Page 152 - Haematologica Vol. 107 - September 2022

ARTICLE - FL3B and simultaneous DLBCL
K. Koch et al.
FL grades 1 and 2 compared to FL grade 3A and FL3B. In- itially, the grades of FL were thought to reflect a multistep process of tumor progression in analogy to grades of dif- ferentiation in solid tumors.23 However, there are several findings suggesting that at least a large fraction of FL3B cases are not a progressive form of FL grades 1, 2 and 3A. First, unlike FL grades 1, 2 and 3A, FL3B is diagnosed more frequently in younger patients, suggesting a unique patho- genesis.10,21 Second, molecular studies, e.g. on chromoso- mal translocations show, a much lower frequency of aberrations involving BCL2 and a higher frequency of BCL6 translocations in FL3B than in FL grades 1, 2, and 3A.9,11,13,24
Third, FL3B often co-exists with a DLBCL at initial diag- nosis whereas transformation of indolent FL grades 1, 2 and 3A mostly occurs at a later stage of the disease.5,9 Fourth, FL3B rarely follows or co-exists with FL grades 1, 2 and 3A, again suggesting differences in pathogenic path- ways.9
In the current study we analyzed an aspect of FL3B biol- ogy not addressed by previous studies. We aimed to understand whether the loss of follicular growth indicates molecular and clinical progression/transformation. To the best of our knowledge, this is the first study specifically analyzing the intratumoral heterogeneity of FL3B and
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Figure 3. Kaplan-Meier survival estimates for progression free (A) and overall survival (B) of patients with follicular lymphoma grade 3B with or without diffuse large B- cell lymphoma. Patients with diffuse large B-cell lymphoma (DLBCL) treated in the same trial are shown as a control (see Online Supplementary Table S3). As patients with activated B-cell or germinal center B-cell DLBCL did not differ significantly regarding progression-free survival and overall survival these subgroups were not differentiated.