Blood 2015 :; published ahead of print August 25, 2015
Robert Kridel, Anja Mottok, Pedro Farinha, Susana Ben-Neriah, Daisuke Ennishi, Yvonne Zheng, Elizabeth A. Chavez, Hennady P. Shulha, King Tan, Fong Chun Chan, Merrill Boyle, Barbara Meissner, Adele Telenius, Laurie H. Sehn, Marco A. Marra, Sohrab P. Shah, Christian Steidl, Joseph M. Connors, David W. Scott, Randy D. Gascoyne

In this study Kriedel and Mottok et al have assessed the cell of origin of transformed follicular lymphomas (TFL) and their relationship to the antecedent follicular lymphomas using a cohort of 126-155 specimens. They showed that grade 3A, BCL6 translocation, IRF4 expression and lack of CD10 staining were associated with early transformation but only IRF4 turned out to have independent predictive value in multivariate analysis. Moreover MYC was more commonly translocated, and IRF4 more commonly expressed in TFLs than in antecedent FL. Their results also showed that the outcome of patients with a composite histology (with a mixture in varying proportions of FL and DLBCL in the same biopsy) at time of transformation was better than the outcome of patients with a pure DLBCL morphology or B cell lymphoma with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma (BCLU). Double-hit status was found in 24% of all TFLs, and in 19%, 13% and 100% of TFLs with a DLBCL, composite or BCLU morphology. Although not statistically significant double-hit TFL cases had inferior survival post-transformation. The majority of their TFL cases were of the germinal-centre B-cell-like subtype (80%), 16% of the cases however was of the activated B-cell-like subtype and were commonly negative for BCL2 translocation and preferentially arised from BCL2 translocation-negative and/or IRF4-expressing FLs. 6 out of 13 BCL2 translocation-negative FLs however were seen to transform into the GCB subtype. Mutations in CD79B and MYD88 were recurrent in ABC-TFLs.  They hence concluded that TFLs displayed molecular heterogeneity in itself as well as with regard to its relationship to the antecedent FL and suggested that due to this inter-patient heterogeneity treatment approaches may need to be tailored with regard to the  underlying biology in order to reverse the adverse outcome that is currently associated with transformation.