Tehran University of Medical Sciences International Journal of Hematology-Oncology and Stem Cell Research 2008-2207 16 2 2022 04 03 94 102 EN Rui Almeida Department of Pathology, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal Carlos Abrantes Department of Anatomical Pathology, Hospital of the University of Coimbra (CHUC), Portugal Davide Gigliano Department of Pathology, Portuguese Oncology Institute of Porto, Porto, Portugal Rui Oliveira Department of Pathology, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal Paulo Teixeira Department of Pathology, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal Marta Viegas Molecular Pathology Laboratory, Instituto Português de Oncologia de Coimbra de Francisco Gentil, 3000-651 Coimbra, Portugal Ângelo Rodrigues Department of Pathology, Portuguese Oncology Institute of Porto, Porto, Portugal Maria Julião Department of Pathology, Coimbra Hospital and University Centre, CHUC, EPE, 3000-075, Coimbra, Portugal 2020 05 31 2022 01 03    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.   https://ijhoscr.tums.ac.ir/index.php/ijhoscr/article/view/1351 https://ijhoscr.tums.ac.ir/index.php/ijhoscr/article/download/1351/927