Een maligne lymfoom is een kwaadaardige woekering van witte bloedcellen die zich meestal manifesteert in lymfeklieren en zich verspreidt via het bloed- en/of lymfestelsel. Lymfomen kunnen in twee categorieën ingedeeld worden; de Hodgkin (HL) en non-Hodgkin lymfomen (NHL). In dit proefschrift worden alleen de NHL besproken. De NHL worden volgens de World Health Organization (WHO) classificatie in verschillende histologische subgroepen ingedeeld. Deze indeling vindt plaats op grond van een combinatie van genetische, histologische, immuunfenotypische en klinische eigenschappen en is belangrijk voor de behandeling. De twee meest voorkomende histologische subgroepen zijn de folliculaire lymfomen (FL) en de diffuus grootcellige lymfomen (DLBCL). FL worden volgens een microscopische methode, de ‘Berard cell counting methode’ in 3 subgroepen gegradeerd; FL graad 1,2 en 3. FL graad 3 kan op basis van de hoeveelheid centroblasten onderverdeeld worden in 3A en 3B. FL3A bestaat uit een gemengde populatie van centroblasten en centrocyten terwijl in FL3B alleen een monotone populatie van centroblasten voorkomt ....

Zie: Nederlandse samenvatting

Bosga-Bouwer, Annigje Geesje,

Een maligne lymfoom is een kwaadaardige woekering van witte bloedcellen die zich meestal manifesteert in lymfeklieren en zich verspreidt via het bloed- en/of lymfestelsel. Lymfomen kunnen in twee categorieën ingedeeld worden; de Hodgkin (HL) en non-Hodgkin lymfomen (NHL). In dit proefschrift worden alleen de NHL besproken. De NHL worden volgens de World Health Organization (WHO) classificatie in verschillende histologische subgroepen ingedeeld. Deze indeling vindt plaats op grond van een combinatie van genetische, histologische, immuunfenotypische en klinische eigenschappen en is belangrijk voor de behandeling. De twee meest voorkomende histologische subgroepen zijn de folliculaire lymfomen (FL) en de diffuus grootcellige lymfomen (DLBCL). FL worden volgens een microscopische methode, de ‘Berard cell counting methode’ in 3 subgroepen gegradeerd; FL graad 1,2 en 3. FL graad 3 kan op basis van de hoeveelheid centroblasten onderverdeeld worden in 3A en 3B. FL3A bestaat uit een gemengde populatie van centroblasten en centrocyten terwijl in FL3B alleen een monotone populatie van centroblasten voorkomt .... Zie: Nederlandse samenvattin

Bosga-Bouwer, Annigje Geesje

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Follicular Lymphoma grade 3B. A separate entity?

University of Groningen

   University of GroningenFollicular Lymphoma grade 3B. A separate entity?Bosga-Bouwer, Annigje GeesjeIMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite fromit. Please check the document version below.Document VersionPublisher's PDF, also known as Version of recordPublication date:2006Link to publication in University of Groningen/UMCG research databaseCitation for published version (APA):Bosga-Bouwer, A. G. (2006). Follicular Lymphoma grade 3B. A separate entity?. Groningen: s.n.CopyrightOther than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of theauthor(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons).Take-down policyIf you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediatelyand investigate your claim.Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons thenumber of authors shown on this cover page is limited to 10 maximum.Download date: 12-11-2019 Appendix  105Appendix     Supplementary clinical data, treatment results and additional immunohistochemistry data of FL3B cases.   Supplementary data of FL3B cases  106 The patients included in this study are all adults and were diagnosed as FL3B at time of the obtained biopsy. Patients were classified using clinical data and treatment data for both primary and secondary FL3B. The clinical data from 28 patients with the primary and secundary diagnosis FL3B are summarised in Table A1. From 2 patients was no clinical data available and in 2 cases it concerns a sequential biopsy.   The treatment data includes details of treatment in 18 patients with the  primary diagnosis FL3B (Table A2a). Ten patients were diagnosed with NHL and treated before the biopsy was obtained on which the diagnosis FL3B was based and of which the cytogenetic results were obtained (Table A2b).   In addition, we investigated our panel of 30 cases with special emphasis on BCL6, CD10 and MUM1/IRF4 expression and the 3 different subgroups with  I: a 3q27 abberation and no t(14;18), II: a subgroup with none of these abberations and III: a t(14;18) without a 3q27 abberation. (Table A3)             Appendix  107Table A1: Clinical Data.from 28 patients with the diagnosis FL3B.   N=28 % Age Median: 57.6   Range: 29-85  Sex Male: 17 61%  Female: 11 39% B-symptoms Yes: 4 13% Clinical stage I-IA: 5 18%  II: 8 28%  III-IV: 15 54% WHO performance score 1-2: 7 25%  3-4: 0 0% BM involvement Yes: 7 25% E-localisation 1 Yes: 9 32% Bulky mass 2 Yes: 7 25% LDH >> 3 Yes: 10 36% IP-index 0-1: 16 57%  2-3: 12 43%  4-5: 0 0% Survival First diagnosis -> last follow up: Median Range 5.6 years 7months-25 years  1 other than BM 2 > 10 cm 3 normal = < 400 Supplementary data of FL3B cases  Table A2a: Cytogenetic grouping and treatment results of 18 patients with the primary diagnosis FL3B. Subgroup Case primary diagnosis Primary therapy Response No of relapses Subtype OS Ia 2 FL3B 6xCHOP + XRT PR ?  ? GC ?? I 25 FL3B 12xCHOP-like CR 1  DOC GC 14 months I 29 FL3B XRT 3500Gy CR 0  A GC? > 4.5 years II 9 FL3B Excision lymphnode CR 1  A (NED) GC > 3years II 12 Rec.na prim.FL3B 6xCHOP, 5xCEP CR 2  A (NED) GC > 9 years II 8 FL3B 6xCHOP CR 0  A (NED) ABC > 9 years II 15 FL3B 4xCHOP PD 1  DOD ABC 1.5 years II 16 FL3B 1xCHOP,4xCOP,1xCHOP, 1xCHOP PR 1  AWD GC > 8 years II 18 FL3B 7xCHOP,1xmini-BEAM PD 0  DOD GC 7 months II 19 FL3B 4xCHOP,1xDHAP,1xmini-BEAM NR/PD 0  DOD GC 9 months II 32 FL3B XRT 40Gy (2 months) CR 0  A (NED) ?? > 4 years III 10 FL3B 5xCP PR 1  DOC GC 2 years III 11 FL3B 3xCHOP,1xXRT 30Gy CR 0  A (NED) GC > 7 years III 13 FL3B 6xCHOP CR 3  A (NED) GC > 6 years III 20 FL3B 8xCHOP CR 0  A (NED) GC > 7 years III 21 FL3B 6xCHOP/MTX,after 17 months x8 CR 3  DOD ?? 4.5 years III 26 FL3B 12xVACOP-B ,XRT2500Gy,+other PR/CR 1  DOD GC 4 years III 27 FL3B 12xVACOP-B + XRT250Gy CR 0  A (NED) GC > 8 years I: t(14;18) negative and 3q27 positive, II: t(14;18) and 3q27 negative, III: t(14;18) positive and 3q27 negative, a : incomplete data; A: Alive, D: Dead, AWD: alive with disease, DOD: dead of disease, DOC: dead of other cause, NED: no evidence of disease. GC: Germinal Center like lymphoma, ABC: Activated B-Cell lymphoma, CR: complete response, PR: partial response, PD: partial disease, NR: no response, OS: overall survival  Appendix  Table A2b: Cytogenetic grouping of 10 patients with an antecedent NHL diagnosis, treatment results and time to diagnosis FL3B. subgroup Case Antecedent diagnosis Primary Therapy Response Time to FL3B Therapy after transformation Response No of relapses Subtype OS 10; 6;5;2 years 6xLPP PR 5  DOD GC 25 years I 17 FL1,2 MVPP,chl.amb,CHOP,DHAP,XRT CR/PR 17 months      I 4 DLBCL XRT + 6xCOP CR 9 years 3xCHOP/MTX + 5xCHOP/MTX PR 2  DOD ABC 12 years I 6 FL3B? Leukeran/plasmapheresis PR 4 years 3xCHOP PR 2  DOD ABC 5 years I 30 FL1,2 Prednisolone (10wks) PR 5 years No therapy CR 1  A (NED) GC > 14 years II 1 IBL./DLBCL 7xCHOP CR 10 months 6xMOPP/APOV CR 2  AWD ABC 2 years II 5 DLBCL XRT+6xCOP,6xCHOP CR 12,5 years 4xpromaceMOPP,ABMT, leukeran PR 2  DOD ABC 13 years III 7 FL1,2 8x fludarabine PR 20 months 1xCHOP,MACOP-B PR/PD 2  DOD ?? 2 years III 14 FL1,2 9xLeukeran,10xCOP,7xMOPP, 2xCHOP PD/NR 8 years DHAP/VIM/DHAP ?? 2  DOD GC 9 years 14x(Cyclo+BCNU+Vinc.+predn. 6xCHOP-like + XRT3500Gy CR 2  DOC ?? 22 years III 28 FL1,2  CR 17 years      III 31 FL1,2 No therapy ?? 2 years 6xCNOP PR 2  DOD GC 5,5 years  I: t(14;18) negative and 3q27 positive, II: t(14;18) and 3q27 negative, III: t(14;18) positive and 3q27 negative A: Alive, D: Dead, AWD: alive with disease, DOD: dead of disease, DOC: dead of other cause, NED: no evidence of disease. GC: Germinal Center like B-cell lymphoma, ABC: Activated B-Cell lymphoma, CR: complete response, PR: partial response, PD: partial disease, NR: no response, OS: overall survivalSupplementary data of FL3B cases 110 Table A3: Expression data of FL3B cases for BCL6, CD10 and MUM1 Case nr Bcl6 CD10 MUM1 combination paraffin and frozen tissue subtype Primary diagnosis   I:  3q27 break  no t(14;18)         2 + + - GC FL3B 6 + - + ABC FL3B ->FL3B? 17 + - - GC FL1,2 ->FL3B 22** + ND ND     FL3B  25 +/- + - GC FL3B 29 + - - ? GC? FL3B 30 + - - CG FL1,2 ->FL3B 4 + - + ABC DLBCL ->FL3B           II:  no 3q27 break  no t(14;18)         1 + - + ABC IBL ->FL3B 5 + - + ABC DLBCL ->FL3B 8 + - + ABC FL3B 15** + - + ABC FL3B 16 + - - GC FL3B 18 + + - GC FL3B 19 + + -  GC FL3B 24 ++ -  - ? GC? no data  32 + -     FL3B  9 + - - GC FL3B 12 + + + GC FL3B           III:  t(14;18)   no 3q27 break        7 + ND ND   FL1,2 FL3B 10 +  + - GC FL3B 11 +  - ND GC FL3B 13 +  + - GC FL3B 14 +  + - GC FL1,2 FL3B 20 +  - - GC FL3B 21 ND ND ND   FL3B 26 ND  + ND GC FL3B 27 ND  + - GC FL3B 28 ND  - -   FL1,2 FL3B 31 +  + ND GC FL1,2 FL3B  GC: Germinal Center like B-cell lymphoma, ABC: Activated B-Cell lymphoma ND: not done, ^ 3q27 pos. with Southern Blot hybridization; ** cases with a sequential biopsy. 

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 University of Groningen
Follicular Lymphoma grade 3B. A separate entity?
Bosga-Bouwer, Annigje Geesje
IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite from
it. Please check the document version below.
Document Version
Publisher's PDF, also known as Version of record
Publication date:
2006
Link to publication in University of Groningen/UMCG research database
Citation for published version (APA):
Bosga-Bouwer, A. G. (2006). Follicular Lymphoma grade 3B. A separate entity? Groningen: s.n.
Copyright
Other than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of the
author(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons).
Take-down policy
If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately
and investigate your claim.
Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons the
number of authors shown on this cover page is limited to 10 maximum.
Download date: 10-02-2018
  
Follicular Lymphoma grade 3B 
A separate entity? 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
©Copyright, Anneke Bosga, 2006  
 
All rights reserved. No parts of this publication may be reproduced or transmitted in any form or 
by any means, without permission of the author. 
 
Cover: Anneke Bosga, Leon Bosga (13), Freddie Snackers (15) 
 
Printed by: PrintPartners Ipskamp B.V., Enschede, The Netherlands 
RIJKSUNIVERSITEIT GRONINGEN 
 
 
Follicular Lymphoma grade 3B 
A separate entity? 
 
 
Proefschrift 
 
 
ter verkrijging van het doctoraat in de 
Medische Wetenschappen 
aan de Rijksuniversiteit Groningen 
op gezag van de 
Rector Magnificus, dr. F. Zwarts, 
in het openbaar te verdedigen op 
woensdag 20 december 2006 
om 13.15 uur 
 
 
 
door 
 
 
 
Annigje Geesje Bosga-Bouwer 
 
 
 
geboren op 16 oktober 1959 
te Zuidwolde (Dr.) 
Promotores: Prof. dr. S. Poppema 
 Prof. dr. P. Kluin 
 
Copromotores: Dr. A.van den Berg 
 Dr. E.van den Berg-de Ruiter 
 
 
 
Beoordelingscommissie: Prof. dr. B.de Jong 
 Prof. dr. H. Hollema 
 Prof. dr. H. Schouten 
 
 
Paranimfen: A. Braam 
 N.Folkers 
CONTENTS 
 
 
Chapter 1 9 
General Introduction   
 
Chapter 2 31 
Follicular lymphoma grade 3B includes 3 cytogenetically defined subgroups with 
primary t(14;18), 3q27, or other translocations: t(14;18) and 3q27 are mutually 
exclusive.  
(Blood. 2003;101:1149-1154) 
 
Chapter 3 49 
BCL6 Alternative Translocation Breakpoint Cluster Region associated with 
Follicular Lymphoma Grade 3B.  
(Genes Chromosomes & Cancer. 2005;44:301-304) 
 
Chapter 4 61 
Molecular, cytogenetic, and immunophenotypic characterization of follicular 
lymphoma grade 3B; a separate entity or part of the spectrum of diffuse large  
B-cell lymphoma or follicular lymphoma?  
(Human Pathology. 2006;37:528-533) 
 
Chapter 5 75 
Array CGH reveals a very high frequency of deletions of the long arm of 
chromosome 6 in Testicular Lymphoma.  
(Genes Chromosomes & Cancer, 2006;45:976-81) 
 
Chapter 6 91 
Summary & Discussion 
 
Appendix 105 
Supplementary clinical data, treatment results and additional 
immunohistochemistry data of FL3B cases. 
 
Nederlandse samenvatting 111 
 
Dankwoord 119 
 
List of publications 123 
 


Follicular Lymphoma grade 3B. A separate entity?

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