Skip to main content

Advertisement

SpringerLink
Log in

Transdifferentiation of mantle cell lymphoma into sarcoma with limited neuromuscular differentiation after conventional chemotherapy

  • Brief Report
  • Published:
Virchows Archiv Aims and scope Submit manuscript

Abstract

We report an exceptionally rare case of mantle cell lymphoma (MCL) that transdifferentiated into sarcoma with limited neuromuscular differentiation. An 81-year-old man with t(11;14)-positive MCL was treated with rituximab and bendamustine and achieved complete remission; however, just 2 months later, the patient developed multiple systemic tumors. Pathologic studies revealed round cell sarcoma expressing synaptophysin, CD56, and myogenin without any B-cell markers. The CCND1 translocation and an identical IGL gene rearrangement were shared by both the MCL and sarcoma. Whole-exome sequencing detected 189 single nucleotide variants (SNVs) in the MCL and 205 SNVs in the sarcoma; 160 SNVs including NSD2, ATM, RB1, and TP53 mutations were shared between MCL and sarcoma cells. An additional PTPN11 mutation was specifically found in the sarcoma. These findings confirmed the shared clonal origin of MCL and sarcoma in this patient and indicated that MCL can transdifferentiate into sarcoma in rare cases.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Availability of data and materials

The data and materials could be accessed via email to kirito@yamanashi.ac.jp.

Code availability

Not applicable.

References

  1. Feldman AL, Arber DA, Pittaluga S et al (2008) Clonally related follicular lymphomas and histiocytic/dendritic cell sarcomas: evidence for transdifferentiation of the follicular lymphoma clone. Blood 111:5433–5439. https://doi.org/10.1182/blood-2007-11-124792

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Ambrosio MR, De Falco G, Rocca BJ et al (2015) Langerhans cell sarcoma following marginal zone lymphoma: expanding the knowledge on mature B cell plasticity. Virchows Arch 467:471–480. https://doi.org/10.1007/s00428-015-1814-8

    Article  CAS  PubMed  Google Scholar 

  3. Shao H, Xi L, Raffeld M et al (2011) Clonally related histiocytic/dendritic cell sarcoma and chronic lymphocytic leukemia/small lymphocytic lymphoma: a study of seven cases. Mod Pathol 24:1421–1432. https://doi.org/10.1038/modpathol.2011.102

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Hure MC, Elco CP, Ward D et al (2012) Histiocytic Sarcoma arising from clonally related mantle cell lymphoma. J Clin Oncol 30:e49–e53. https://doi.org/10.1200/JCO.2011.38.8553

    Article  PubMed  Google Scholar 

  5. van Dongen JJM, Langerak AW, Brüggemann M et al (2003) Design and standardization of PCR primers and protocols for detection of clonal immunoglobulin and T-cell receptor gene recombinations in suspect lymphoproliferations: report of the BIOMED-2 Concerted Action BMH4-CT98-3936. Leukemia 17:2257–2317. https://doi.org/10.1038/sj.leu.2403202

    Article  PubMed  Google Scholar 

  6. Wang K, Li M, Hakonarson H (2010) ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data. Nucleic Acids Res 38:e164–e164. https://doi.org/10.1093/nar/gkq603

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Oliveros JC Venny. An interactive tool for comparing lists with Venn’s diagrams. https://bioinfogp.cnb.csic.es/tools/venny/index.html

  8. Sondka Z, Bamford S, Cole CG et al (2018) The COSMIC cancer gene census: describing genetic dysfunction across all human cancers. Nat Rev Cancer 1 https://doi.org/10.1038/s41568-018-0060-1

  9. Hill HA, Qi X, Jain P et al (2020) Genetic mutations and features of mantle cell lymphoma: a systematic review and meta-analysis. Blood Adv 4:2927–2938. https://doi.org/10.1182/bloodadvances.2019001350

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Beà S, Valdés-Mas R, Navarro A et al (2013) Landscape of somatic mutations and clonal evolution in mantle cell lymphoma. Proc Natl Acad Sci U S A 110:18250–18255. https://doi.org/10.1073/pnas.1314608110

    Article  PubMed  PubMed Central  Google Scholar 

  11. Ezquieta B, Santomé JL, Carcavilla A et al (2012) Alteraciones de los genes de la vía RAS-MAPK en 200 pacientes españoles con síndrome de Noonan y otros síndromes neurocardiofaciocutáneos. Genotipo y cardiopatía Rev Española Cardiol 65:447–455. https://doi.org/10.1016/j.recesp.2011.12.016

    Article  Google Scholar 

  12. Binder G, Grathwol S, von Loeper K et al (2012) Health and quality of life in adults with Noonan syndrome. J Pediatr 161:501-505.e1. https://doi.org/10.1016/j.jpeds.2012.02.043

    Article  PubMed  Google Scholar 

  13. Pannone L, Bocchinfuso G, Flex E et al (2017) Structural, Functional, and clinical characterization of a novel PTPN11 mutation cluster underlying Noonan syndrome. Hum Mutat 38:451–459. https://doi.org/10.1002/humu.23175

    Article  CAS  PubMed  Google Scholar 

  14. Zhang Q, Orlando EJ, Wang HY et al (2020) Transdifferentiation of lymphoma into sarcoma associated with profound reprogramming of the epigenome. Blood 136:1980–1983. https://doi.org/10.1182/blood.2020005123

    Article  PubMed  PubMed Central  Google Scholar 

  15. Jongmans MCJ, van der Burgt I, Hoogerbrugge PM et al (2011) Cancer risk in patients with Noonan syndrome carrying a PTPN11 mutation. Eur J Hum Genet 19:870–874. https://doi.org/10.1038/ejhg.2011.37

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Funding

This work was supported by JSPS KAKENHI Grant Number 19K16554.

Author information

Author notes

  1. Ichiro Kawashima and Naoki Oishi contributed equally to this work.

Authors and Affiliations

  1. Department of Hematology and Oncology, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi, 409-3898, Japan

    Ichiro Kawashima, Eriko Hosokawa, Ayato Nakadate, Minori Matsuura, Takuma Kumagai, Megumi Koshiishi, Takeo Yamamoto, Kei Nakajima, Masaru Tanaka & Keita Kirito

  2. Department of Pathology, University of Yamanashi, Chuo, Yamanashi, Japan

    Naoki Oishi, Kazunari Kasai, Tomohiro Inoue & Tetsuo Kondo

Authors
  1. Ichiro Kawashima
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Naoki Oishi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kazunari Kasai
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Tomohiro Inoue
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Eriko Hosokawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ayato Nakadate
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Minori Matsuura
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Takuma Kumagai
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Megumi Koshiishi
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Takeo Yamamoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Kei Nakajima
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Masaru Tanaka
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Tetsuo Kondo
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Keita Kirito
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

I.K., N.O., and K. Kirito collected data, constructed the figures, and wrote the manuscript; N.O., K. Kasai, T.I., and T. Kondo reviewed the histopathology; E.H, A.N., M.M., T. Kumagai, M.K., T. Y, K.N., and M.T. treated the patient and collected data, and all authors reviewed and edited the manuscript. IK and NO contributed equally to this work.

Corresponding author

Correspondence to Keita Kirito.

Ethics declarations

Ethics approval

This study is a case report, and the institute waved ethics approval.

Consent to participate

Consent to participate was acquired.

Consent for publication

Consent for publication was acquired.

Conflict of interest

The authors declare no competing interests.

Additional information

Publisher's note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kawashima, I., Oishi, N., Kasai, K. et al. Transdifferentiation of mantle cell lymphoma into sarcoma with limited neuromuscular differentiation after conventional chemotherapy. Virchows Arch 480, 1101–1105 (2022). https://doi.org/10.1007/s00428-021-03148-9

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00428-021-03148-9

Keywords

Search

Navigation