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LYMPHOMA

IgM-secreting diffuse large B-cell lymphoma: results of a multicentre clinicopathological and molecular study

Leukemia volume 36, pages 2719–2723 (2022)Cite this article

Subjects

Recently we defined as IgM-secreting a subset of diffuse large B-cell lymphoma (IgMs-DLBCL) which showed a serum IgM paraprotein (PP) and the cytoplasmic expression of the same subtype of heavy and light chains [1]. The expression of an IgM B-cell receptor has been mostly reported in activated B-cell-like type (ABC-type) DLBCL with extra-nodal localization, and recurrent MYD88 and CD79B gene mutations [2]. However, only a minority of these secrete an IgM PP [1]. Indeed, the progression from a mature B-cell to an antibody-secreting-cell (ASC) is a finely regulated process, that occurs following the adaptive immune response to an antigen, by silencing the B-cell program and activating the ASC one [3]. We previously reported [1], IgMs-DLBCL was characterized by poor prognostic features and outcome, the PP was mostly present at low concentration, and it disappeared soon after starting treatments. In relapsing patients, the PP was not always detectable, presumably due to clonal evolution. Previously, Maurer et al. [4] showed that 14% of DLBCL have an altered k/λ ratio in the serum, while Jardin et al. [5] reported that an abnormal IgMκ/IgMλ serum ratio was associated with poor outcomes in DLBCL. Currently, the pathobiological features of IgMs-DLBCL are ill-defined [1, 5] and the prognostic impact of IgM PP versus other PP (OP) remains to be addressed [6, 7]. Herein we report the clinicopathological and molecular characterization of the largest multicentre series of IgMs-DLBCL described so far.

This retrospective and comparative study enroled adult DLBCL patients with an associated IgM PP or OP, who were diagnosed between 01/01/2010 and 31/07/2018. Subjects who transformed from a low-grade non-Hodgkin lymphoma to DLBCL and who were treatment-naïve were also included. All patients were—assessed for serum PP by immunofixation prior to starting treatment. Of the 20 Italian clinical centres involved in the study, 13 belonged to the Lazio Region Lymphoma-Network (ReLLi). This network, starting from 01/01/2013, recorded all consecutive newly-diagnosed lymphomas in a web-based regional registry. The reference group (REF), composed of DLBCL diagnosed between 01/01/2013 and 31/12/2016, without an associated serum PP (Table 1s), was retrieved from the ReLLI registry (data last accessed on 31/01/2019).

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Fig. 1: Overall (OS) and progression free (PFS) survival in IgMs-DLBCL, OP and REF DLBCL subsets.

Data availability

All the dataset of this study is embedded in the supplementary materials.

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Funding

Ateneo 2018, Sapienza University, Rome, Italy.

Author information

Authors and Affiliations

  1. Fondazione Policlinico Tor Vergata, University Hospital, Rome, Italy

    M. Christina Cox, Maria Cantonetti, Livio Pupo & Cristiano Tesei

  2. Fondazione Italiana Linfomi, Alessandria, Italy

    Luigi Marcheselli

  3. Department of Clinical and Molecular Medicine, Sapienza University, Sant’Andrea University Hospital, Rome, Italy

    Giorgia Scafetta, Sabrina Pelliccia, Gianluca Lopez, Stefania Scarpino, Giuseppina Pepe, Luigi Ruco & Arianna Di Napoli

  4. University of Verona, Verona, Italy

    Carlo Visco

  5. Università Cattolica del Sacro Cuore, Policlinico Agostino Gemelli, Roma, Italy

    Stefan Hohaus, Eleonora Alma & Luigi M. Larocca

  6. Campus Biomedico, Rome, Italy

    Ombretta Annibali & Antonella Bianchi

  7. Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Meldola, Italy

    Gerardo Musuraca & Silvia Asioli

  8. Azienda Ospedaliera universitaria Senese, Siena, Italy

    Alberto Fabbri & Lorenzo Leoncini

  9. Chimomo department, university of Modena and Reggio Emilia, Modena, Italy

    Robel Papotti

  10. Policlinico Umberto I University Hospital, Rome, Italy

    Luigi Petrucci

  11. Ospedale Santa Maria delle Croci, Ravenna, Italy

    Monica Tani

  12. Azienda Ospedaliera San Camillo, Rome, Italy

    Roberta Battistini

  13. Azienda USL, Piacenza, Italy

    Annalisa Arcari

  14. Hematology Ausl IRCCS of Reggio Emilia & Chimomo department, university of Modena and Reggio Emilia, Reggio Emilia, Italy

    Stefano Luminari

  15. Ospedale San Bortolo, Azienda USSL 8, Vicenza, Italy

    Giuseppe Carli & Emanuele S. G. D’amore

  16. IRCCS Regina Elena National Cancer Institute, Rome, Italy

    Francesco Marchesi

  17. Azienda Ospedaliera Universitaria, Parma, Italy

    Francesca Re

  18. Azienda Ospedaliera, Viterbo, Italy

    Fiammetta Natalino

  19. Azienda Ospedaliera San Giovanni, Rome, Italy

    Paola Anticoli-Borza

  20. Azienda Ospedaliera Universitaria, Latina, Italy

    Natalia Cenfra

  21. Azienda Ospedaliera, Frosinone, Italy

    Alessandro Andriani

  22. Azienda Ospedaliera Sant’Eugenio, Rome, Italy

    Elisabetta Abruzzese

Authors
  1. M. Christina Cox
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Contributions

MCC: study concept, and project supervision, enrolment of patients, data collection, data analysis, preparation of the manuscript. LM: study concept, Statistical analysis, preparation of the manuscript. GS: molecular and pathological analysis, data collection, preparation of the manuscript . CV: enrolment of patients, data collection, data analysis, preparation, and revision of the manuscript. SH: enrolment of patients, data collection, data analysis, preparation, and revision of the manuscript. OA: enrolment of patients, data collection, data analysis, preparation, and revision of the manuscript. GM: enrolment of patients, data collection, data analysis, preparation, and revision of the manuscript. AF: enrolment of patients, data collection, data analysis, preparation and revision of the manuscript. MC: enrolment of patients, data collection, data analysis,preparation of the manuscript. RP: Next Generation sequencing supervision, preparation ofthe manuscript. LP: enrolment of patients, data collection, preparation of themanuscript. MT: enrolment of patients, data collection, preparation of the manuscript. RB: enrolment of patients, data collection, preparation of the manuscript. AA: enrolment of patients, data collection, preparation of the manuscript. SL: enrolment of patients, data collection, preparation of the manuscript. SP: enrolment of patients, data collection & analysis, preparation of the manuscript. EA: enrolment of patients, data collection, preparation of the manuscript. LP: enrolment of patients, data collection, preparation of the manuscript. SS: FISH analysis, data collection, preparation of the manuscript. GC: enrolment of patients, data collection, preparation of the manuscript. FM: enrolment of patients, data collection, preparation and revision of the manuscript. FR: enrolment of patients, data collection, preparation of the manuscript. EDA: FISH and histological diagnosis, preparation of the manuscript. LML: histological diagnosis, data collection, preparation of the manuscript. AB: histological diagnosis, data collection, preparation of the manuscript. GL: next generation sequencing and sanger analysis, data collection, preparation of the manuscript. GP: next generation sequencing and sanger analysis, data collection, preparation of the manuscript. FN: enrolment of patients, data collection, preparation of the manuscript. PAB: enrolment of patients, data collection,preparation of the manuscript. NC: enrolment of patients, data collection,preparation of the manuscript. AA: enrolment of patients, data collection, preparation of the manuscript. EA: enrolment of patients, data collection, preparation of the manuscript. CT: dataset, data collection & analysis, preparation of the manuscript. LL: histological diagnosis, data collection, preparation of the manuscript. SA: histological diagnosis, data collection, preparation of the manuscript. LG: study concept, supervision of pathological analysis, preparation, and revision of the manuscript. ADN: study concept, supervision of pathological and molecular analysis, data collection & analysis, preparation and revision of the manuscript All the Authors read and approved the manuscript.

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Correspondence to M. Christina Cox or Arianna Di Napoli.

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Cox, M.C., Marcheselli, L., Scafetta, G. et al. IgM-secreting diffuse large B-cell lymphoma: results of a multicentre clinicopathological and molecular study. Leukemia 36, 2719–2723 (2022). https://doi.org/10.1038/s41375-022-01706-x

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