Skip to main content
SpringerLink
Log in

Identification of CD5/SOX11 double-negative pleomorphic mantle cell lymphoma

  • Original Article
  • Published:
Virchows Archiv Aims and scope Submit manuscript

Abstract

Cyclin D1 protein-positive diffuse large B cell lymphoma (DLBCL) has an immunophenotype of CD5(−) cyclin D1(+) SOX11(−), and most cases lack a CCND1 rearrangement and have a gene expression profile of DLBCL. Rarely, cyclin D1 protein-positive DLBCL harbors a CCND1 rearrangement, and some genetic copy number features typical of mantle cell lymphoma (MCL) have been detected. Since gene expression studies have not been performed, whether such CCND1-rearranged cases represent cyclin D1 protein-positive DLBCL or CD5/SOX11 double-negative pleomorphic MCL remains unclear. To date, no cases of CD5/SOX11 double-negative MCL have been reported. In this study, we collected eight cases initially diagnosed as cyclin D1 protein-positive DLBCL, including four with a CCND1 rearrangement and four without. Immunohistochemically, all four CCND1-rearranged cases had >50% of tumor cells positive for cyclin D1 protein, whereas only one (25%) non-rearranged case had >50% positive tumor cells. Analysis of genome-wide copy number, mutational, and gene expression profiles revealed that CCND1-rearranged cases were similar to MCL, whereas CCND1-non-rearranged cases resembled DLBCL. Despite the SOX11 negativity by immunohistochemistry, CCND1-rearranged cases had a notable trend (P = 0.064) of higher SOX11 mRNA levels compared to non-rearranged cases. Here, we show for the first time that CCND1 rearrangement could be useful for identifying CD5/SOX11 double-negative pleomorphic MCL in cases diagnosed as cyclin D1 protein-positive DLBCL. Cases with >50% cyclin D1 protein-positive tumor cells immunohistochemically and higher SOX11 mRNA levels are more likely to have a CCND1 rearrangement, and fluorescence in situ hybridization can be used to detect the rearrangement.

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
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Swerdlow SH, Campo E, Seto M et al (2017) Mantle cell lymphoma. In: Swerdlow SH, Campo E, Harris NL et al (eds) WHO Classification of the Tumours of Haematopoietic and Lymphoid Tissues, revised, 4th edn. IARC, Lyon, pp 285–290

    Google Scholar 

  2. Dreyling M, Klapper W, Rule S (2018) Blastoid and pleomorphic mantle cell lymphoma: still a diagnostic and therapeutic challenge! Blood 132:2722–2729

    Article  CAS  PubMed  Google Scholar 

  3. Miao Y, Lin P, Saksena A et al (2019) CD5-negative mantle cell lymphoma: clinicopathologic correlations and outcome in 58 patients. Am J Surg Pathol 43:1052–1060

    Article  PubMed  Google Scholar 

  4. Zeng W, Fu K, Quintanilla-Fend L et al (2012) Cyclin D1-negative blastoid mantle cell lymphoma identified by SOX11 expression. Am J Surg Pathol 36:214–219

    Article  PubMed  Google Scholar 

  5. Chuang WY, Chang H, Chang GJ et al (2017) Pleomorphic mantle cell lymphoma morphologically mimicking diffuse large B cell lymphoma: common cyclin D1 negativity and a simple immunohistochemical algorithm to avoid the diagnostic pitfall. Histopathology 70:986–999

    Article  PubMed  Google Scholar 

  6. Xu J, Wang L, Li J et al (2019) SOX11-negative mantle cell lymphoma: clinicopathologic and prognostic features of 75 patients. Am J Surg Pathol 43:710–716

    Article  PubMed  Google Scholar 

  7. Chuang WY, Chang ST, Yuan CT et al (2020) Identification of CD5/cyclin D1 double-negative pleomorphic mantle cell lymphoma: a clinicopathologic, genetic, and gene expression study. Am J Surg Pathol 44:232–240

    Article  PubMed  Google Scholar 

  8. Ok CY, Xu-Monette ZY, Tzankov A et al (2014) Prevalence and clinical implications of cyclin D1 expression in diffuse large B-cell lymphoma (DLBCL) treated with immunochemotherapy: a report from the International DLBCL Rituximab-CHOP Consortium Program. Cancer 120:1818–1829

    Article  CAS  PubMed  Google Scholar 

  9. Hsiao SC, Cortada IR, Colomo L et al (2012) SOX11 is useful in differentiating cyclin D1-positive diffuse large B-cell lymphoma from mantle cell lymphoma. Histopathology 61:685–693

    Article  PubMed  Google Scholar 

  10. Juskevicius D, Ruiz C, Dirnhofer S et al (2014) Clinical, morphologic, phenotypic, and genetic evidence of cyclin D1-positive diffuse large B-cell lymphomas with CYCLIN D1 gene rearrangements. Am J Surg Pathol 38:719–727

    Article  PubMed  Google Scholar 

  11. Al-Kawaaz M, Mathew S, Liu Y et al (2015) Cyclin D1-positive diffuse large B-cell lymphoma with IGH-CCND1 translocation and BCL6 rearrangement: a report of two cases. Am J Clin Pathol 143:288–299

    Article  CAS  PubMed  Google Scholar 

  12. Gao D, Liu Z (2019) Cyclin D1 + large B-cell lymphoma with altered CCND1 and BCL-6 rearrangements: a diagnostic challenge. Biomark Res 7:11

    Article  PubMed  PubMed Central  Google Scholar 

  13. Parrott AM, Haggiagi AM, Murty VV et al (2020) Primary large B-cell lymphoma of the central nervous system with cyclin D1 expression and t(11;14) (IGH-CCND1): diffuse large B-cell lymphoma with CCND1 rearrangement or mantle cell lymphoma? Hematol Oncol 38:817–822

    Article  CAS  PubMed  Google Scholar 

  14. Cheng J, Hashem MA, Barabé F et al (2021) CCND1 genomic rearrangement as a secondary event in high grade B-cell lymphoma. Hemasphere 5:e505

    Article  PubMed  Google Scholar 

  15. Cheson BD, Fisher RI, Barrington SF et al (2014) Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol 32:3059–3068

    Article  PubMed  PubMed Central  Google Scholar 

  16. Hans CP, Weisenburger DD, Greiner TC et al (2004) Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray. Blood 103:275–282

    Article  CAS  PubMed  Google Scholar 

  17. Johnson NA, Slack GW, Savage KJ et al (2012) Concurrent expression of MYC and BCL2 in diffuse large B-cell lymphoma treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone. J Clin Oncol 30:3452–3459

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Chuang WY, Chang H, Shih LY et al (2015) CD5 positivity is an independent adverse prognostic factor in elderly patients with diffuse large B cell lymphoma. Virchows Arch 467:571–582

    Article  CAS  PubMed  Google Scholar 

  19. Fu K, Weisenburger DD, Greiner TC et al (2005) Cyclin D1-negative mantle cell lymphoma: a clinicopathologic study based on gene expression profiling. Blood 106:4315–4321

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Scott DW, Wright GW, Williams PM et al (2014) Determining cell-of-origin subtypes of diffuse large B-cell lymphoma using gene expression in formalin-fixed paraffin-embedded tissue. Blood 123:1214–1217

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Babicki S, Arndt D, Marcu A et al (2016) Heatmapper: web-enabled heat mapping for all. Nucleic Acids Res 44:W147–W153

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Grau M, López C, Martín-Subero JI et al (2023) Cytogenomics of B-cell non-Hodgkin lymphomas: The “old” meets the “new.”. Best Pract Res Clin Haematol 36:101513

    Article  CAS  PubMed  Google Scholar 

  23. 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Gascoyne RD, Campo E, Jaffe ES et al (2017) Diffuse large B-cell lymphoma, NOS. In: Swerdlow SH, Campo E, Harris NL et al (eds) WHO Classification of the Tumours of Haematopoietic and Lymphoid Tissues, revised, 4th edn. IARC, Lyon, pp 291–297

    Google Scholar 

  25. Wright GW, Huang DW, Phelan JD et al (2020) A probabilistic classification tool for genetic subtypes of diffuse large B cell lymphoma with therapeutic implications. Cancer Cell 37:551–568

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Miyazaki K, Yamaguchi M, Imai H et al (2015) Gene expression profiling of diffuse large B-Cell lymphomas supervised by CD5 expression. Int J Hematol 102:188–194

    Article  CAS  PubMed  Google Scholar 

  27. Vela-Chávez T, Adam P, Kremer M et al (2011) Cyclin D1 positive diffuse large B-cell lymphoma is a post-germinal center-type lymphoma without alterations in the CCND1 gene locus. Leuk Lymphoma 52:458–466

    Article  PubMed  PubMed Central  Google Scholar 

  28. Jain P, Zhang S, Kanagal-Shamanna R et al (2020) Genomic profiles and clinical outcomes of de novo blastoid/pleomorphic MCL are distinct from those of transformed MCL. Blood Adv 4:1038–1050

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Li S, Tang G, Jain P et al (2024) Cyclin D1-negative blastoid/pleomorphic mantle cell lymphoma or large B-cell lymphoma? Mod Pathol 37:100405

    Article  PubMed  Google Scholar 

  30. Balsas P, Palomero J, Eguileor Á et al (2017) SOX11 promotes tumor protective microenvironment interactions through CXCR4 and FAK regulation in mantle cell lymphoma. Blood 130:501–513

    Article  CAS  PubMed  Google Scholar 

  31. Navarro A, Clot G, Royo C et al (2012) Molecular subsets of mantle cell lymphoma defined by the IGHV mutational status and SOX11 expression have distinct biologic and clinical features. Cancer Res 72:5307–5316

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Royo C, Navarro A, Clot G et al (2012) Non-nodal type of mantle cell lymphoma is a specific biological and clinical subgroup of the disease. Leukemia 26:1895–1898

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Foucar K, Falini B, Stein H (2017) Hairy cell leukemia. In: Swerdlow SH, Campo E, Harris NL et al (eds) WHO Classification of the Tumours of Haematopoietic and Lymphoid Tissues, revised, 4th edn. IARC, Lyon, pp 226–228

    Google Scholar 

  34. McKenna RW, Kyle RA, Kuehl WM et al (2017) Plasma cell neoplasms. In: Swerdlow SH, Campo E, Harris NL et al (eds) WHO Classification of the Tumours of Haematopoietic and Lymphoid Tissues, revised, 4th edn. IARC, Lyon, pp 241–258

    Google Scholar 

  35. Chen D, Ketterling RP, Hanson CA et al (2011) A case of hairy cell leukemia with CCND1-IGH@ translocation: indolent non-nodal mantle cell lymphoma revisited. Am J Surg Pathol 35:1080–1084

    Article  PubMed  Google Scholar 

Download references

Funding

This study was supported by the National Science and Technology Council, Taiwan (NSTC112-2320-B-182-054), the Chang Gung Medical Foundation (CMRPG3M2051), and the Johnson & Johnson Taiwan Ltd. (T19016).

Author information

Authors and Affiliations

  1. Department of Pathology, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan

    Wen-Yu Chuang, Chi-Ju Yeh, Shir-Hwa Ueng & Chuen Hsueh

  2. School of Medicine, Chang Gung University, Taoyuan, Taiwan

    Wen-Yu Chuang, Hung Chang, Lee-Yung Shih, Chi-Ju Yeh, Shir-Hwa Ueng, Ming-Chung Kuo, Hsiao-Wen Kao & Chuen Hsueh

  3. Chang Gung Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan

    Wen-Yu Chuang, Shir-Hwa Ueng, Hsuan Liu, Jau-Song Yu & Chuen Hsueh

  4. Center for Vascularized Composite Allotransplantation, Chang Gung Memorial Hospital, Taoyuan, Taiwan

    Wen-Yu Chuang

  5. Division of Hematology and Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan

    Hung Chang, Lee-Yung Shih, Ming-Chung Kuo & Hsiao-Wen Kao

  6. Genomic Medicine Core Laboratory, Department of Medical Research and Development, Chang Gung Memorial Hospital, Taoyuan, Taiwan

    Tsung-Chieh Lin

  7. Department of Biomedical Sciences, Chang Gung University, Taoyuan, Taiwan

    Tsung-Chieh Lin

  8. Department of Pathology, Chi-Mei Medical Center, Tainan, Taiwan

    Sheng-Tsung Chang & Shih-Sung Chuang

  9. Department of Pathology, Taichung Tzu Chi Hospital, Taichung, Taiwan

    Chih-Ling Lee

  10. Department of Hematology and Oncology, Taichung Tzu Chi Hospital, Taichung, Taiwan

    Kuan-Po Huang

  11. Tissue Bank, Chang Gung Memorial Hospital, Taoyuan, Taiwan

    Tong-Hong Wang

  12. Department of Medical Imaging and Intervention, Chang Gung Memorial Hospital, Taoyuan, Taiwan

    Yung-Liang Wan

Authors
  1. Wen-Yu Chuang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hung Chang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lee-Yung Shih
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Tsung-Chieh Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Chi-Ju Yeh
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Shir-Hwa Ueng
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ming-Chung Kuo
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Hsiao-Wen Kao
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Hsuan Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Sheng-Tsung Chang
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Chih-Ling Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Kuan-Po Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Tong-Hong Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Yung-Liang Wan
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Jau-Song Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Chuen Hsueh
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Shih-Sung Chuang
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

The conception of the study was designed by WYC and SSC. Material preparation was performed by WYC, TCL, CJY, SHU, HL, STC, CLL, THW, JSY, CH, and SSC. Data collection was performed by WYC, HC, LYS, MCK, HWK, KPH, YLW, and SSC. The data were analyzed by WYC, TCL, HL, JSY, and SSC. The first draft of the manuscript was written by WYC, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Shih-Sung Chuang.

Ethics declarations

Ethics approval

This study was approved by the Institutional Review Boards of Chang Gung Medical Foundation (201902130B0, 202000483B0, 202201498B0, and 202202021B0) and Chi-Mei Medical Center (10604-003).

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.

Supplementary information

ESM 1

(PDF 143 kb)

ESM 2

(PDF 112 kb)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chuang, WY., Chang, H., Shih, LY. et al. Identification of CD5/SOX11 double-negative pleomorphic mantle cell lymphoma. Virchows Arch (2024). https://doi.org/10.1007/s00428-024-03813-9

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s00428-024-03813-9

Keywords

Search

Navigation