Page 153 - Haematologica Vol. 107 - September 2022

ARTICLE - FL3B and simultaneous DLBCL
K. Koch et al.
DLBCL within individual patients/lymphomas. Similarly to previous studies,5,9 we found that a large number of cases of FL3B were associated with DLBCL at first diagnosis. Moreover, we found a pattern intermediate between fol- licular and diffuse growth endorsing the impression of a pathological continuum between FL3B and DLBCL. Fur- thermore, we showed that the molecular features of co- existing FL3B and DLBCL were homogeneous and that there was no molecular evidence of progression/trans- formation. In fact, the differences between follicular and diffuse growth - representing FL3B and DLBCL, respect- ively – were subtle and restricted to the features of the non-neoplastic microenvironment. Considering these findings it was not surprising to see that clinical features did not differ between patients with FL3B and those with FL3B+DLBCL. It seems reasonable to assume that FL3B represents a molecular and clinical continuum with DLBCL. Thus, FL3B+DLBCL does not reflect progression or transformation of the disease, suggesting that treatment should follow the same guidelines for FL3B and DLBCL. Of note, the subtype of IRF4 translocation-positive lym- phomas now recognized by the WHO classification was excluded from our analysis. However, large B-cell lym- phoma with IRF4 translocations shares features with FL3B such as histology (mostly presenting as FL3B and/or DLBCL),25 patients’ age (younger adults)10,26 and outcome (favorable).27 To what extent FL3B lacking IRF4 aberrations and large B-cell lymphoma with IRF4 translocations may in fact share pathogenic features needs to be addressed in future studies that might help to specify diagnostic criteria. Another interesting group of patients to analyze in the future might be those with FL3B at primary diagno- sis and DLBCL at relapse. However, this is hindered by the fact that only a small proportion of patients with FL3B re- lapse and of those who do only few undergo a second bi- opsy. This also holds true for our cohort, in which a second biopsy was only available for two patients. Moreover, a more detailed molecular analysis of FL3B and
References
1. WHO Classification of Tumors of Haematopoietic and Lymphoid Tissues. Revised 4th ed: International Agency for Reaserch on Cancer, 2018.
2. Hans CP, Weisenburger DD, Vose JM, et al. A significant diffuse component predicts for inferior survival in grade 3 follicular lymphoma, but cytologic subtypes do not predict survival. Blood. 2003;101(6):2363-2367.
3. Ganti AK, Weisenburger DD, Smith LM, et al. Patients with grade 3 follicular lymphoma have prolonged relapse-free survival following anthracycline-based chemotherapy: the Nebraska Lymphoma Study Group experience. Ann Oncol. 2006;17(6):920-927.
4. Dreyling M, Ghielmini M, Rule S, et al. Newly diagnosed and relapsed follicular lymphoma: ESMO clinical practice guidelines
FL3B+DLBCL, such as that applied in our current study, may provide a molecular genetic definition of FL3B inde- pendent of the histological detection of follicular growth. One could speculate that a molecular definition of FL3B might identify a molecular counterpart among DLBCL lacking a histopathologically detectable FL3B component but sharing clinical features.
Disclosures
AH has received travel expenses from Celgene and Roche. UD has received research funding from Amgen; has received honoraria and research funding from Celgen and Roche; has acted as a consultant for and received honoraria from AbbVie and Gilead; and has received honoria from Janssen. WK has received honoraria and research funding from Amgen, Regeneron, Hoffman-La Roche and Takeda.
Contributions
KK and WK designed the research project, KK, CH and JR generated and analyzed pathological and molecular data, AH and UD analyzed clinical data. KK, JR and WK wrote the manuscript. All authors read and agreed on the final version of the manuscript.
Acknowledgments
The authors would like to thank Dana Germer, Charlotte Botz von Drathen, Reina Zühlke-Jenisch and Lorena Vallés Uriarte for excellent technical support.
Funding
This work was supported by an intramural grant of the Medical Faculty of the University of Kiel to KK (F359991). The PETAL trial is funded by Deutsche Krebshilfe (grants n. 107592 and 110515), Amgen Germany, and Roche Pharma.
Data-sharing statement
Data will be shared according to ethical and administrative guidelines upon request for collaboration.
for diagnosis, treatment and follow-up. Ann Oncol.
2021;32(3):298-308.
5. Mustafa Ali M, Rybicki L, Nomani L, et al. Grade 3 follicular
lymphoma: outcomes in the rituximab era. Clin Lymphoma
Myeloma Leuk. 2017;17(12):797-803.
6. Shustik J, Quinn M, Connors JM, Gascoyne RD, Skinnider B,
Sehn LH. Follicular non-Hodgkin lymphoma grades 3A and 3B have a similar outcome and appear incurable with anthracycline-based therapy. Ann Oncol. 2010;22(5):1164-1169.
7. Kumar E, Pickard L, Okosun J. Pathogenesis of follicular lymphoma: genetics to the microenvironment to clinical translation. Br J Haematol. 2021;194(5):810-821.
8. Wahlin BE, Yri OE, Kimby E, et al. Clinical significance of the WHO grades of follicular lymphoma in a population-based
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