UM EBV+ PROLIFERATIONS - ihot.lt /Limfomos 2011/EBV+... · Intro: Difficulties talking and dealing with EBV Lowlevelofclinical!discrimination ! Lowlevelofdiscriminationofhistological!

EBV+ PROLIFERATIONS UM

LT SPECTRUM IN CONTEXT OF DATA OF 2010/2011

MOTO advices, but please be so kind and JUST WRITE WHAT

Surgeon B

Intro: Difficulties talking and dealing with EBV

Low level of clinical discrimination Low level of discrimination of histological features Not enough experience in pathology IH: EBV LMP1 (2008-‐05-‐26), EBER (2010-‐06-‐15) Transplantation history from 1974: kidney, heart, bone marrow, liver, heart+lung (singles). Pancreas? Intestine? Complex?

Lymphoproliferation vs lymphoma True reactive states/lymphadenopathies: polyclonal, smt monotypic (Ig), smt oligoclonal (EBV) Atypical/borderline lymphoproliferations:

pleomorphic LPDs; LyG I,II°; Castleman d. ): polyclonal/monoclonal; polytypic/monotypic; smt treated as lymphomas; Lymphoma like lesions, monomorphic (gyn tract; germinotropic LPD): polyclonal, monoclonal (?); treatment?

Lymphomas: monoclonal, monotypic (Ig)

Binary paradigm

Lymphoma ( true )

Reactive ( true )

NCP 2010 data

0,4% 0,4% 0,4% 0,4% 0,4% 0,8% 0,8% 0,8% 0,8% 1,2% 1,2% 1,2% 1,6% 1,6%

3,6% 3,6% 3,6% 4,8%

8,0% 9,2% 10,0%

12,8% 32,4%

0,0% 5,0% 10,0% 15,0% 20,0% 25,0% 30,0% 35,0%

Su enteropatija susijusi T limfoma

Burkitto limfoma

Mycosis fungoides

AGE: FOREVER YOUNG AND REACTIVE

Case 1: B11-36165 14 yrs old male;

2.3cm (lateral neck lymphadenopathy).

Case 1: B11-36165 Fol

Hyperplasia Marginal expansion

Case 1: B11-36165 Bcl6 CD30

Ki67 ~85%

Case 1: B11-36165 Ki67

Case 1: B11-36165

Pax-‐5

CD30

CD20 Paracortex

EBER

Case 1: B11-36165 EBV LMP1 Paracortex

Case 1: B11-36165 14 yrs old male; Histo:

FH with lysis; Paracortex expansion with atypical T >> B immunoblasts, CD30+ activated cells, plasmoid cells (immunoblastic lymphadenopathy); Focal marginal zone expansion / immature sinus histiocytosis.

Blood: leucopenia, reactive lymphocytes, high EBV titers, Anti EBV IgM; Active EBV infection (IM): lymphadenopathy.

Case 2: B10-15726 6 yrs old male;

: No clinical data; Tonsilectomy.

Case 2: B10-15726

Necrosis

Ki67

Case 2: B10-15726

CD20

Case 2: B10-15726

EBV LMP1

Ki67 ~85% Paracortex

Case 2: B10-15726 6 yrs old male; No clinical data: tonsilectomy; EBV+ tonsilitis: active EBV infection (IM?); Lost for follow up.

EBV LPL histological signature 1 Geographic necrosis; Imunoblastic expansion: T >> B; Follicular hyperplasia; Extranodal spread; Toxoplasma lymphadenitis ( ) like changes:

histiocytosis Clusters of epithelioid macrophages

Pleomorphic lymphoid infiltrates Angiocentricity HL like cells Plasmablastic/plasmacytoid histology Other

Case off: EBV Dx: B11-30174 32 yrs old female; Neck lymphadenopathy: 2 nodes up to 2,5 cm.

Case off: B11-30174

Marginal expansion

Ma clusters

Case off: B11-30174

Necrosis

Case off: EBV Dx: B11-30174 32 yrs old female; Neck lymphadenopathy: 2 nodes up to 2,5cm; HISTO:

Clustering of Ma; ;

Necrosis; Follicular hyperplasia.

EBER(-‐); toxoplasma (-‐); HHV6+ (PCR) lymphadenopathy (similar clinics to IM); NOTE: EBV, other viral and toxoplasma lymphadenitides share common histological features! Sometimes they imitate B marginal zone lymphomas, more often cHL or DLBCL!

EBV + CONVENTIONAL LYMPHOMAS

Case 3: B10-33601 85 yrs old female; Generalized lymphadenopathy (neck, axillary), B symptoms (2 yrs); BM: reactive changes; LN biopsy (axillary).

Case 3: B10-33601

Clear infiltrate

Case 3: B10-33601

EBV LMP1

CD68

Case 3: B10-33601

EBV LMP1

CD30

CD15

Case 3: B10-33601 85 yrs old female; IH: CD30+100%; CD15+10%; LCA(-‐); EBV LMP1+100%; CD79a(-‐); Pax-‐5+70%; Bcl6(+) 30% (faint);

cellularity (rich with LAM); BM: negative; Treatment: 6 × AVD.

Case off: AILT with EBER+ CD20+CD30+CD15+ giant cells

CD21 FDC network

Case off: AILT: IgH clonal;; IGK polyclonal;; TCR / clonal

EBV EBER

CD30

CD15

CD79a

Case 4: B11-8589 58 yrs old male; 2011 Feb: acute peritonitis, B symptoms, multiple polyps/infiltrates in small intestine, paraaortic lymphadenopathy, slight splenomegaly, multiple infiltrates in the lungs (CT); Biopsy of the pancreatic tumor and resection of perforated small intestine; No history of malabsorbtion.

Case 4: B11-5728

Case 4: B11-5728

CD56

Case 4: B11-5728

CD3

Ki67

Case 4: B11-8589 58 yrs old male; Biopsy from nasopharynx: the same picture; BM negative; DIAGNOSIS: Extranodal NK/T lymphoma, nasal type: EBER+; CD3/CD7/CD56/CD45RO+, Granzym B+, CD2/CD30/CD5/CD4/CD8(-‐); CD43(-‐/+); Ki67 ~ 95%: spread in small intestine with ulceration/perforation and 1/3 node; 6× of intensive chemo: SMILE and R therapy to sinus area Perforation of intestines/peritonitis without signs of tumor; In remission now; NOTE: from 2010 history of nasal polyps treated conservatively!

TRANSPLANT RELATED

Case 5: B11-36567 64 yrs old male; Both kidneys were removed due to nephrolithiasis in 1998; Single kidney transplant in 2000 December; Under Cyclosporin; B11-‐36567: Tumor of the scrotum skin removed: brown 1,5 cm tumor close to margin.

Courtesy of D. Dasevi

Courtesy of D. Dasevi

Case 5: B11-36567

Case 5: B11-36567 Courtesy of D. Dasevi Ki67 CD138

Mum1 LCA

Case 5: B11-36567 IH: LCA+, CD43+, CD138+, MUM1+, CD4+, CD15+, CD8+(5%); Ig kappa/Ig lambda/IgM-‐, Ki67 100%, EBER(-‐); Ig kappa/ Ig lambda/IgM(-‐), EBV LMP1(-‐), TdT/CD34(-‐), CD10/bcl2/CD20/CD79a/PAX5/bcl6(-‐), CD3/CD5/CD2/CD7/ALK1/ D1a/MPO(-‐), CD56/CD30(-‐), PanCK(-‐); DGN: Posttransplant (~11 yrs after kidney Tx) lymphoproliferative disease (PTLD) (monomorphic) EBV(-‐): B plasmablastic lymphoma in the skin; PCR: IgH/IgK clonal; TCR / uninformative; BM: negative; visceral lymphadenopathy; Treatment: R-‐CHOP-‐14; agranulocytosis; febrilic neutropenia; B11-‐36567 (November): kidney transplant was removed (rejection); under hemodialysis now.

https://www.ipath-‐network.com/ltpatho/object/view/26338

https://www.ipath-network.com/ltpatho/object/view/26338



Case 6: B08-24723 36 yrs old male; Renal transplantation in 1993; under immunosupression (mycophenolate mofetil; cyclosporin; steroids); 2008 Feb: chronic rejection (biopsy); Wight loss, B symptoms, rectal pain; CT: neck lymphadenopathy; 2008 Sep: B08-‐24723 biopsy from rectal ulcer; BM: negative.

Case 6: B08-24723

Ki67

CD20: heterogenous

Case 6: B08-24723

Mum1

EBER

Case 6: B08-24723 36 yrs old male; Renal transplantation in 1993; B08-‐24723 biopsy from rectal ulcer; IH: CD20+ (heterogenous), Ki-‐67 ~80%, MUM1+, Bcl2+ (faint), CD10/BCL6(-‐), CD30/CD15 not done; DGN.: DLBCL (PTLD, monomorphic, EBV+ DLBCL) (~15yrs); EBER+ (2011); Trumatic fracture (radius, femur) and delyrium; Treatment (2008): R-‐HiCHOP with endolumbal prophylaxis.

Posttransplant LPD (WHO 2008) Early lesions 99711 (polyclonal):

Plasmacytic hyperplasia; IM like; Other (mass forming FH, other);

Polymorphic 99713 (B clonal, T polyconal) Monomorphic (acording to lymphoma they resemble)(B/T clonal):

DLBCL, Burkitt, Myeloma, Plasmacytoma like, other; PTCL, NOS; Hepatosplenic T cell lymphoma; other.

cHL type PTLD NOTE1: indolent small B cell lymphomas are not included! NOTE2: Most EBV+, some EBV(-‐)! NOTE3: polymoprhic: aggressive, mass forming infiltrate.

Post transplant LPD LT Patie

nt

No

Gend

er

Age

Hospita

l

Dgn

date

DGN

Tx

Tx date

Time

Tx-‐ D

gn

Molecs

BM

T. J. F 60 KMUK 2007 DLBCL (BM) EBV LMP1+

Liver 2006 1year?

Not done (+)

Ar.A B08-‐24723

M 54 Santa

2008 DLBCL (rectum) EBER+

Kidney 1993

15 yrs

Not done (-‐)

Buz.A.

B11-‐16892

M 56 Santa 2011 PTCL (Node/BM) EBER+

BM (CMML)

2010 1 yer Clonal TCR

(+)

Kair.P.

B10-‐33229

M 64 Santa 2010 Plasmablastic LBCL (skin) EBER(-‐)

Kidney 2000 10 yrs IgH/K clonal

(-‐)

Dov.N.

B09-‐3199

F Santa 2009 FL: R-‐CHOP 14 Kidney 2003 ~6 yrs Not done (-‐)

THERAPY RELATED

Case 7: B09-12583 37 yrs old male (2009); 2001: cytopenia and splenomegaly; suspected EBV (IM); Diagnosis of T LGL verified 2007/2009 (BM); Treatment (outside) unknown (Mtx? Oth.?); 2009: small intestine perforation: resection.

Case 7: B09-12583

Case 7: B09-12583

Ig kappa

Ig lambda

Case 7: B09-12583

Ki67

CD138

Case 7: B09-12583

CD8

CD57

CD3

Case 7: B09-12583 Node

EBV LMP1 EBV LMP1

Case 7: B09-12583 37 yrs old male (2009); Probably T LGL from 2001; Small intestine perforation: resection; IH: INFILTRATE: Ki67 ~80% , CD138+ 100%, CD79a+ 20% , Ig kappa/Ig lambda+ (polytypic), Mum1+ 100%. Multiple CD30+ large cells: EBV LMP1/EBER+; Minute T population: CD3/CD2/CD7+ > CD5+, CD56(-‐), CD57+ (in part), CD4+ > CD8+/GranzymB; B09-‐12583: EBV+ LPD (plasmacytic hyperplasia/polymorphic), probably associated with immunosupression/treatment (Mtx?) Minimal T LGL infiltration (TCR clonal; IgH/IgK polyclonal) ???; 2009: DOD after multiple reresections.



Pleomorphic lymphoid infiltrates Angiocentricity HL like cells Plasmablastic/plasmacytoid histology Other: immunosupressive therapy? Tx?

Yatrogenic LPD Similar scheme as in PTLD and age related LPL??? Early lesions: ??? Polymorphic: Mtx Monomorphic (acording to lymphoma they resemble): Mtx (DLBCL; PTCL, NOS) (years) TNF inhibitors (DLBCL, HSTCL, oth.) (weeks-‐months)

cHL: Mtx NOTE: indolent small B cell lymphomas are included!

AGE: NOT SO YOUNG AS BEFORE (>50YRS)

Case 8: B08-16708 67yrs old female; Weakness, B symptoms; visceral and peripheral lymphadenopathy; splenomegaly; pulmonary infiltration; 2004: cervix uteri: poorly differentiated squamous carcinoma (biopsy); B08-‐16708: node biopsy; B08-‐16369: BM biopsy.

Case 8: B08-16708

Ki67

CD30

Case 8: B08-16708 EBER

CD79a

LCA

CD20

Case 8: B08-16708 67yrs old female; 2008 June: B08-‐16708 (node): Age related LBCL (polymorphic) ; IH (ABC): LCA+; CD20+; CD30+; Bcl2+ 100%; p53+ 40%; Mum1+; Bcl6/CD10-‐; Ki67 ~80%; B08-‐16369 (BM): Age related LBCL, 20%; PCR: IgK clonal; IgH polyclonal; Septic shock; Treatment: symptomic; DOD: 2008 June.

http://www.ipath-‐network.com/ltpatho/object/view/5832

http://www.ipath-network.com/ltpatho/object/view/5832



Hess 2010 data

104 106 109

84

5 6 7 9 2 4

8 5 6 3 3 3 3 3 2 1 0

20

40

60

80

100

120

2007 2008 2009 2010

DLBCL, NOS (403)CNS DDBLL (19)

ALK+ LBCL (1)

Case 9: B11-12891 55 yrs old male; Suspition of IM vs PTCL NOS; Lymphadenopathy, splenomegaly, B symptoms, leucocytosis (neutrophylia), low performance; Nodes (2 biopsies) 2011 April-‐May; BM 2011 June/October; Good response to steroids.

Case 9: B11-12891 1st node

Case 9: B11-12891

1st node CD30

Case 9: B11-12891

1st node

CD79a

CD4 > CD8

Ki67

Ig kappa

Case 9: B11-12891

2nd node (after steroids)

Case 9: B11-12891 2nd node (after steroids) EBER

CD3

CD20

Case 9: B11-12891 55 yrs old male; EBV+ IM like lymphadenopathy: CAEBV (age?); Histo LN: T immunoblastic lymphadenopathy and macrophageal reaction ( like, like); BM: pleomorphic focal T CD4+ infiltration and plasmacytosis; IgH and TCR oligoclonal; (DNA degradation) EBER+ (in second biopsy; first RNA/DNA degradation?); Good response to Rituximab.



Pleomorphic lymphoid infiltrates Angiocentricity HL like cells Plasmablastic/plasmacytoid histology Other

Age asociated LPD Similar cheme as in PTLD and yatrogenic LPL??? Early lesions: reactive lymphoid hyperplasia Polymorphic: mucocutaneous ulcer/extranodal, nodal

Monomorphic (according to lymphoma they resemble): Age related DLBCL; Other?

Age related DBCL Patie

nt

Gend

er

Age

Hospita

l

Dgn da

te

Other

DGN

Therap

y

Follo

w

up 2011

Dec

B.I F 67 Santa 2008 July 2004 squamous ca c. uteri; BM+

Age DLBCL

No IgK clon; IgH poly

DOD 2008 July

S.J. M 78 KJL

2011 March

BM(-‐) Age DLBCL

R-‐CHOP 14 ; MINE

Not done Alive, 2011 Oct relapse

P.P M 77 KJL Age DLBCL

R-‐CHOP

Not done

Alive

A.J. M Santa 2011 BM(-‐) Age DLBCL

R-‐CHOP 14 Not done Alive

RARITIES:

64 yrs old male; B10-‐25858 (biopsy): gastric adenocarcinoma; B10-‐27024 (node biopsy): ??? B10-‐28518: gastric resection with lymhonodectomy.

Case 10: B10-28518

Case 10: B10-28518

Part 2: tubular aCA Part 1: medullary

Case 10: B10-28518

CD3 Ig lambda

Case 10: B10-28518

Gastric

Plasmablastic lymhoma

EBER

EBER

64 yrs old male; EBV+ HHV8+ plasmablastic lymphoma (germinotropic LPL) in perigastric 3/29 nodes; Gastric cardiac EBV+ lymphoepithelioma like carcinoma (LELC) : TNM 2010: pT1b (submucosa) N1 (summary: mts 1/29). Intestinal type, Lauren. Radical resection; Clonality (PGR): plasmablastic lymphoma: Ig H clonal; TCR polyclonal; TCR ; TCR clonal; HHV8: positive (PGR); HHV8 (LANA)+ IH (dr.A.Tzankov); HIV (-‐); Follow up: 2011: B11-‐35289 (BM): negative; Treatment: R-‐CHOP 14. http://www.ipath-‐network.com/ltpatho/object/view/25005

Case 10: B10-28518




EBV+ carcinomas

Gastric lymphoepithelioma like carcinoma (LELC), lymphoid stroma rich carcinoma, carcinoma Pancreatic carcinoma; Bile duct carcinoma; Salivary gland carcinoma; Small intestinal carcinoma? Breast carcinoma?

SUMMING UP

EBV+ tumors/proliferations Lymphoid-‐proliferations (LPL); EBV+ FDC sarcoma (IMFT-‐like; spleen/liver); Undifferentiated nasopharyngeal carcinoma EBV+ carcinomas (medullary or lymphoepithelioma like (LELC)): salivary gland, stomach, intestine, pancreas, bile duct, breast, thymus; EBV+ smooth muscle tumor (SMT: benign and malignant, immunodeficiency associated): tonsil, vulva, larynx, bronchi, liver, meninges, urinary bladder; Oral squamous carcinoma.

Nasopharyngeal undifferentiated carcinoma

PanCK

EBER

EBV+ lymphoproliferations EBV+ lymphadenitis, tonsilitis, infectious mononucleosis EBV dermatitis (Gianotti-‐ Crosti s.): papular acrodermatitis of childhood Hairy leucoplakia (mostly HIV) EBV+ gastritis EBV+ polymorphic nodal or extranodal (muco-‐cutaneous ulcer) LPL of elderly/ yatrogenic EBV+ LBCL of elderly

lymphoma (endemic >> sporadic) cHL LyG (I-‐II°) and DLBCL (LyG) EBV+ DLBCL DLBCL asociated with chronic inflammation Primary effusion LBCL Plasmablastic LBCL CLL/SLL with EBV+ giant cells (Fludara associated) CLL/SLL with Richter transformation (EBV+ cHL, clone unrelated) (Fludara associated) germinotropic lymphoproliferation plasmablastic LBCL

EBV+ lymphoproliferations Extranodal T/NK cell lymphoma, nasal type Aggressive NK-‐cell leukaemia Gama/delta hepatosplenic T cell lymphoma (HSTL) (some)?; Gama/delta non-‐hepatosplenic lymphoma; Enteropathy asociated T cell lymphoma (some)? Peripheral T cell lymphoma (some) Angioimmunoblastic T cell lymphoma (AILT) Systemic EBV+ T lymphoproliferative fulminant hemophagocytic Hydroa vacciniforme-‐like lymphoma (Asia, Central, South America nad Mexico) HIV associated (NHL entities: plasmablastic LBCL, cHL, oth.) Primary immunodeficiency associated LPL Treatment associated LPL Transplantation associated PTLD

Immunodeficiency related EBV lymphoproliferations

???

Primary immunodeficiency?

Age related (immunodeficiency?)

Therapy related immunodeficiency

Transplantation related

immunodeficiency

EBV

??? Plasmacytic hyperplasia

Polymorphic LPL (nodal/ extranodal)

Monomorphic nodal/extranodal

(lymphoma)

Mucocutaneous ulcer Traumatic oral granuloma?

Toxoplasma like lymphadenitis

AIDS

Autoimmune disease related

immunodeficiency

Summary 1: when to look for EBV? Every DLBCL after 50yrs: EBV (EBER)? Every LPL with giant cells (HL like), angiocentricity, geographic necrosis: EBV (EBER)?

Plasmablastic LBCL: EBER;

other: EBER; cHL: EBV LMP1? EBER? (prognosis?); Posttransplant LPL setting: EBER; Primary or aquired immunodeficiency asociated LPL: EBER; Undifferentiated carcinomas (head/neck; mts): EBER; Lymphoepithelial/medullary carcinomas: EBER;

like): EBV (EBER)?

Summary 2 Immunodeficiency means not only HIV infection or primary/inherited phenomenon; Reactive EBV related changes are heterogenous vary from classic immunoblastic lymphadenopaty to mucocutaneous ulcer, postransplant like LPL; Borders between LPL and lymphoma sometimes is blurred; EBV is needed for categorization of LPL and for prognostication; The detection of EBV in the tissue/pathology means immunodeficiency in various extent?

Summary 3 The links of HESS with transplantation registry and rheumatic disease registry is needed; Pathology forms must be filled more preciselly (transplantation? Autoimmune disease? Immunocompetence? Viral diseases? HIV? Rheumatic diseases?) EBV LMP1 in NCP: from 2008-‐05-‐26; EBER: from 2010-‐06-‐15; Really we need more experience on LPDs...

New paradigm

Reactive

picture, settings, clonality,

phenotype

Borderline / polymorphic

picture, settings,

clonality, phenotype

Lymphoma

picture, settings, clonality,

phenotype

Literature 1. Dojcinov SD, Venkataraman G, Pittaluga S et al. Age-‐related EBV-‐associated

lymphoproliferative disorders in the Western population: a spectrum of reactive lymphoid hyperplasia and lymphoma. Blood. 2011 May 5;117(18):4726-‐35. Epub 2011 Mar 8.

2. Di Napoli A, Giubettini M, Duranti E et al. Iatrogenic EBV-‐positive lymphoproliferative disorder with features of EBV+ mucocutaneous ulcer: evidence for concomitant TCR IGH rearrangements in the Hodgkin-‐like neoplastic cells. Virchows Arch. 2011 May;458(5):631-‐6. Epub 2011 Mar 12.

3. Dojcinov SD, Venkataraman G, Raffeld M et al. EBV positive mucocutaneous ulcer-‐-‐a study of 26 cases associated with various sources of immunosuppression. Am J Surg Pathol. 2010 Mar;34(3):405-‐17.

4. Age-‐related Epstein-‐Barr virus-‐associated B-‐cell lymphoproliferative disorders: special references to lymphomas surrounding this newly recognized clinicopathologic disease. Shimoyama Y, Yamamoto K, Asano N et al. Cancer Sci. 2008 Jun;99(6):1085-‐91.

5. Swerdlow S H, Campo E. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, Fourth Edition. IARC Press: Lyon, 2008

6. Okano M, Gross TG. Acute or Chronic Life-‐Threatening Diseases Associated With Epstein-‐Barr Virus Infection. Am J Med Sci. 2011 Nov 17. [Epub ahead of print]

7. Hum Pathol. 2007 Sep;38(9):1293-‐304. Epstein-‐Barr virus-‐associated lymphoproliferative disorders. Rezk SA, Weiss LM.

8.

Acknowledgements

Alex and Basel Team The visit to LT and high level hematopatho INCTR iPath community Discusions on the Cases LT Laimonas and Santa Team Every Day Hemato Mindaugas and Klaip da Team Cases from the West LT Vestina, Inga and Kaunas Team Cases from Kaunas Rokas , Graphics and Data analysis Julius Every Day Help/Cases/Photos/Data analysis Gods and Saints Rest of All

Design

EBV+ PROLIFERATIONS UM

LT SPECTRUM IN CONTEXT OF DATA OF 2010/2011

NCP data 2010

344

58

1 0

50

100

150

200

250

300

350

400

NHL cHL NLP HL

NCP data 2010

88 81

58

32 25 23 20

12 9 9 9 6 4 4 3 3 3 2 2 2 2 1 1 1 1 1 1 0

10

20

30

40

50

60

70

80

90

100

Limfomos

NCP data 2010

54

8 7 4 2 2 1 1 1 1

0

10

20

30

40

50

60

DLBC

L NOS

DLBC

L ex M

ZL

DLBC

L Bu

rkit-‐like

DLBC

L ex FL

DLBC

L ex CLL

LYG III°

"Grey zone

" lim

foma su ta

rpiniais DL

BCL ir

LBCL ALK+

DLBC

L Leg type

Difuzin dideli B

NCP data 2010

22

17

6 5

4 4 3

2 2 2 2 2 2 1 1 1 1 1 1 1 1 1

9

0

5

10

15

20

25

Limfm

azgis

Skrand

is

Oda

Retrop

erito

ninis tarpas

Plautis

Kasa

Tarpup

lautis

Pasaita

s

Prieno

sinis antis

Kepe

nys

Galvos s

megen

ys

Kaklas

Bron

chas

Tarpup

lautis

Difuzin dideli B

NCP data 2010

1

11

5

3 3

2

1

0

2

4

6

8

10

12

14

Skrandis Limfmazgis Kepenys

limfoma

-‐ lokalizacijos

HESS preliminary data 2010

144

130

112 113

125

92

29 34

23

14

21 26

31

21

30

13

26 22

15

27

19 23

42

21

14 11

14 15 14 16

10,3

11,8

8,0 7,5

8,9

5,8

0

2

4

6

8

10

12

14

0

20

40

60

80

100

120

140

160

2005 2006 2007 2008 2009 2010

DLBCL SLL MCL MZL FCL DLBCL : FCL

UM EBV+ PROLIFERATIONS - ihot.lt /Limfomos 2011/EBV+... · Intro: Difficulties talking and dealing with EBV Lowlevelofclinical!discrimination ! Lowlevelofdiscriminationofhistological!

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