A retrospective study of MYC rearranged diffuse large B-cell lymphoma in the context of the new WHO and ICC classifications
Dima El‐Sharkawi, Amit Sud, Catherine Prodger, Jahanzaib Khwaja, Rohan Shotton, Brian Hanley, Victoria Peacock, Ying Ying Peng, Anita Arasaretnam, Sarkhara Sharma, Frances Aldridge, Bhupinder Sharma, Andrew Wotherspoon, Betty Cheung, Corinne De Lord, Rosalynd Johnston, Shireen Kassam, Ruth Pettengel, Kim Linton, Paul Greaves, Lucy Cook, Kikkeri N. Naresh, Kate Cwynarski, Toby A. Eyre, Ian Chau, David Cunningham, Sunil Iyengar
Abstract
Diffuse large B-cell lymphoma (DLBCL) is an aggressive but biologically heterogenous Non-Hodgkin Lymphoma (NHL). Clinical prognostic scores such as the International Prognostic Index (IPI) are established predictors of outcome. There is however significant interest in using genomics to advance risk prediction as well as inform precision medicine strategies [ 1 , 2 , 3 , 4 , 5 , 6 , 7 ]. While genomic classification is evolving, chromosomal rearrangements involving the MYC, BCL2 and BCL6 are now widely tested for at diagnosis using fluorescence in situ hybridisation (FISH). Patients with MYC rearrangements (MYCR) have inferior outcomes and those with MYCR and concomitant translocations of BCL2 or BCL6 or both have particularly poor outcomes. The 2016 revision of the World Health Organisation (WHO) classification of haematological neoplasms subsequently categorised these lymphomas as high grade B-cell lymphomas (HGBL) with MYC, BCL2 and /or BCL6 rearrangements [ 8 ]. However, the recent 2022 iteration of the WHO classification excludes MYC-BCL6 rearranged cases from this category as these lymphomas are genetically heterogenous and distinct when compared to the MYC-BCL2 + /− BCL6 rearranged cases [ 9 , 10 ]. In comparison, the simultaneously released International Consensus Classification (ICC), while also recognising the distinct biology in MYC-BCL6 rearranged double hit (DH) cases, retains these cases as a sub-category on the basis that some studies have recorded poor outcomes in these patients [ 11 ].