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Diagnostic value of bone marrow core biopsy patterns in lymphoplasmacytic lymphoma/Waldenström macroglobulinaemia and description of its mutational profiles by targeted NGS
  1. Julia Garcia-Reyero1,
  2. Nerea Martinez Magunacelaya1,
  3. Sonia Gonzalez de Villambrosia1,
  4. Angela Gomez Mediavilla1,
  5. Marcela Urquieta Lam1,
  6. Andres Insunza1,
  7. Raul Tonda2,
  8. Sergi Beltran2,
  9. Marta Gut2,
  10. Ainara Gonzalez1,
  11. Santiago Montes-Moreno1
  1. 1Anatomic Pathology Service, Hematology Service and Translational Hematopathology Lab, Hospital Universitario Marques de Valdecilla/IDIVAL. Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Santander, Cantabria, Spain
  2. 2Centre Nacional d’Anàlisi Genòmica (CNAG-CRG), Barcelona Institute of Science and Technology (BIST), Barcelona, Catalunya, Spain
  1. Correspondence to Dr Santiago Montes-Moreno, Anatomic Pathology Service and Translational Hematopathology Lab, Hospital Universitario Marques de Valdecilla/IDIVAL, Santander 39008, Spain; santiago.montes{at}


Aims The aim of this study was to describe the characteristics of the bone marrow infiltration found in a series of clinically defined lymphoplasmacytic lymphoma (LPL)/Waldenström macroglobulinaemia (WM) and IgM-monoclonal gammopathy of undetermined significance (MGUS) and to perform a targeted next-generation sequencing (NGS) for the identification of additional somatic mutations to MYD88p.L265P in LPL/WM.

Methods We have reviewed a series of 35 bone marrow biopsies from 28 patients with a clinical diagnosis of LPL/WM (24 cases) or MGUS (4 cases). Bone marrow infiltration characteristics by morphology, immunohistochemistry, flow cytometry (FCM), allele-specific real-time PCR for the detection of MYD88p.L265P mutation, targeted exonic amplicon-based NGS of 35 lymphoma-related genes and direct sequencing were analysed.

Results Our findings show that bone marrow trephine biopsy evaluation is superior to FCM in the identification of significant lymphoid infiltrates. A combined paratrabecular and interstitial infiltration pattern is the most common feature in LPL/WM while a patchy interstitial pattern characterises IgM-MGUS cases. MYD88p.L265P mutation was found by allele-specific-PCR in 92% of the LPL cases (22 out of 24) and 25% of IgM-MGUS cases (1 out of 4 cases). In addition to MYD88p.L265P somatic mutations in CXCR4, KMT2D, PRDM1/Blimp1, MYC and ID3 were found by NGS and direct sequencing in 4 cases.

Conclusions In conclusion, bone marrow core biopsy evaluation is critical in the identification of unequivocal bone marrow infiltration by LPL/WM. In addition to MYD88p.L265P, somatic mutations in CXCR4, KMT2D, PRDM1/Blimp1, MYC and ID3 can appear in a fraction of LPL/WM.

  • lymphoma
  • histopathology
  • molecular pathology

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  • Handling editor Mary Frances McMullin.

  • JG-R and NMM contributed equally.

  • Contributors JG-R, NMM, AGM, AG, RT, SB and MG performed research. SGdV, MUL ad AI provided clinical data. SM-M designed research, performed research and wrote the manuscript. All authors approved the manuscript.

  • Funding This study was supported by grants from MINECO (PI16/1397, SMM, Principal Investigator) and IDIVAL (NEXTVAL 15/09, SMM, Principal Investigator). NMM was supported by Asociación Española contra el Cancer (AECC).

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval The study and sample collection were approved by the local ethics committee (CEIC Cantabria) and complies with the Declaration of Helsinki. Informed written consent was obtained when required.

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

  • Data availability statement All data relevant to the study are included in the article or uploaded as supplementary information.