Clinical, pathological and genetic features of follicular lymphoma grade 3A: a joint analysis of the German low-grade and high-grade lymphoma study groups GLSG and DSHNHL.
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.



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.



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.



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.
Department of Pathology, Hematopathology Section and Lymph Node Registry, University Hospital Schleswig-Holstein, Campus Kiel.
K
K
Koch
Department of Internal Medicine III, University Hospital of Munich, Munich Institute for Medical Informatics, Biometry, and Epidemiology, University Munich, Munich.
E
E
Hoster
Institute for Medical Informatics, Statistics, and Epidemiology, University Leipzig, Leipzig.
M
M
Ziepert
Department of Internal Medicine III, University Hospital of Munich, Munich.
M
M
Unterhalt
Department of Clinical Pathology, Robert Bosch Krankenhaus, and Dr Margarete Fischer-Bosch Institut für Klinische Pharmakologie, Stuttgart.
G
G
Ott
Institute of Pathology, University of Würzburg, Würzburg Comprehensive Cancer Center Mainfranken, Würzburg.
A
A
Rosenwald
Institute of Pathology, University of Frankfurt, Frankfurt.
M L
ML
Hansmann
Department of Pathology, University of Lübeck, Lübeck.
W
W
Bernd
Pathodiagnostik, Berlin.
H
H
Stein
Medizinische Klinik I, Saarland University Medical School, Homburg/Saar.
V
V
Pöschel
Department of Internal Medicine III, University Hospital of Munich, Munich.
M
M
Dreyling
Department of Hematology and Oncology, Georg-August University, Göttingen.
L
L
Trümper
Institute for Medical Informatics, Statistics, and Epidemiology, University Leipzig, Leipzig.
M
M
Löffler
Department of Hematology, Asklepios Klinik St Georg, Hamburg, Germany.
N
N
Schmitz
Department of Internal Medicine III, University Hospital of Munich, Munich.
W
W
Hiddemann
Medizinische Klinik I, Saarland University Medical School, Homburg/Saar.
M
M
Pfreundschuh
Department of Pathology, Hematopathology Section and Lymph Node Registry, University Hospital Schleswig-Holstein, Campus Kiel wklapper@path.uni-kiel.de.
W
W
Klapper
D002887:Chromosomes, Human, Pair 18 / Q000235:genetics; D018572:Disease-Free Survival; D005260:Female; D005858:Germany; D006801:Humans; D016130:Immunophenotyping / Q000379:methods; D008224:Lymphoma, Follicular / Q000145:classification / Q000235:genetics* / Q000473:pathology*; D008228:Lymphoma, Non-Hodgkin / Q000145:classification / Q000235:genetics* / Q000473:pathology*; D008297:Male; D060787:Neoplasm Grading; D010338:Pathology, Clinical; D011379:Prognosis; D014178:Translocation, Genetic
BCL2; MYC; follicular lymphoma; grade 3; pediatric