Page 145 - Haematologica Vol. 107 - September 2022

ARTICLE - Non-Hodgkin Lymphoma
Follicular lymphoma grade 3B and diffuse large B-cell lymphoma present a histopathological and molecular continuum lacking features of progression/ transformation
Karoline Koch,1 Julia Richter,1 Christoph Hänel,1 Andreas Hüttmann,2 Ulrich Dührsen2 and Wolfram Klapper1
1Department of Pathology, Hematopathology Section, University Hospital Schleswig- Holstein, Kiel and 2Department of Hematology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
Abstract
The sole distinguishing feature of follicular lymphoma grade 3B and diffuse large B-cell lymphoma is the growth pattern assessed by histopathology. Diffuse growth defines diffuse large B-cell lymphoma but the clinical relevance of this finding when occurring in follicular lymphoma grade 3B is uncertain. To address this issue, individual and coexisting follicular lymphoma grade 3B and diffuse large B-cell lymphoma were separated and analyzed for immunophenotype and molecular genetic features by fluorescence in situ hybridization, targeted sequencing and gene expression profiling. Clinical features of follicular lymphoma grade 3B with and without coexisting diffuse large B-cell lymphoma were studied in homogeneously treated patients from a prospective randomized trial. Follicular lymphoma grade 3B and diffuse large B-cell lymphoma frequently show an intermediate growth pattern and/or occur simultaneously in the same tissue at the time of initial di- agnosis. When occurring simultaneously follicular lymphoma grade 3B and diffuse large B-cell lymphoma do not differ significantly for genetic aberrations or phenotype but have distinct gene expression features reflecting a divergent micro- environment. Follicular lymphoma grade 3B with and without coexisting diffuse large B-cell lymphoma do not differ for major clinical parameters such as International Prognostic Index, response to immuno-chemotherapy, progression or over- all survival. Follicular lymphoma grade 3B and simultaneous diffuse large B-cell lymphoma are molecularly homogenous. Histological detection of diffuse large B-cell lymphoma is not associated with features of a more aggressive disease and does not reflect transformation or progression of follicular lymphoma grade 3B.
Introduction
Follicular lymphoma (FL) is one of the most frequent lym- phoma entities in central Europe and Northern America and is subdivided into “grades” by morphology.1 Follicular lym- phoma grades 1, 2 and 3A are composed of centrocytes and centroblasts and distinguished by centroblast content whereas FL grade 3B (FL3B) consists exclusively of centro- blasts.1 Since the cytomorphology of FL3B is identical to that of diffuse large B-cell lymphoma (DLBCL), the sole dis- tinguishing feature of FL3B and DLBCL is the growth pattern assessed by histopathology which is follicular in FL3B and diffuse in DLBCL. Once the neoplastic cells in FL3B display areas of diffuse growth the lymphoma fulfills the diagnostic
criteria of DLBCL according to the World Health Organiza- tion (WHO) classification.1 Thus, diffuse areas of FL3B are considered “transformation” and this feature has been sug- gested to be of clinical significance.2,3 Unlike FL grades 1, 2 and 3A, FL3B is considered an aggressive lymphoma by most clinical research groups and treated in the same way as DLBCL4 despite the fact that under rituximab-containing poly-chemotherapy (e.g., rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone [R-CHOP]) outcomes might not be very different between FL3A and FL3B.5,6 Transformation of FL grades 1, 2 and 3A to DLBCL has been shown to be associated with major changes in molecular pathogenic pathways and is well established to reflect a true “transformation” with change in clinical behavior and
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Correspondence: K. Koch karoline.koch@uksh.de
Received: Accepted: Prepublished:
June 1, 2021. November 11, 2021. January 13, 2022.
https://doi.org/10.3324/haematol.2021.279351
©2022 Ferrata Storti Foundation Published under a CC BY-NC license