Clinical features, prognosis and therapy in FL3A

K. Koch from the University Hospital Schleswig–Holstein, Kiel, Germany, and colleagues published results on a study looking to understand the histopathological and clinical features of Grade 3 Follicular Lymphoma (FL3) in patients from several German clinical trials. The findings were first published ahead of print in the Annals of Oncology in April 2016. FL3A often co-exists with Grade 1 and 2 FL (FL1/2) and it is distinct from FL3B. FL1/2 and MYC breaks can be used as prognostic factors to identify subgroups within FL3A. The use of first-line immunochemotherapy allows long-lasting remissions and survival for FL3 patients.

  • FL3A is biologically related to FL1/2 while FL3B is a different entity
  • 5-year PFS FL3A vs FL3B = 61% vs 71% (P = 0.71), 5-year OS = 84% vs 79% (P = 0.98)
  • Survival curve for pure FL3A forms a plateau
  • FL3A with FL1/2 component showed poorer outcome (HR 4.51, P = 0.053)
  • 5-year PFS of FL3A harboring t(14;18) vs t(14;18) negative = 60% vs 85% (P = 0.052)
  • Localized FL3A negative t(14;18) resembled pediatric FL and had better outcome
  • 5-year PFS of pediatric FL3A vs non-pediatric FL3B = 100% vs 60% (P = 0.082)
  • MYC breaks were associated with a poorer outcome for combined FL3A, pure FL3A and FL3B patients

A corresponding editorial by Sorigue et al. provided further perspective for these findings as well as some limitations. Firstly, they suggested that the findings published by Koch et al. were difficult to compare with previous findings. Secondly, recent large studies have shown conflicting results on the use of immunochemotherapy for front-line therapy in FL3 patients. Additionally, the prognostic uncertainty makes it difficult to determine the best front-line therapy for FL3. Finally, Sorigue et al., concluded that the decision of choosing the best front-line treatment for FL3 is more complex due to lack of evidence and prognostic uncertainty.


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.


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.

  1. Koch K. et al. 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. Annals of Oncology. 2016 Jul; 27(7):1323–1329. doi: 10.1093/annonc/mdw185. Epub 2016 Apr 26.
  2. Sorigue M. et al. The clinical dilemma of grade 3 follicular lymphoma. Annals of Oncology. 2016 Oct; 27(10):1974. doi: 10.1093/annonc/mdw284. Epub 2016 Aug 8.


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