Skip to main content

Advertisement

Log in

Nodal EBV-positive polymorphic B cell lymphoproliferative disorder with plasma cell differentiation: clinicopathological analysis of five cases

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

Abstract

Plasma cell differentiation (PCD) is frequently observed in some entities of non-Hodgkin B cell lymphoma, including both low-grade and high-grade lymphomas. However, except for plasmablastic lymphoma and primary effusion lymphoma, EBV+ B cell lymphoproliferative disorder (LPD) with PCD has not been well addressed due to its rarity. We clinicopathologically examined five cases of nodal EBV+ polymorphic B cell LPD with PCD (PBLPD-PCD) initially diagnosed as polymorphic EBV+ diffuse large B cell lymphoma, not otherwise specified (DLBCL-NOS) with PCD (n = 3) and methotrexate-associated B cell LPD (MTX-associated B-LPD) (n = 2). One case had a concomitant brain lesion which was clinically diagnosed as EBV-related encephalitis. This patient received therapy with vidarabine, and both the brain lesion and the nodal EBV+ PBLPD-PCD lesions disappeared. Another case was characterized by Mott cell differentiation. This case was the first reported case of EBV+ B cell lymphoma or LPD with Mott cell differentiation. The two cases of MTX-associated B cell LPD which arose in patients with rheumatoid arthritis spontaneously regressed after MTX cessation. TCRγ and IGH PCR analysis was performed in four cases. Two cases had TCRγ rearrangements, but no IGH rearrangements. The other two cases had no rearrangements in these genes. We concluded that nodal EBV+ PBLPD-PCD is rare, with heterogeneous characteristics. PCR analysis revealed that nodal EBV+ PBLPD-PCD may have only TCR clonality and no IGH clonality. Considering the partial or complete loss of CD20 expression on the tumor cells, this result may be confusing for accurate diagnosis of EBV+ PBLPD-PCD, and pathologists need to be aware of this phenomenon to avoid misdiagnosis.

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

Access this article

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

Similar content being viewed by others

References

  1. Swerdlow S, Campo E, Harris N, Jaffe E, Pileri S, Stein H, Thiele J (eds) (2017) WHO classification of tumours of haematopoietic and lymphoid tissues. World Health Organization Classification of Tumours, Revised, 4th edn. International Agency for Research on Cancer, Lyon

    Google Scholar 

  2. Oyama T, Ichimura K, Suzuki R, Suzumiya J, Ohshima K, Yatabe Y, Yokoi T, Kojima M, Kamiya Y, Taji H, Kagami Y, Ogura M, Saito H, Morishima Y, Nakamura S (2003) Senile EBV+ B-cell lymphoproliferative disorders: a clinicopathologic study of 22 patients. Am J Surg Pathol 27(1):16–26. https://doi.org/10.1097/00000478-200301000-00003

    Article  PubMed  Google Scholar 

  3. Hoshida Y, Xu JX, Fujita S, Nakamichi I, Ikeda J, Tomita Y, Nakatsuka S, Tamaru J, Iizuka A, Takeuchi T, Aozasa K (2007) Lymphoproliferative disorders in rheumatoid arthritis: clinicopathological analysis of 76 cases in relation to methotrexate medication. J Rheumatol 34(2):322–331

    CAS  PubMed  Google Scholar 

  4. Ichikawa A, Arakawa F, Kiyasu J, Sato K, Miyoshi H, Niino D, Kimura Y, Takeuchi M, Yoshida M, Ishibashi Y, Nakashima S, Sugita Y, Miura O, Ohshima K (2013) Methotrexate/iatrogenic lymphoproliferative disorders in rheumatoid arthritis: histology, Epstein-Barr virus, and clonality are important predictors of disease progression and regression. Eur J Haematol 91(1):20–28. https://doi.org/10.1111/ejh.12116

    Article  CAS  PubMed  Google Scholar 

  5. Kurita D, Miyoshi H, Ichikawa A, Kato K, Imaizumi Y, Seki R, Sato K, Sasaki Y, Kawamoto K, Shimono J, Yamada K, Muto R, Kizaki M, Nagafuji K, Tamaru JI, Tokuhira M, Ohshima K (2019) Methotrexate-associated lymphoproliferative disorders in patients with rheumatoid arthritis: clinicopathologic features and prognostic factors. Am J Surg Pathol 43(7):869–884. https://doi.org/10.1097/pas.0000000000001271

    Article  PubMed  Google Scholar 

  6. Satou A, Banno S, Hanamura I, Takahashi E, Takahara T, Nobata H, Katsuno T, Takami A, Ito Y, Ueda R, Nakamura S, Tsuzuki T (2019) EBV-positive mucocutaneous ulcer arising in rheumatoid arthritis patients treated with methotrexate: single center series of nine cases. Pathol Int 69:21–28. https://doi.org/10.1111/pin.12745

    Article  CAS  PubMed  Google Scholar 

  7. Satou A, Tabata T, Miyoshi H, Kohno K, Suzuki Y, Yamashita D, Shimada K, Kawasaki T, Sato Y, Yoshino T, Ohshima K, Takahara T, Tsuzuki T, Nakamura S (2019) Methotrexate-associated lymphoproliferative disorders of T-cell phenotype: clinicopathological analysis of 28 cases. Mod Pathol 32(8):1135–1146. https://doi.org/10.1038/s41379-019-0264-2

    Article  CAS  PubMed  Google Scholar 

  8. Harmon CM, Smith LB (2016) B-cell non-Hodgkin lymphomas with plasmacytic differentiation. Surg Pathol Clin 9(1):11–28. https://doi.org/10.1016/j.path.2015.09.007

    Article  PubMed  Google Scholar 

  9. Castillo JJ, Bibas M, Miranda RN (2015) The biology and treatment of plasmablastic lymphoma. Blood 125(15):2323–2330. https://doi.org/10.1182/blood-2014-10-567479

    Article  CAS  PubMed  Google Scholar 

  10. Shimada K, Hayakawa F, Kiyoi H (2018) Biology and management of primary effusion lymphoma. Blood 132(18):1879–1888. https://doi.org/10.1182/blood-2018-03-791426

    Article  CAS  PubMed  Google Scholar 

  11. Nakatsuka SI, Yutani C, Kurashige M, Kohara M, Nagano T, Goto T, Takatsuka H, Ifuku H, Morii E (2017) An unusual case of Epstein-Barr virus-positive large B-cell lymphoma lacking various B-cell markers. Diag Pathol 12(1):15. https://doi.org/10.1186/s13000-017-0606-7

    Article  Google Scholar 

  12. Starr A, Kwon DH, Kallakury B (2019) Epstein-Barr virus-positive CD20- and CD45-negative diffuse large B-cell lymphoma: a diagnostic challenge. Int J Surg Pathol 27(1):98–101. https://doi.org/10.1177/1066896918784669

    Article  PubMed  Google Scholar 

  13. Hsiao SC, Ichinohasama R, Lin SH, Liao YL, Chang ST, Cho CY, Chuang SS (2009) EBV-associated diffuse large B-cell lymphoma in a psoriatic treated with methotrexate. Pathol Res Pract 205(1):43–49. https://doi.org/10.1016/j.prp.2008.08.006

    Article  PubMed  Google Scholar 

  14. McKelvie P, Yixing Lai F, Verma A, Bazargan A (2016) Methotrexate-associated EBV-positive CD20-negative diffuse large B-cell lymphoma localized to skin presenting as multiple chronic lower leg ulcers. Leuk Lymphoma 57(2):456–460. https://doi.org/10.3109/10428194.2015.1049165

    Article  PubMed  Google Scholar 

  15. Asano N, Suzuki R, Kagami Y, Ishida F, Kitamura K, Fukutani H, Morishima Y, Takeuchi K, Nakamura S (2005) Clinicopathologic and prognostic significance of cytotoxic molecule expression in nodal peripheral T-cell lymphoma, unspecified. Am J Surg Pathol 29(10):1284–1293. https://doi.org/10.1097/01.pas.0000173238.17331.6b

    Article  PubMed  Google Scholar 

  16. van Dongen JJ, Langerak AW, Bruggemann M, Evans PA, Hummel M, Lavender FL, Delabesse E, Davi F, Schuuring E, Garcia-Sanz R, van Krieken JH, Droese J, Gonzalez D, Bastard C, White HE, Spaargaren M, Gonzalez M, Parreira A, Smith JL, Morgan GJ, Kneba M, Macintyre EA (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(12):2257–2317. https://doi.org/10.1038/sj.leu.2403202

    Article  PubMed  Google Scholar 

  17. Satou A, Asano N, Nakazawa A, Osumi T, Tsurusawa M, Ishiguro A, Elsayed AA, Nakamura N, Ohshima K, Kinoshita T, Nakamura S (2015) Epstein-Barr virus (EBV)-positive sporadic burkitt lymphoma: an age-related lymphoproliferative disorder? Am J Surg Pathol 39(2):227–235. https://doi.org/10.1097/pas.0000000000000332

    Article  PubMed  Google Scholar 

  18. Ventura RA, Martin-Subero JI, Jones M, McParland J, Gesk S, Mason DY, Siebert R (2006) FISH analysis for the detection of lymphoma-associated chromosomal abnormalities in routine paraffin-embedded tissue. J Mol Diag: JMD 8(2):141–151. https://doi.org/10.2353/jmoldx.2006.050083

    Article  CAS  Google Scholar 

  19. Liu F, Asano N, Tatematsu A, Oyama T, Kitamura K, Suzuki K, Yamamoto K, Sakamoto N, Taniwaki M, Kinoshita T, Nakamura S (2012) Plasmablastic lymphoma of the elderly: a clinicopathological comparison with age-related Epstein-Barr virus-associated B cell lymphoproliferative disorder. Histopathology 61(6):1183–1197. https://doi.org/10.1111/j.1365-2559.2012.04339.x

    Article  PubMed  Google Scholar 

  20. Valera A, Balagué O, Colomo L, Martínez A, Delabie J, Taddesse-Heath L, Jaffe ES, Campo E (2010) IG/MYC rearrangements are the main cytogenetic alteration in plasmablastic lymphomas. Am J Surg Pathol 34(11):1686–1694. https://doi.org/10.1097/PAS.0b013e3181f3e29f

    Article  PubMed  PubMed Central  Google Scholar 

  21. Chadburn A, Said J, Gratzinger D, Chan JK, de Jong D, Jaffe ES, Natkunam Y, Goodlad JR (2017) HHV8/KSHV-positive lymphoproliferative disorders and the spectrum of plasmablastic and plasma cell neoplasms: 2015 SH/EAHP Workshop Report-part 3. Am J Clin Pathol 147(2):171–187. https://doi.org/10.1093/ajcp/aqw218

    Article  PubMed  PubMed Central  Google Scholar 

  22. Joo M (2015) Gastric mucosa-associated lymphoid tissue lymphoma masquerading as Russell body gastritis. Pathol Int 65(7):396–398. https://doi.org/10.1111/pin.12281

    Article  PubMed  Google Scholar 

  23. Zhang H, Jin Z, Cui R (2014) Russell body gastritis/duodenitis: a case series and description of immunoglobulin light chain restriction. Clin Res Hepatol Gastroenterol 38(5):e89–e97. https://doi.org/10.1016/j.clinre.2014.05.008

    Article  PubMed  Google Scholar 

  24. Kai K, Miyahara M, Tokuda Y, Kido S, Masuda M, Takase Y, Tokunaga O (2013) A case of mucosa-associated lymphoid tissue lymphoma of the gastrointestinal tract showing extensive plasma cell differentiation with prominent Russell bodies. World J Clin Cases 1(5):176–180. https://doi.org/10.12998/wjcc.v1.i5.176

    Article  PubMed  PubMed Central  Google Scholar 

  25. Chong Y, Kang CS, Oh WJ, Kim TJ, Lee EJ (2014) Nodal involvement of extranodal marginal zone lymphoma with extreme plasmacytic differentiation (Mott cell formation) simulating plasma cell neoplasm and lymphoplasmacytic lymphoma. Blood Res 49(4):275–285. https://doi.org/10.5045/br.2014.49.4.275

    Article  PubMed  PubMed Central  Google Scholar 

  26. Tanimoto A, Hamada T, Yamamoto T, Kimura S, Matsuki Y, Sasaguri Y (2002) MALT lymphoma with extreme plasma cell differentiation of the rectum. Am J Gastroenterol 97(7):1860–1862. https://doi.org/10.1111/j.1572-0241.2002.05879.x

    Article  PubMed  Google Scholar 

  27. Shintaku M, Asagoe K (2020) Follicular lymphoma with prominent Mott cell formation. Pathol Int 70:231–233. https://doi.org/10.1111/pin.12907

    Article  PubMed  Google Scholar 

  28. Saburi Y, Otsuka E, Urabe S, Satou A (2016) Follicular lymphoma associated with marked proliferation of Mott cells. Int J Hematol 104(6):639–640. https://doi.org/10.1007/s12185-016-2107-y

    Article  PubMed  Google Scholar 

  29. Dojcinov SD, Venkataraman G, Raffeld M, Pittaluga S, Jaffe ES (2010) EBV positive mucocutaneous ulcer--a study of 26 cases associated with various sources of immunosuppression. Am J Surg Pathol 34(3):405–417. https://doi.org/10.1097/PAS.0b013e3181cf8622

    Article  PubMed  PubMed Central  Google Scholar 

  30. Au WY, Ma ES, Choy C, Chung LP, Fung TK, Liang R, Kwong YL (2006) Therapy-related lymphomas in patients with autoimmune diseases after treatment with disease-modifying anti-rheumatic drugs. Am J Hematol 81(1):5–11. https://doi.org/10.1002/ajh.20508

    Article  CAS  PubMed  Google Scholar 

  31. Callan MF, Steven N, Krausa P, Wilson JD, Moss PA, Gillespie GM, Bell JI, Rickinson AB, McMichael AJ (1996) Large clonal expansions of CD8+ T cells in acute infectious mononucleosis. Nat Med 2(8):906–911. https://doi.org/10.1038/nm0896-906

    Article  CAS  PubMed  Google Scholar 

  32. Masucci MG, Ernberg I (1994) Epstein-Barr virus: adaptation to a life within the immune system. Trends Microbiol 2(4):125–130. https://doi.org/10.1016/0966-842x(94)90599-1

    Article  CAS  PubMed  Google Scholar 

  33. Sakakibara A, Kohno K, Eladl AE, Klaisuwan T, Ishikawa E, Suzuki Y, Shimada S, Nakaguro M, Shimoyama Y, Takahara T, Kato S, Asano N, Nakamura S, Satou A (2018) Immunohistochemical assessment of the diagnostic utility of PD-L1: a preliminary analysis of anti-PD-L1 antibody (SP142) for lymphoproliferative diseases with tumour and non-malignant Hodgkin-Reed-Sternberg (HRS)-like cells. Histopathology 72(7):1156–1163. https://doi.org/10.1111/his.13475

    Article  PubMed  Google Scholar 

  34. Kiyasu J, Miyoshi H, Hirata A, Arakawa F, Ichikawa A, Niino D, Sugita Y, Yufu Y, Choi I, Abe Y, Uike N, Nagafuji K, Okamura T, Akashi K, Takayanagi R, Shiratsuchi M, Ohshima K (2015) Expression of programmed cell death ligand 1 is associated with poor overall survival in patients with diffuse large B-cell lymphoma. Blood 126(19):2193–2201. https://doi.org/10.1182/blood-2015-02-629600

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Nicolae A, Pittaluga S, Abdullah S, Steinberg SM, Pham TA, Davies-Hill T, Xi L, Raffeld M, Jaffe ES (2015) EBV-positive large B-cell lymphomas in young patients: a nodal lymphoma with evidence for a tolerogenic immune environment. Blood 126(7):863–872. https://doi.org/10.1182/blood-2015-02-630632

  36. Lloyd IE, Clement PW, Salzman KL, Jensen RL, Salama ME, Palmer CA (2015) An unusual and challenging case of HIV-associated primary CNS lymphoma with Hodgkin-like morphology and HIV encephalitis. Diag Pathol 10:152. https://doi.org/10.1186/s13000-015-0387-9

    Article  CAS  Google Scholar 

  37. Nebuloni M, Vago L, Boldorini R, Bonetto S, Costanzi G (1998) VZV fulminant necrotizing encephalitis with concomitant EBV-related lymphoma and CMV ventriculitis: report of an AIDS case. J Neuro-Oncol 4(4):457–460. https://doi.org/10.3109/13550289809114546

    Article  CAS  Google Scholar 

  38. Noda Y, Ohtsuka Y, Yasui N, Sekiguchi K, Kawakami A, Nakamura S, Kanda F, Toda T (2011) A case of age-related Epstein-Barr virus-associated B-cell lymphoproliferative disorder which presented with encephalitis-like images. Rinsho Shinkeigaku 51(3):207–210. https://doi.org/10.5692/clinicalneurol.51.207

    Article  PubMed  Google Scholar 

  39. Copur MS, Deshpande A, Mleczko K, Norvell M, Hrnicek GJ, Woodward S, Frankforter S, Mandolfo N, Fu K, Chan WC (2005) Full clinical recovery after topical acyclovir treatment of Epstein-Barr virus associated cutaneous B-cell lymphoma in patient with mycosis fungoides. Croat Med J 46(3):458–462

    PubMed  Google Scholar 

Download references

Funding

This work was supported, in part, by grants from the Grants-in-Aid for Scientific Research (grant number: 18K15104).

Author information

Authors and Affiliations

Authors

Contributions

A.S.: proposed the study, reviewed the histopathology of all tumors, interpreted the result of the immunostaining, collected the data, and wrote the paper. T.T., Y.S., I.T., K.M., N.O., T.T., T.Y., and T.T.: collected the data and revised the manuscript. S.N.: reviewed the histopathology of all tumors, interpreted the result of the immunostaining, and revised the manuscript.

Corresponding author

Correspondence to Akira Satou.

Ethics declarations

The institutional review board of Aichi Medical University Hospital approved the study protocol.

Conflict of interest

The authors declare that they have no conflict of interest.

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

Satou, A., Tabata, T., Suzuki, Y. et al. Nodal EBV-positive polymorphic B cell lymphoproliferative disorder with plasma cell differentiation: clinicopathological analysis of five cases. Virchows Arch 478, 969–976 (2021). https://doi.org/10.1007/s00428-020-02967-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00428-020-02967-6

Keywords

Navigation