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Cell of origin in diffuse large B-cell lymphoma in systemic lupus erythematosus: molecular and clinical factors associated with survival
  1. Basile Tessier-Cloutier1,
  2. David DW Twa2,
  3. Eva Baecklund3,
  4. Randy Gascoyne4,5,
  5. Nathalie A Johnson6,
  6. Carin Backlin7,
  7. Diane L Kamen8,
  8. Ann E Clarke9,
  9. Rosalind Ramsey-Goldman10,
  10. Jennifer LF Lee11,
  11. Pedro Farinha4,5 and
  12. Sasha Bernatsky11,12
  1. 1Anatomical Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada
  2. 2Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
  3. 3Department of Medical Sciences, Uppsala Universitet, Uppsala, Sweden
  4. 4Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada
  5. 5Pathology Department and Centre for Lymphoid Cancer, British Columbia Cancer Agency, Vancouver, British Columbia, Canada
  6. 6Department of Medicine, Sir Mortimer B Davis Jewish General Hospital, Montreal, Québec, Canada
  7. 7Department of Rheumatology and Immunology, Medical University of South Carolina, Charleston, South Carolina, USA
  8. 8Medicine, Medical University of South Carolina, Charleston, South Carolina, USA
  9. 9University of Calgary, Calgary, Alberta, Canada
  10. 10Medicine/Rheumatology, Northwestern University, Chicago, Illinois, USA
  11. 11Division of Clinical Epidemiology, McGill University Health Centre, Montreal, Québec, Canada
  12. 12Department of Medicine, McGill University, Montreal, Québec, Canada
  1. Correspondence to Dr Sasha Bernatsky; sasha.bernatsky{at}mcgill.ca

Abstract

Background SLE is associated with increased risk of diffuse large B-cell lymphoma (DLBCL). DLBCL is routinely classified by cell of origin (COO), with germinal centre B-cell (GCB) being more common and indicating better prognosis in the general population. We studied COO subtyping in patients with SLE diagnosed with DLBCL and their survival.

Patients and methods We evaluated 20 cases of SLE with DLBCL. Immunohistochemistry analysis was performed (BCL2, MYC, BCL6, CD10, CD20, FOXP1, GCET1, MUM1) in tissue microarrays. We examined associations between molecular and clinical features, including overall survival.

Results Of the 20 DLBCL SLE cases, 12/20 cases (60%) were classified as non-GCB using Hans or Choi algorithms. MYC and BCL2 protein expression was positive in 6/20 (30%) and 8/20 (40%) SLE cases, respectively, with 2/20 (10%) co-expressing both markers. Seven (7/20) had only extranodal involvement at DLBCL diagnosis. As expected, non-GCB cases had worse survival. Cases presenting exclusively with extranodal disease were associated with shorter SLE duration and better survival despite higher BCL2 protein expression.

Conclusions We present novel data characterising DLBCL in SLE. Sixty per cent of the DLBCL in patients with SLE were non-GCB. The nodal and extranodal distribution in SLE was similar to what is known in the general population, but extranodal disease occurred more often with short SLE duration and was associated with longer overall survival. More research on cancer in SLE is the key to further understanding the complex interplay between cancer and the immune system.

  • systemic lupus erythematosus
  • diffuse large b-cell lymphoma
  • epidemiology
  • immunohistochemistry
  • cell-of-origin

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

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Footnotes

  • Presented at Preliminary data on this work were previously presented at the American College of Rheumatology 2018 Annual Meeting. Abstract number 710 (https://acrabstracts.org/abstract/an-analysis-of-cell-of-origin-in-diffuse-large-b-cell-lymphoma-in-systemic-lupus-erythematosus-including-molecular-and-clinical-factors-associated-with-survival/).

  • Contributors SB, AEC, BT-C and PF designed the research study. PF, RG, EB, NJ, CB, DLK, AEC, RR-G, JL and SB contributed essential clinical data and tumour tissue. BT-C and PF performed the pathology review and immunohistochemistry scoring. BT-C, PF, DT and SB analysed the data. All authors contributed to the interpretation of results and writing of the manuscript. All authors approved the manuscript.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient consent for publication Obtained.

  • Ethics approval The study was approved by the Research Ethics Board of the McGill University Health Centre (GEN-06-031) and the participating institutions.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement Data are available upon reasonable request.

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