Lymphoplasmacytic lymphoma associated with diffuse large B-cell lymphoma: Progression or divergent evolution?

PLoS One. 2020 Nov 12;15(11):e0241634. doi: 10.1371/journal.pone.0241634. eCollection 2020.

Abstract

Aim: Lymphoplasmacytic lymphoma (LPL) is an indolent mature B-cell-neoplasm with involvement of the bone marrow. At least 90% of LPLs carry MYD88-L265P mutation and some of them (~10%) transform into diffuse large B-cell-lymphoma (DLBCL).

Material and methods: Over the past 15 years we have collected 7 cases where the both LPL and DLBCL were diagnosed in the same patient. Clinical records, analytical data and histopathological specimens were reviewed. FISH studies on paraffin-embedded tissue for MYC, BCL2 and BCL6 genes were performed, as well as MYD88-L265P mutation and IGH rearrangement analysis by PCR. A mutational study was done by massive next generation sequencing (NGS).

Results: There were 4 women and 3 men between 36-91 years of age. Diagnoses were made simultaneously in 4 patients. In two cases the LPL appeared before the DLBCL and in the remaining case the high-grade component was discovered 5 years before the LPL. In 6 cases both samples shared the MYD88-L265P mutation. IGH rearrangement analysis showed overlapping features in two of 6 cases tested. Mutational study was evaluable in three cases for both samples showing shared and divergent mutations.

Conclusions: These data suggest different mechanisms of DLBCL development in LPL patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Clonal Evolution
  • Disease Progression
  • Female
  • Gene Rearrangement, B-Lymphocyte, Heavy Chain
  • Genetic Heterogeneity*
  • Humans
  • Lymphoma, Large B-Cell, Diffuse / genetics*
  • Lymphoma, Large B-Cell, Diffuse / pathology
  • Male
  • Middle Aged
  • Mutation, Missense
  • Myeloid Differentiation Factor 88 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-6 / genetics
  • Proto-Oncogene Proteins c-myc / genetics

Substances

  • BCL2 protein, human
  • BCL6 protein, human
  • MYC protein, human
  • MYD88 protein, human
  • Myeloid Differentiation Factor 88
  • Proto-Oncogene Proteins c-bcl-2
  • Proto-Oncogene Proteins c-bcl-6
  • Proto-Oncogene Proteins c-myc

Grants and funding

This work was supported by grants from the Instituto de Salud Carlos III (ISCIII) of the Spanish Ministry of Economy and Competence (MINECO, RTICC ISCIII and CIBERONC) (SAF2013-47416-R, RD06/0020/0107-RD012/0036/0060 and Plan Nacional I+D+I: PI16/01294 and PIE15/0081) and the Madrid Autonomous Community. Dr. Piris is being sponsored by TAKEDA. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.