili (cellule di Reed--Sternberg o diagnostiche). Sternberg o diagnostiche). Le varianti mononucleate sono Le varianti mononucleate sono chiamate cellule di Hodgkin.chiamate cellule di Hodgkin.Tali cellule assumono carattere Tali cellule assumono carattere diagnosticodiagnostico in un in un pabulumpabuluminfiammatorio. infiammatorio.

1 1 3% cellularit3% cellularit

rosetterosetteTT

eosinofilieosinofili endoteliendoteli plasmacelluleplasmacellule midollo osseomidollo osseo

fibroblastifibroblastilinfociti Tlinfociti T

ILIL--99

ILIL--55 ILIL--1, TNF1, TNF

ILIL--1, TNF1, TNF

MM--CSFCSFGG--CSFCSF

ILIL--66

Fenomeni Fenomeni autocriniautocrini e paracrinie paracriniILIL--44 ILIL--88

LGCBD con cellule RSLGCBD con cellule RS--similisimili

Liposarcoma infiammatorioLiposarcoma infiammatorio

Cellule RSCellule RS--similisimili

IstogenesiIstogenesi

Allo stato dellAllo stato dellarte, esiste unanimitarte, esiste unanimit di di pareri circapareri circa

la natura linfoide delle cellule la natura linfoide delle cellule neoplastiche del LH.neoplastiche del LH.

HaraldHarald SteinStein

Nature 1982; 299:65Nature 1982; 299:65--7.7.Blood 1985; 66:848Blood 1985; 66:848--58.58.Am J Pathol 1987; 128:390Am J Pathol 1987; 128:390--3.3.Blood 1989; 74:1678Blood 1989; 74:1678--89.89.Cell 1992; 68:421Cell 1992; 68:421--7.7.Cancer Res 1994; 54:2873Cancer Res 1994; 54:2873--7.7.NEJM 1995; 333:901NEJM 1995; 333:901--66NEJM 1997; 337:453NEJM 1997; 337:453--8.8.J Pathol 2000; 190:613J Pathol 2000; 190:613--8.8.Blood 2000; 95:3020Blood 2000; 95:3020--4.4.Blood 2000; 96:1889Blood 2000; 96:1889--99.99.Blood 2000; 96:3681Blood 2000; 96:3681--95.95.Blood 2001; 97:496Blood 2001; 97:496--501.501.Blood 2002; 99:3060Blood 2002; 99:3060--2.2.Blood 2002; 99:3398Blood 2002; 99:3398--403,403,J Exp Med 2002; 196:605J Exp Med 2002; 196:605--17,17,J Pathol. 2004; 202:60J Pathol. 2004; 202:60--9,9,J Exp Med. 2004;199:1041J Exp Med. 2004;199:1041--52,52,Blood. 2004;104:3326Blood. 2004;104:3326--34. 34.

vacuumvacuum

vacuumvacuum

Single cell PCRSingle cell PCR

ExtrathymicExtrathymic perivascular perivascular spacespace

Thymic folliclesThymic follicles

CD23CD23+ + asteroid Basteroid B--cellscellsMedullary B lymphocytesMedullary B lymphocytes

Fend F et al, Fend F et al, VirchowsVirchows Arch B 60:381, 1991.Arch B 60:381, 1991.TCL1TCL1--, CD27, CD27++: : RemottiRemotti D et al. J Clin D et al. J Clin PatholPathol ((SupplSuppl), 2002.), 2002.CD23CD23++: : CalaminiciCalaminici MR et al, Histopathology 45:619, 2004.MR et al, Histopathology 45:619, 2004.

Thymus: normal B lymphocytesThymus: normal B lymphocytes

CD20CD20CD20CD20

CD20CD20

SeitzSeitz V et al. V et al. BloodBlood 2000; 95:30202000; 95:3020--44

Linfoma di Hodgkin:Linfoma di Hodgkin:attuale inquadramento attuale inquadramento

classificativoclassificativo

LH a prevalenza linfocitaria (4LH a prevalenza linfocitaria (4--5%)5%)

NodulareNodulare DiffusaDiffusa(80%) (80%) (20%)(20%)

Prevalenza linfocitaria nodularePrevalenza linfocitaria nodulare

Caratteri cliniciCaratteri clinici**:: distribuzione unimodale per etdistribuzione unimodale per et((picco a 40 annipicco a 40 anni),),diffusione simile ai LNHdiffusione simile ai LNH, , decorso indolentedecorso indolente,,ricadute tardive (a 10 e piricadute tardive (a 10 e pi anni),anni),occasionale evoluzione in LGCBDoccasionale evoluzione in LGCBD. . ##

** EkstrandEkstrand BC & BC & HorningHorning SJ. Curr Oncol SJ. Curr Oncol RepRep 2002; 4:4242002; 4:424--33.33.## Ohno T et al. Am J Clin Pathol 2001; 116:506Ohno T et al. Am J Clin Pathol 2001; 116:506--11; Huang JZ et al. Leuk 11; Huang JZ et al. Leuk

Lymphoma 2003; 44:1903Lymphoma 2003; 44:1903--20.20.

LH,PL nodulareLH,PL nodulare

Centro germinativo progressiCentro germinativo progressi--vamentevamente trasformato trasformato

Cellule Cellule poppop--corncorn o LPo LP

I centri germinativi progressivamente trasformatiI centri germinativi progressivamente trasformatipossono precedere od associarsi ad un LH,PLpossono precedere od associarsi ad un LH,PLnodulare; pur non essendo precursori morfologicinodulare; pur non essendo precursori morfologiciobbligati, vanno considerati come lesioni a obbligati, vanno considerati come lesioni a rischio.rischio.

Fan Z et al.: Fan Z et al.: Characterization of variant patterns of nodular lymphocyte predoCharacterization of variant patterns of nodular lymphocyte predominant minant Hodgkin lymphoma with Hodgkin lymphoma with immunohistologicimmunohistologic and clinical correlations.and clinical correlations.Am J Surg Pathol 2003; 27:1346Am J Surg Pathol 2003; 27:1346--5656..

Classic nodular pattern, BClassic nodular pattern, B--cellcell--richrich

Serpiginous/interconnected nodular patternSerpiginous/interconnected nodular pattern

Nodular with prominent extraNodular with prominent extra--nodular L&H cellsnodular L&H cells

Nodular with TNodular with T--cellcell--rich backgroundrich background

Diffuse pattern (TCRBCLDiffuse pattern (TCRBCL--like)like)

Diffuse, Diffuse, mothmoth--eateneaten with Bwith B--cellcell--rich backgroundrich background

CD30CD30 --/+ /+ ##CD15CD15 --CD45CD45 ++EMAEMA + + CD20CD20 ++CD79aCD79a --/+/+JJ--chainchain +/+/--BclBcl--66 ++Oct.2, BOBOct.2, BOB--1 & PU.11 & PU.1 ++IRF4IRF4 ++d *d *CD3CD3 --EBVEBV --p53p53 --

pabulum TIApabulum TIA--11++ bassobassopabulum CD57pabulum CD57++/PD1/PD1++ alto alto pabulum CD20pabulum CD20++ altoalto

CFDCFD ++## Roberts C et al. Histopathology 2002; 40:166Roberts C et al. Histopathology 2002; 40:166--70.70.* Carbone A et al. Br J * Carbone A et al. Br J HaematolHaematol 2002; 117:3662002; 117:366--72.72.

ImmunofenotipoImmunofenotipo ((UherovaUherova P et al. Am J Clin P et al. Am J Clin PatholPathol, 2003), 2003)

CD20CD20 CD3/CD57CD3/CD57CD79aCD79a

EMAEMA CD15CD15 CD30CD30

BclBcl--66 Oct2Oct2 CD21CD21

2020--25 September 2008, Bordeaux, France25 September 2008, Bordeaux, France

NLPHL with T/HRLBCLNLPHL with T/HRLBCL--like areaslike areasTypicalTyp