clinical and pathological features of double hit and triple hit high grade b cell lymphomas: a retrospective study from three portuguese tertiary centers

Background: high-grade b-cell lymphoma (hgbl) with rearrangements of myc and bcl2 and/or bcl6, called double and triple-hit lymphomas (dth-hgbl), are lymphoid malignancies with inferior outcomes when treated with standard chemotherapy. the identification of dth-hgbl cases is challenging, considering their variable clinical, morphologic, and immunohistochemical features. materials and methods: retrospective revision of medical data of patients diagnosed with dth-hgbl confirmed by fish, between january 2010 and january 2020, in three tertiary portuguese hospitals (coimbra hospital and university center, portuguese oncology institute – coimbra and portuguese oncology institute – porto). pathological features, morphology, and immunohistochemical profile were evaluated by at least two experienced pathologists in hematopoietic and lymphoid neoplasms. results: the cohort included 24 patients: 33.3% triple-hit, 58.3%, myc/bcl2 double-hit and 8.3% myc/bcl6 double-hit. there was no gender predominance, with a median age of 62.5±14.3y, 33.3% were diagnosed as nodal disease, and 66.7% as extranodal. morphologic features of dlbcl were present in 50% of cases, morphological features of both dlbcl and burkitt lymphoma (dlbcl/bl) in 45.8% and 4.2% of blastoid morphology. immunohistochemical evaluation, regarding the hans algorithm, revealed a germinal center (gc)/gc-like subtype in 83.3% of cases and a non-gc/non-gc-like subtype in 16.7%. myc was positive in 42.9% and the median proliferative index was 80±12.4%. conclusion: dth-hgbl has a very broad range of features. we consider that a cost-effective approach would be to perform cytogenetic analysis in dlbcl and dlbcl/bl cases with gc/gc-like subtype. myc and bcl2 immunohistochemistry can be useful to identify patients who may benefit from more aggressive therapies, but not as tools for case selection for fish.