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

Virchows Arch. 2021 Jul;479(1):133-145. doi: 10.1007/s00428-021-03022-8. Epub 2021 Feb 2.

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.

Keywords: Blastoid; CDKN2A; Clonal evolution; MCL; MYC; Mantle cell lymphoma; P53; SOX11; TP53; TdT; Terminal deoxynucleotidyl transferase.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / genetics*
  • Child, Preschool
  • Chromosome Breakpoints*
  • Clonal Evolution
  • Comparative Genomic Hybridization
  • Cyclin D1 / genetics*
  • Cytogenetic Analysis
  • DNA Nucleotidylexotransferase / analysis
  • Diagnosis, Differential
  • Female
  • Gene Rearrangement*
  • Genetic Predisposition to Disease
  • Humans
  • Immunohistochemistry
  • Immunophenotyping
  • Lymphoma, Mantle-Cell / genetics*
  • Lymphoma, Mantle-Cell / immunology
  • Lymphoma, Mantle-Cell / pathology
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Phenotype
  • Predictive Value of Tests
  • Proto-Oncogene Proteins c-myc / genetics*

Substances

  • Biomarkers, Tumor
  • CCND1 protein, human
  • MYC protein, human
  • Proto-Oncogene Proteins c-myc
  • Cyclin D1
  • DNA Nucleotidylexotransferase