K Koch1, E Hoster2, M Ziepert3, M Unterhalt4, G Ott5, A Rosenwald6, M L Hansmann7, W Bernd8, H Stein9, V Pöschel10, M Dreyling4, L Trümper11, M Löffler3, N Schmitz12, W Hiddemann4, M Pfreundschuh10, W Klapper13. 1. Department of Pathology, Hematopathology Section and Lymph Node Registry, University Hospital Schleswig-Holstein, Campus Kiel. 2. Department of Internal Medicine III, University Hospital of Munich, Munich Institute for Medical Informatics, Biometry, and Epidemiology, University Munich, Munich. 3. Institute for Medical Informatics, Statistics, and Epidemiology, University Leipzig, Leipzig. 4. Department of Internal Medicine III, University Hospital of Munich, Munich. 5. Department of Clinical Pathology, Robert Bosch Krankenhaus, and Dr Margarete Fischer-Bosch Institut für Klinische Pharmakologie, Stuttgart. 6. Institute of Pathology, University of Würzburg, Würzburg Comprehensive Cancer Center Mainfranken, Würzburg. 7. Institute of Pathology, University of Frankfurt, Frankfurt. 8. Department of Pathology, University of Lübeck, Lübeck. 9. Pathodiagnostik, Berlin. 10. Medizinische Klinik I, Saarland University Medical School, Homburg/Saar. 11. Department of Hematology and Oncology, Georg-August University, Göttingen. 12. Department of Hematology, Asklepios Klinik St Georg, Hamburg, Germany. 13. Department of Pathology, Hematopathology Section and Lymph Node Registry, University Hospital Schleswig-Holstein, Campus Kiel wklapper@path.uni-kiel.de.
Abstract
BACKGROUND: Histologically, follicular lymphoma (FL) grades 1, 2 and 3A are composed of two distinct cell types, centroblasts and centrocytes. FL grade 3B is composed only of centroblasts and has been shown to differ in immunophenotype and genetics from FL that contain centrocytes. We aimed to understand the pathogenetic and clinical relation between FL grade 3A to FL grade 1/2 on the one hand and FL grade 3B on the other hand. PATIENTS AND METHODS: Trial patients with long-term follow-up and diagnosis of FL grade 3 were selected and samples underwent a second central pathological review using a multiple-observer approach to assess grading. RESULTS: Interobserver variability for diagnosing FL grade 3 was high. FL grade 3A frequently harbored areas of FL grade 1/2 within the same tissue specimen. FL grade 3B rarely coexisted with grade 1/2 or 3A, suggesting divergent pathogenesis. There was no statistically significant difference in outcome between 47 cases of FL grade 3A and 14 cases of grade 3B. Compared with grade 1/2 FL, both groups showed longer progression-free survival without late events, especially after immunochemotherapy; this outcome difference was retained after adjustment for clinical prognostic factors. The subgroup of FL grade 3A with an additional FL grade 1/2 component or a translocation t(14;18) showed a poorer outcome. In contrast, the FL grade 3A lacking t(14;18) and of localized stage resembled the pediatric type of FL and showed a very good outcome. FL3 with MYC breaks showed a poor outcome. CONCLUSIONS: The results suggest that first-line immunochemotherapy might allow long-lasting remissions in a subgroup of FL grade 3A similar to diffuse large B-cell lymphoma. Within FL3A, prognostic subgroups can be identified by analyzing for coexisting FL1/2 and MYC breaks.
BACKGROUND: Histologically, follicular lymphoma (FL) grades 1, 2 and 3A are composed of two distinct cell types, centroblasts and centrocytes. FL grade 3B is composed only of centroblasts and has been shown to differ in immunophenotype and genetics from FL that contain centrocytes. We aimed to understand the pathogenetic and clinical relation between FL grade 3A to FL grade 1/2 on the one hand and FL grade 3B on the other hand. PATIENTS AND METHODS: Trial patients with long-term follow-up and diagnosis of FL grade 3 were selected and samples underwent a second central pathological review using a multiple-observer approach to assess grading. RESULTS: Interobserver variability for diagnosing FL grade 3 was high. FL grade 3A frequently harbored areas of FL grade 1/2 within the same tissue specimen. FL grade 3B rarely coexisted with grade 1/2 or 3A, suggesting divergent pathogenesis. There was no statistically significant difference in outcome between 47 cases of FL grade 3A and 14 cases of grade 3B. Compared with grade 1/2 FL, both groups showed longer progression-free survival without late events, especially after immunochemotherapy; this outcome difference was retained after adjustment for clinical prognostic factors. The subgroup of FL grade 3A with an additional FL grade 1/2 component or a translocation t(14;18) showed a poorer outcome. In contrast, the FL grade 3A lacking t(14;18) and of localized stage resembled the pediatric type of FL and showed a very good outcome. FL3 with MYC breaks showed a poor outcome. CONCLUSIONS: The results suggest that first-line immunochemotherapy might allow long-lasting remissions in a subgroup of FL grade 3A similar to diffuse large B-cell lymphoma. Within FL3A, prognostic subgroups can be identified by analyzing for coexisting FL1/2 and MYC breaks.
Authors: Lisa M Rimsza; Hongli Li; Rita M Braziel; Catherine M Spier; Daniel O Persky; Jennifer Dunlap; Michael LeBlanc; Nancy Bartlett; John P Leonard; Sonali M Smith; Oliver W Press; Jonathan W Friedberg Journal: Haematologica Date: 2018-02-22 Impact factor: 9.941
Authors: Rita Alaggio; Catalina Amador; Ioannis Anagnostopoulos; Ayoma D Attygalle; Iguaracyra Barreto de Oliveira Araujo; Emilio Berti; Govind Bhagat; Anita Maria Borges; Daniel Boyer; Mariarita Calaminici; Amy Chadburn; John K C Chan; Wah Cheuk; Wee-Joo Chng; John K Choi; Shih-Sung Chuang; Sarah E Coupland; Magdalena Czader; Sandeep S Dave; Daphne de Jong; Ming-Qing Du; Kojo S Elenitoba-Johnson; Judith Ferry; Julia Geyer; Dita Gratzinger; Joan Guitart; Sumeet Gujral; Marian Harris; Christine J Harrison; Sylvia Hartmann; Andreas Hochhaus; Patty M Jansen; Kennosuke Karube; Werner Kempf; Joseph Khoury; Hiroshi Kimura; Wolfram Klapper; Alexandra E Kovach; Shaji Kumar; Alexander J Lazar; Stefano Lazzi; Lorenzo Leoncini; Nelson Leung; Vasiliki Leventaki; Xiao-Qiu Li; Megan S Lim; Wei-Ping Liu; Abner Louissaint; Andrea Marcogliese; L Jeffrey Medeiros; Michael Michal; Roberto N Miranda; Christina Mitteldorf; Santiago Montes-Moreno; William Morice; Valentina Nardi; Kikkeri N Naresh; Yasodha Natkunam; Siok-Bian Ng; Ilske Oschlies; German Ott; Marie Parrens; Melissa Pulitzer; S Vincent Rajkumar; Andrew C Rawstron; Karen Rech; Andreas Rosenwald; Jonathan Said; Clémentine Sarkozy; Shahin Sayed; Caner Saygin; Anna Schuh; William Sewell; Reiner Siebert; Aliyah R Sohani; Reuben Tooze; Alexandra Traverse-Glehen; Francisco Vega; Beatrice Vergier; Ashutosh D Wechalekar; Brent Wood; Luc Xerri; Wenbin Xiao Journal: Leukemia Date: 2022-06-22 Impact factor: 12.883
Authors: Heike Horn; Christian Kohler; Raphael Witzig; Markus Kreuz; Ellen Leich; Wolfram Klapper; Michael Hummel; Markus Loeffler; Lorenz Trümper; Rainer Spang; Andreas Rosenwald; German Ott Journal: Haematologica Date: 2018-03-22 Impact factor: 9.941
Authors: Z T Ying; H Y Feng; L Mi; Y Q Song; X P Wang; W Zheng; N J Lin; M F Tu; Y Xie; L Y Ping; C Zhang; W P Liu; L J Deng; J Zhu Journal: Zhonghua Xue Ye Xue Za Zhi Date: 2018-09-14