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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

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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 (MYCR+, n = 15, MYCR−, 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.

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Funding

The research of W.K. and R.S. on MYC positive lymphomas is supported in the framework of a MMML-MYC-SYS grant (036166B) by the German Ministry of Science and Education (BMBF). Former grant support of MMML by the Deutsche Krebshilfe (2003–2011) and the support of the technical staff of the Institutes of Human Genetics in Kiel and Ulm are gratefully acknowledged. Work in Leicester supported by Cancer Research UK in conjunction with the UK Department of Health on an Experimental Cancer Medicine Centre grant [C10604/A25151].

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S.M.A., G.A.C., R.S. and W.K. designed the research; G.O., A.R., E.v/d B., A.B-B., M.H., I.B., E.H., M.K., W.B. S.J. and M.J.S.D. provided clinical, genetic and/or pathological data and samples; S.M.A, R.W., S.B., K.O-H., M.K., J.B., I.N., E.M.P. and R.S. performed (molecular)cytogenetic, molecular and/or bio-informatical analyses; G.A.C., P.K., I.O. and W.K. performed histopathological review; S.M.A., G.A.C., R.S. and W.K. wrote the manuscript; all authors approved the final version of the manuscript.

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Correspondence to Sietse M. Aukema, Reiner Siebert or Wolfram Klapper.

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The study was conducted in accordance with the recommendations of the ethics board of the Medical Faculty, University of Kiel, numbers D425/03, D447/10 and amendment from 09.03.2010 which includes that based on the historic nature of several cases a written informed consent on participation and publication could not be obtained.

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Aukema, S.M., Croci, G.A., Bens, S. et al. Mantle cell lymphomas with concomitant MYC and CCND1 breakpoints are recurrently TdT positive and frequently show high-grade pathological and genetic features. Virchows Arch 479, 133–145 (2021). https://doi.org/10.1007/s00428-021-03022-8

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