1. Mantle cell lymphomas with concomitant MYC and CCND1 breakpoints are recurrently TdT positive and frequently show high-grade pathological and genetic features
- Author
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Kathrin Oehl-Huber, Sandrine Jayne, Julia Bausinger, Anneke G. Bosga-Bouwer, Ilske Oschlies, Wolfram Klapper, Sietse M. Aukema, Rabea Wagener, Andreas Rosenwald, Eva Hoster, Wilfried Belder, Markus Kreuz, Philip M. Kluin, Iris Bittmann, Reiner Siebert, Giorgio A. Croci, Eva Maria Murga Penas, Inga Nagel, Martin J. S. Dyer, Mels Hoogendoorn, German Ott, Eva van den Berg, and Susanne Bens
- Subjects
0301 basic medicine ,Male ,Proliferation index ,Follicular lymphoma ,MYC ,Lymphoma, Mantle-Cell ,Blastoid ,Chromosome Breakpoints ,0302 clinical medicine ,CDKN2A ,hemic and lymphatic diseases ,Cyclin D1 ,TP53 ,Aged, 80 and over ,Gene Rearrangement ,Comparative Genomic Hybridization ,General Medicine ,Middle Aged ,Immunohistochemistry ,Phenotype ,030220 oncology & carcinogenesis ,Child, Preschool ,Cytogenetic Analysis ,Female ,TdT ,Biology ,Terminal deoxynucleotidyl transferase ,Pathology and Forensic Medicine ,Immunophenotyping ,Clonal Evolution ,Diagnosis, Differential ,Proto-Oncogene Proteins c-myc ,03 medical and health sciences ,DNA Nucleotidylexotransferase ,Predictive Value of Tests ,SOX11 ,medicine ,Biomarkers, Tumor ,Humans ,Genetic Predisposition to Disease ,Molecular Biology ,Aged ,P53 ,Mantle cell lymphoma ,Lymphoblastic lymphoma ,MCL ,Cell Biology ,medicine.disease ,biology.organism_classification ,Lymphoma ,030104 developmental biology ,Cancer research ,PAX5 ,Neoplasm Grading - Abstract
Chromosomal breakpoints involving the MYC gene locus, frequently referred to as MYC rearrangements (MYC - R+), are a diagnostic hallmark of Burkitt lymphoma and recurrent in many other subtypes of B-cell lymphomas including follicular lymphoma, diffuse large B-cell lymphoma and other high-grade B-cell lymphomas and are associated with an aggressive clinical course. In remarkable contrast, in MCL, only few MYC - R+ cases have yet been described. In the current study, we have retrospectively analysed 16 samples (MYC - R+, n = 15, MYC - R-, n = 1) from 13 patients and describe their morphological, immunophenotypic and (molecular) genetic features and clonal evolution patterns. Thirteen out of fifteen MYC - R+ samples showed a non-classical cytology including pleomorphic (centroblastic, immunoblastic), anaplastic or blastoid. MYC translocation partners were IG-loci in 4/11 and non-IG loci in 7/11 analysed cases. The involved IG-loci included IGH in 3 cases and IGL in one case. PAX5 was the non-IG partner in 2/7 patients. The MYC - R+ MCL reported herein frequently displayed characteristics associated with an aggressive clinical course including high genomic-complexity (6/7 samples), frequent deletions involving the CDKN2A locus (7/10 samples), high Ki-67 proliferation index (12/13 samples) and frequent P53 expression (13/13 samples). Of note, in 4/14 samples, SOX11 was not or only focally expressed and 3/13 samples showed focal or diffuse TdT-positivity presenting a diagnostic challenge as these features could point to a differential diagnosis of diffuse large B-cell lymphoma and/or lymphoblastic lymphoma/leukaemia.
- Published
- 2020