Mediastinal B-cell lymphoma with MYC , BCL2 , and BCL6 rearrangements

Primary mediastinal B-cell lymphoma (PMBL) is a rare but aggressive form of non-Hodgkin lymphoma (NHL) that shares significant overlap with Diffuse large B-cell lymphoma (DLBCL). Double- (DH) and triple-hit (TH) lymphomas are aggressive B-cell lymphomas with translocations involving MYC + BCL2 or BCL6 and MYC + BCL2 + BCL6 , respectively. There are only 2 previous reports of DH in PMBL and no reports of TH. Here, we present the case of a 23-year-old female with post-treatment relapse of PMBL into a PMBL-TH, after initially presenting with MYC but without either BCL2 or BCL6 rearrangement. Immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and the Lymph3Cx gene expression assay were used to confirm the diagnosis. This case initiates the literature for PMBL-TH and expands the overall knowledge base regarding DH/TH in B-cell lymphomas. It also further emphasizes the utility of genetic and molecular assays in clinical identification of unique B-cell lymphoma subtypes when considering potential treatment courses.