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Mantle cell lymphomas with concomitant MYC and CCND1 breakpoints are recurrently TdT positive and frequently show high-grade pathological and genetic features

2021; Springer Science+Business Media; Volume: 479; Issue: 1 Linguagem: Inglês

10.1007/s00428-021-03022-8

1432-2307

Sietse Aukema, Giorgio Alberto Croci, Susanne Bens, Kathrin Oehl‐Huber, Rabea Wagener, German Ott, Andreas Rosenwald, Philip M. Kluin, Eva van den Berg, Anneke Bosga-Bouwer, Mels Hoogendoorn, Eva Hoster, Iris Bittmann, Inga Nagel, Eva Maria Murga Penas, Markus Kreuz, Julia Bausinger, Wilfried Belder, Ilske Oschlies, Martin J.S. Dyer, Sandrine Jayne, Reiner Siebert, Wolfram Klapper,

Chronic Lymphocytic Leukemia Research

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.