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

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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
JournalVirchows Archiv
DOIs
Publication statusAccepted/In press - 2021
Externally publishedYes

Keywords

  • Blastoid
  • CDKN2A
  • Clonal evolution
  • Mantle cell lymphoma
  • MCL
  • MYC
  • P53
  • SOX11
  • TdT
  • Terminal deoxynucleotidyl transferase
  • TP53

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology

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