Page 15 - Haematologica Vol. 107 - September 2022

EDITORIAL
J.Y. Song
To be, or not 3B
Joo Y. Song
Department of Pathology, City of Hope National Medical Center, Duarte, CA, USA E-mail: josong@coh.org
doi:10.3324/haematol.2021.280263
Although follicular lymphoma (FL) is the most common, indolent non-Hodgkin B-cell lymphoma, grade 3B (FL3B) only accounts for 5-10% of cases of FL and is character- ized by follicles consisting exclusively of centroblasts.1 Ap- proximately half of the cases of FL3B also show a low-grade component (grade 1-2) or diffuse large B-cell lymphoma (DLBCL).2 Most consider FL3B to be aggressive and treat these cases as DLBCL with intense immunoche- motherapy such as rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP). How- ever, there are limited data on these cases from molecular and therapeutic standpoints since these cases are often excluded from clinical trials.
In this issue of Haematologica, Koch and colleagues3 help to shed light on this rare and aggressive disease by ana- lyzing cases of FL3B alone and FL3B together with DLBCL using a targeted sequencing panel and taking care to ex- clude cases of pediatric FL and cases with the IRF4 trans- location.4 The authors observed that 88% (14/16) of the cases of composite FL3B and DLBCL showed mutational variants shared by the FL3B component and DLBCL after macrodissection of these areas. In addition, the majority of the cases shared the same chromosomal abnormalities with BCL2, BCL6, and MYC rearrangements by fluor- escence in situ hybridization analysis. These findings are
Figure 1. Follicular lymphoma grade 3B and diffuse large B-cell lymphoma. Left: follicular lymphoma grade 3B (FL3B) with an expanded follicular dendritic cell meshwork highlighted with CD21. Right: diffuse large B-cell lymphoma (DLBCL) with sheets of large and atypical cells. Concurrent FL3B and DLBCL show shared mutations and translocations with KMT2D, CREBBP, BCL6, and BCL2.
Haematologica | 107 September 2022
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similar to those of other studies evaluating the genomic landscape of FL and its transformed state,5 as there were no specific recurrent mutations identified to predict transformation to DLBCL. Not surprisingly, the most fre- quent mutations that were shared by the FL3B and DLBCL components were CREBBP and KMT2D (Figure 1).
The next question is how do patients with FL3B respond to intense chemotherapy? In a subset of the patients with FL3B and FL3B plus DLBCL who were enrolled in the prospective randomized PETAL trial,6 analysis of overall and progression-free survival showed that, in this limited cohort of patients, the survival outcomes of these pa- tients were similar to those of patients with de novo DLBCL.
FL3B continues to be a difficult disease to analyze from genomic and clinical standpoints. The difficulties are due in part to the absence of these cases in large, prospective clinical trials, the heterogeneity of composite disease with low-grade FL or DLBCL, and issues with poor reproduci- bility of grading. Koch and colleagues3 show that the ge- nomic abnormalities in cases of concurrent FL3B and DLBCL are shared by the two components, further sup- porting the concept that FL3B may represent DLBCL and can be managed with aggressive immunochemotherapy in a manner similar to de novo DLBCL. The retained follicular