TRIPLE POSITIVE (CD10+BCL6+MUM1+) DIFFUSE LARGE B‐CELL LYMPHOMAS IN ADULTS ARE A HETEROGENEOUS GROUP ENRICHED IN LARGE B‐CELL LYMPHOMAS WITH IRF4 REARRANGEMENT

Introduction: Gene expression profiling (GEP) divides DLBCL according to the cell of origin (COO) into GCB, ABC and unclassifiable (UNC), exhibiting different mutational profiles. The Hans algorithm (HA), a surrogate of GEP, classifies cases expressing CD10, BCL6 and MUM1 as GCB but it is not clear whether all these cases correspond to GCB-type. Accordingly, LBCL with IRF4 rearrangement (LBCL-IRF4) usually expresses a GCB phenotype (CD10+, BCL6+) together with strong MUM1/IRF4. The aim of this study was to characterize the molecular heterogeneity of DLBCL triple positive (CD10 + BCL6 + MUM1+) in adults. Methods: Fifty-five triple positive DLBCL were investigated with FISH (BCL2, BCL6, MYC, IRF4, IGH, IGL), NGS targeted sequencing (SureSelectXT, 66 genes), COO using Nanostring and/or HTG molecular, and copy number (CN) analysis using Oncoscan platform. The mutational subtype was defined using the algorithm by Wright et al (Cancer Cell 2020). Results: According to GEP, 32/54 (59%) cases were classified as GCB, 17/54 cases (32%) as ABC, and 5/54 (9%) UNC. Based on FISH analyses 3 groups were recognized. Group 1 included 15/55 cases (27%) without translocations. Eight cases (54%) were GCB-, whereas 7 cases ABC-type (46%). The MCD mutational profile predominated in this group (6/12; 50%). Group 2 included 11/55 cases (20%) with isolated IRF4 alterations; 5 cases each were sub-classified either as GCB or ABC. This group was characterized by one or multiple IRF4 mutations (82%) and frequent MYD88, CARD11 and CD79B mutations. In two cases no IRF4 break was identified; however, these two cases had a light chain IG break and multiple IRF4 mutations. Group 3 included 29/55 cases (53%) with one or several translocations in BCL2/BCL6/MYC/IGH. Two of these cases had a complex FISH constellation with BCL2 and/or BCL6 together with IRF4 translocation. In this group predominated the GCB-type (19/29; 66%) and the EZB (8/25; 32%) mutational profile. Oncoscan was performed in 7 cases of LBCL-IRF4. A total of 118 genetic alterations were identified (mean: 17 CNA/case). The comparison between LBCL-IRF4 in adults and previously published data in pediatric population (figure) showed no difference in terms of recurrent CN regions; however, adult cases showed higher genetic complexity (17 vs 6.25 alt/case; P = 0.33) and more often ABC COO (P = 0.05). Mutational comparison showed higher mutational load in adult cases (10.6 vs 4.7 mutation/case; P = 0.004) and higher frequency of KMT2D, MYD88 and BTG2 mutations (P < 0.05). Keywords: Pathology and Classification of Lymphomas No conflicts of interests pertinent to the abstract. SESSION 11: HODGKIN LYMPHOMA