Dr. Chen Yang joined the faculty of the University of Michigan’s Department of Pathology and Department of Pediatrics in July 2020. He currently holds the positions of Director of the MMGL Molecular Genetics Lab and Associate Director of the Clinical Cytogenetics Lab. Dr. Yang earned his medical degree from Tongji Medical College at Huazhong University of Science and Technology and went on to earn a master’s degree in pathology at Peking Union Medical College. He pursued his Ph.D. program at the University at Buffalo, focusing on eukaryotic basal transcription from 2005 – 2010. Subsequently, he completed a postdoctoral fellowship focusing on cancer research from 2010 – 2015 and received clinical ABMGG fellowship training in Laboratory Genetics and Genomics (LGG) from 2017 – 2020 at Virginia Commonwealth University. Since joining the faculty at Michigan Medicine, Yang has focused on clinical laboratory testing for both constitutional genetic disorders and genetic abnormalities of cancer.
Chen Yang, Chen Yang, Jiong Yang, Alysia Sanchez, Hong Xiao, Turquessa Brown-Krajewski, Anamarija Perry, Lina Shao
Department of Pathology, University of Michigan, Ann Arbor, MI, United States
The 5th edition of WHO classification and the 2022 International Consensus Classification of mature lymphoid neoplasms have reframed the double-hit lymphoma as high-grade B-cell lymphoma (HGBCL) with MYC and BCL2 rearrangements (HGBCL-MYC/BCL2). This aggressive lymphoma is relatively rare (4-10% of large/HGBCL), mostly found in older adults, and associated with poor outcomes. There are no reliable morphologic or immunophenotypic criteria to predict HGBCL-MYC/BCL2. Therefore, it is recommended to evaluate MYC and BCL2 translocation status for all large/HGBCL to enable modified management, including CAR-T cell therapy, or targeted clinical trial. The most common rearrangements leading to HGBCL-MYC/BCL2 are concurrent translocations t(8;14)(q24;q32) and t(14;18)(q32;q21) involving separate IGH alleles on both chromosome 14 homologs. Three-way translocation t(8;14;18) has been reported as a rare mechanism leading to the rearrangement of MYC and BCL2 with a single IGH locus. While the IGH::MYC fusion may be obvious due to the apparently classic der(14)t(8;14) from karyotyping, the IGH::BCL2 fusion is challenging due to the translocation of IGH::BCL2 to the MYC locus. Here, we report two HGBCL cases containing complex karyotypes with t(8;14;18), one with concurrent follicular lymphoma 3A and the other without. Metaphase FISH studies in both cases showed the IGH::MYC and IGH::BCL2 fusions on the same der(8) and confirmed the rearrangements of MYC and BCL2 with a single IGH locus due to sequential t(14;18)(q32;q21) followed by a translocation between chromosome 8 and der(14)t(14;18). The presence of t(8;14;18) in HGBCL warrants FISH confirmation for the accurate diagnosis of HGBCL-MYC/BCL2.