BACKGROUND: According to the current World Health Organization Classification of Lymphoid Tumours, follicular lymphoma is subclassified into three grades according to the number of centroblasts. Follicular lymphoma grade 3 can be further divided into types A and B. Almost all available genetic data on grade 3B follicular lymphomas have been generated from tumors with an additional diffuse large B-cell lymphoma component. The purely follicular type of follicular lymphoma grade 3B is a rare neoplasm. DESIGN AND METHODS: We performed a detailed immunohistochemical (CD10, IRF4/MUM1, BCL2, Ig light chains) and genetic (translocations of BCL2, BCL6, MYC, IRF4) characterization of the largest series of purely follicular cases of grade 3B follicular lymphoma available to date, comprising 23 tumor samples. We also included 25 typical grade 1 or 2 follicular lymphomas, 9 follicular lymphomas with large centrocytes and/or high proliferation indices (FL/LCC), 12 cases of follicular lymphoma grade 3A, 16 cases of diffuse large B-cell lymphoma/follicular lymphoma grade 3B and 15 follicular lymphomas in which a straightforward distinction between grades 3A and 3B was not possible. RESULTS: Translocations affecting BCL2 and BCL6 genes are rare in grade 3B follicular lymphomas (2/23, 9% and 4/23, 17%) when compared with grade 1 or 2 follicular lymphomas (22/25, 88%, P<0.001 and 0/25, P<0.05), FL/LCC (7/9, 78%, P<0.001 and 2/9, 22%), grade 3A follicular lymphomas (7/12, 58%, P<0.01 and 2/12, 17%), unclassified grade 3 follicular lymphomas (6/15, 40% and 2/15, 13%) and diffuse large B-cell lymphoma/follicular lymphoma grade 3B (2/16, 13% and 8/16, 50%, P<0.05). MYC translocations were detected occasionally in FL/LCC, follicular lymphoma grade 3B, and diffuse large B-cell lymphoma/follicular lymphoma grade 3B (13%-22%), but not in grade 1, 2 or 3A follicular lymphomas (P<0.05 when compared with follicular lymphoma grade 3B). Both follicular lymphoma grade 3B and diffuse large B-cell lymphoma/follicular lymphoma grade 3B were enriched in samples with a CD10(-)IRF4/MUM1(+) immunophenotype (8/19, 42% and 7/16, 44%), with the vast majority of them lacking BCL2 translocations. In contrast, 42/46 grade 1 or 2 follicular lymphomas, FL/LCC and grade 3A follicular lymphomas were CD10(+) (91%) while 0/46 expressed IRF4/MUM1. None of the tumor samples tested with increased IRF4/MUM1-expression harbored a translocation of the IRF4 gene locus. CONCLUSIONS: Our results show that grade 3B follicular lymphomas form a distinct category of follicular lymphomas with infrequent BCL2 and BCL6 translocations, while grades 1, 2 and 3A follicular lymphomas and FL/LCC display homogeneous features with frequent BCL2 translocations and a CD10(+)IRF4/MUM1(-) immunophenotype.
BACKGROUND: According to the current World Health Organization Classification of Lymphoid Tumours, follicular lymphoma is subclassified into three grades according to the number of centroblasts. Follicular lymphoma grade 3 can be further divided into types A and B. Almost all available genetic data on grade 3B follicular lymphomas have been generated from tumors with an additional diffuse large B-cell lymphoma component. The purely follicular type of follicular lymphoma grade 3B is a rare neoplasm. DESIGN AND METHODS: We performed a detailed immunohistochemical (CD10, IRF4/MUM1, BCL2, Ig light chains) and genetic (translocations of BCL2, BCL6, MYC, IRF4) characterization of the largest series of purely follicular cases of grade 3B follicular lymphoma available to date, comprising 23 tumor samples. We also included 25 typical grade 1 or 2 follicular lymphomas, 9 follicular lymphomas with large centrocytes and/or high proliferation indices (FL/LCC), 12 cases of follicular lymphoma grade 3A, 16 cases of diffuse large B-cell lymphoma/follicular lymphoma grade 3B and 15 follicular lymphomas in which a straightforward distinction between grades 3A and 3B was not possible. RESULTS: Translocations affecting BCL2 and BCL6 genes are rare in grade 3B follicular lymphomas (2/23, 9% and 4/23, 17%) when compared with grade 1 or 2 follicular lymphomas (22/25, 88%, P<0.001 and 0/25, P<0.05), FL/LCC (7/9, 78%, P<0.001 and 2/9, 22%), grade 3A follicular lymphomas (7/12, 58%, P<0.01 and 2/12, 17%), unclassified grade 3 follicular lymphomas (6/15, 40% and 2/15, 13%) and diffuse large B-cell lymphoma/follicular lymphoma grade 3B (2/16, 13% and 8/16, 50%, P<0.05). MYC translocations were detected occasionally in FL/LCC, follicular lymphoma grade 3B, and diffuse large B-cell lymphoma/follicular lymphoma grade 3B (13%-22%), but not in grade 1, 2 or 3A follicular lymphomas (P<0.05 when compared with follicular lymphoma grade 3B). Both follicular lymphoma grade 3B and diffuse large B-cell lymphoma/follicular lymphoma grade 3B were enriched in samples with a CD10(-)IRF4/MUM1(+) immunophenotype (8/19, 42% and 7/16, 44%), with the vast majority of them lacking BCL2 translocations. In contrast, 42/46 grade 1 or 2 follicular lymphomas, FL/LCC and grade 3A follicular lymphomas were CD10(+) (91%) while 0/46 expressed IRF4/MUM1. None of the tumor samples tested with increased IRF4/MUM1-expression harbored a translocation of the IRF4 gene locus. CONCLUSIONS: Our results show that grade 3B follicular lymphomas form a distinct category of follicular lymphomas with infrequent BCL2 and BCL6 translocations, while grades 1, 2 and 3A follicular lymphomas and FL/LCC display homogeneous features with frequent BCL2 translocations and a CD10(+)IRF4/MUM1(-) immunophenotype.
Authors: Christine P Hans; Dennis D Weisenburger; Julie M Vose; Lynette M Hock; James C Lynch; Patricia Aoun; Timothy C Greiner; Wing C Chan; Robert G Bociek; Philip J Bierman; James O Armitage Journal: Blood Date: 2002-11-07 Impact factor: 22.113
Authors: Matija Snuderl; Olga K Kolman; Yi-Bin Chen; Jessie J Hsu; Adam M Ackerman; Paola Dal Cin; Judith A Ferry; Nancy Lee Harris; Robert P Hasserjian; Lawrence R Zukerberg; Jeremy S Abramson; Ephraim P Hochberg; Hang Lee; Alfred I Lee; Christiana E Toomey; Aliyah R Sohani Journal: Am J Surg Pathol Date: 2010-03 Impact factor: 6.394
Authors: Anneke G Bosga-Bouwer; Anke van den Berg; Eugenia Haralambieva; Debora de Jong; Ronald Boonstra; Philip Kluin; Eva van den Berg; Sibrand Poppema Journal: Hum Pathol Date: 2006-05 Impact factor: 3.466
Authors: Eric D Hsi; Imran Mirza; Gerard Lozanski; John Hill; Brad Pohlman; Matthew T Karafa; Robert Coupland Journal: Arch Pathol Lab Med Date: 2004-08 Impact factor: 5.534
Authors: Ellen Leich; Itziar Salaverria; Silvia Bea; Andreas Zettl; George Wright; Victor Moreno; Randy D Gascoyne; Wing-Chung Chan; Rita M Braziel; Lisa M Rimsza; Dennis D Weisenburger; Jan Delabie; Elaine S Jaffe; Andrew Lister; Jude Fitzgibbon; Louis M Staudt; Elena M Hartmann; Hans-Konrad Mueller-Hermelink; Elias Campo; German Ott; Andreas Rosenwald Journal: Blood Date: 2009-05-26 Impact factor: 22.113
Authors: Anneke G Bosga-Bouwer; Gustaaf W van Imhoff; Ronald Boonstra; Anneke van der Veen; Eugenia Haralambieva; Anke van den Berg; Bauke de Jong; Vanessa Krause; Martin C Palmer; Robert Coupland; Philip M Kluin; Eva van den Berg; Sibrand Poppema Journal: Blood Date: 2003-02-01 Impact factor: 22.113
Authors: I Chau; R Jones; D Cunningham; A Wotherspoon; N Maisey; A R Norman; P Jain; L Bishop; A Horwich; D Catovsky Journal: Br J Cancer Date: 2003-07-07 Impact factor: 7.640
Authors: Sietse M Aukema; Markus Kreuz; Christian W Kohler; Maciej Rosolowski; Dirk Hasenclever; Michael Hummel; Ralf Küppers; Dido Lenze; German Ott; Christiane Pott; Julia Richter; Andreas Rosenwald; Monika Szczepanowski; Carsten Schwaenen; Harald Stein; Heiko Trautmann; Swen Wessendorf; Lorenz Trümper; Markus Loeffler; Rainer Spang; Philip M Kluin; Wolfram Klapper; Reiner Siebert Journal: Haematologica Date: 2013-10-31 Impact factor: 9.941
Authors: Luc Xerri; Stephan Dirnhofer; Leticia Quintanilla-Martinez; Birgitta Sander; John K C Chan; Elias Campo; Steven H Swerdlow; German Ott Journal: Virchows Arch Date: 2015-10-19 Impact factor: 4.064
Authors: E Leich; E Hoster; M Wartenberg; M Unterhalt; R Siebert; K Koch; W Klapper; M Engelhard; B Puppe; H Horn; A M Staiger; C Stuhlmann-Laeisz; H W Bernd; A C Feller; M Hummel; D Lenze; H Stein; S Hartmann; M L Hansmann; P Möller; W Hiddemann; M Dreyling; G Ott; A Rosenwald Journal: Leukemia Date: 2015-12-01 Impact factor: 11.528
Authors: Dominik Nann; Joan Enric Ramis-Zaldivar; Inga Müller; Blanca Gonzalez-Farre; Janine Schmidt; Caoimhe Egan; Julia Salmeron-Villalobos; Guillem Clot; Sven Mattern; Franziska Otto; Barbara Mankel; Dolors Colomer; Olga Balagué; Vanessa Szablewski; Carmen Lome-Maldonado; Lorenzo Leoncini; Stefan Dojcinov; Andreas Chott; Christiane Copie-Bergman; Irina Bonzheim; Falko Fend; Elaine S Jaffe; Elias Campo; Itziar Salaverria; Leticia Quintanilla-Martinez Journal: Blood Adv Date: 2020-11-24