Abstract
Primary central nervous system lymphoma (PCNSL) sometimes occurs in immune-compromised hosts or patients with autoimmune diseases. Some cohort studies have previously reported an increased risk of non-Hodgkin’s lymphoma in systemic lupus erythematosus (SLE), while some cases of PCNSL in patients with SLE were reported. We present the case of PCNSL which developed in a patient with the active phase of neuropsychiatric SLE (NPSLE). Furthermore, we reviewed published English articles to confirm the characteristics of PCNSL related to SLE. To our knowledge, this is the first report of PCNSL occurring in NPSLE. Histology demonstrated B-cell lymphoma with a positive Epstein–Barr virus-encoded RNA. This patient recovered following surgical resection of the lymphoma, whole brain radiation therapy, intravenous infusion of rituximab (RTX), and administration of belimumab after RTX. Given the series of reviews, our report suggests that the persistence of damage in the central nervous system (CNS) and long-term exposure to immunosuppressants may impact oncogenic immune responses within the CNS, leading to PCNSL development.
Similar content being viewed by others
References
Bernatsky S, Ramsey-Goldman R, Labrecque J, Joseph L, Boivin JF, Petri M et al (2013) Cancer risk in systemic lupus: an updated international multi-centre cohort study. J Autoimmun 42:130–135. https://doi.org/10.1016/j.jaut.2012.12.009
Cao L, Tong H, Xu G, Liu P, Meng H, Wang J et al (2015) Systemic lupus erythematous and malignancy risk: a meta-analysis. PLoS ONE 10:e0122964. https://doi.org/10.1371/journal.pone.0122964
Zintzaras E, Voulgarelis M, Moutsopoulos HM (2005) The risk of lymphoma development in autoimmune diseases: a meta-analysis. Arch Intern Med 165:2337–2344. https://doi.org/10.1001/archinte.165.20.2337
Bernatsky S, Ramsey-Goldman R, Joseph L, Boivin JF, Costenbader KH, Urowitz MB et al (2014) Lymphoma risk in systemic lupus: effects of disease activity versus treatment. Ann Rheum Dis 73:138–142. https://doi.org/10.1136/annrheumdis-2012-202099
Han CH, Batchelor TT (2017) Diagnosis and management of primary central nervous system lymphoma. Cancer 123:4314–4324. https://doi.org/10.1002/cncr.30965
Deckert M, Brunn A, Montesinos-Rongen M, Terreni MR, Ponzoni M (2014) Primary lymphoma of the central nervous system—a diagnostic challenge. Hematol Oncol 32:57–67. https://doi.org/10.1002/hon.2087
Lipsmeyer EA (1972) Development of malignant cerebral lymphoma in a patient with systemic lupus erythematosus treated with immunosuppression. Arthritis Rheum 15:183–186. https://doi.org/10.1002/art.1780150207
Woolf AS, Conway G (1987) Systemic lupus erythematosus and primary cerebral lymphoma. Postgrad Med J 63:569–571. https://doi.org/10.1136/pgmj.63.741.569
Cras P, Franckx C, Martin JJ (1989) Primary intracerebral lymphoma in systemic lupus erythematosus treated with immunosuppressives. Clin Neuropathol 8:200–205.
Abdel Aziz KM, van Loveren HR (1999) Primary lymphoma of Meckel’s cave mimicking trigeminal schwannoma: case report. Neurosurgery 44:859–862. https://doi.org/10.1097/00006123-199904000-00096(discussion 862-853)
Dasgupta N, Gelber AC, Racke F, Fine DM (2005) Central nervous system lymphoma associated with mycophenolate mofetil in lupus nephritis. Lupus 14:910–913. https://doi.org/10.1191/0961203303lu2179cr
Finelli PF, Naik K, DiGiuseppe JA, Prasad A (2006) Primary lymphoma of CNS, mycophenolate mofetil and lupus. Lupus 15:886–888. https://doi.org/10.1177/0961203306071431
Steckley JL, Tartaglia MC, Reddy H, Huang S, Hammond R, Hyson C (2009) Systemic lupus erythematosus and right leg weakness. Can J Neurol Sci 36:98–101. https://doi.org/10.1017/s0317167100006405
Tsang HH, Trendell-Smith NJ, Wu AK, Mok MY (2010) Diffuse large B-cell lymphoma of the central nervous system in mycophenolate mofetil-treated patients with systemic lupus erythematosus. Lupus 19:330–333. https://doi.org/10.1177/0961203309347921
Biasiotta A, Frati A, Salvati M, Raco A, Fazi M, D’Elia A et al (2010) Primary hypothalamic lymphoma in a patient with systemic lupus erythematosus: case report and review of the literature. Neurol Sci 31:647–652. https://doi.org/10.1007/s10072-010-0338-x
Lai GGY, Koo YX, Tao M, Tan TT, Lim ST (2011) Use of rituximab in combination with high-dose methotrexate in the treatment of primary central nervous system lymphoma in a mycophenolate mofetil treated patient with lupus nephritis. Acta Oncol 50:144–145. https://doi.org/10.3109/0284186x.2010.504231
Svobodova B, Hruskova Z, Rysava R, Tesar V (2011) Brain diffuse large B-cell lymphoma in a systemic lupus erythematosus patient treated with immunosuppressive agents including mycophenolate mofetil. Lupus 20:1452–1454. https://doi.org/10.1177/0961203311412413
Tse TPK, Chan ANL, Chan TKT, Po YC (2014) Post-transplantation primary central nervous system lymphoma in a patient with systemic lupus erythematosus and prolonged use of immunosuppressant. Hong Kong Med J 20:541–544. https://doi.org/10.12809/hkmj134095
Turno-Krecicka A, Tomczyk-Socha M, Zimny A (2016) Progressive outer retinal necrosis syndrome in the course of systemic lupus erythematosus. Lupus 25:1610–1614. https://doi.org/10.1177/0961203316646464
Balci MA, Pamuk GE, Unlu E, Usta U, Pamuk ON (2017) Development of primary central nervous system lymphoma in a systemic lupus erythematosus patient after treatment with mycophenolate mofetil and review of the literature. Lupus 26:1224–1227. https://doi.org/10.1177/0961203317691370
Boddu P, Mohammed AS, Annem C, Sequeira W (2017) SLE and non-Hodgkin’s lymphoma: a case series and review of the literature. Case Rep Rheumatol 2017:1658473. https://doi.org/10.1155/2017/1658473
Park SY, Kim SI, Kim H, Lee Y, Park SH (2018) An autopsy case of Epstein-Barr virus-associated diffuse large B-cell lymphoma of the central nervous system in an immunocompromised host. J Pathol Transl Med 52:51–55. https://doi.org/10.4132/jptm.2017.01.23
Su L, Ding ML, Chen LL, Li C, Lao MX (2018) Primary central nervous system lymphoma in a patient with systemic lupus erythematosus mimicking high-grade glioma. A case report and review of literature. Medicine 97:e11072. https://doi.org/10.1097/md.0000000000011072
Fallah M, Liu X, Ji J, Forsti A, Sundquist K, Hemminki K (2014) Autoimmune diseases associated with non-Hodgkin lymphoma: a nationwide cohort study. Ann Oncol 25:2025–2030. https://doi.org/10.1093/annonc/mdu365
Lofstrom B, Backlin C, Sundstrom C, Ekbom A, Lundberg IE (2007) A closer look at non-Hodgkin’s lymphoma cases in a national Swedish systemic lupus erythematosus cohort: a nested case-control study. Ann Rheum Dis 66:1627–1632. https://doi.org/10.1136/ard.2006.067108
Gladman DD, Urowitz MB, Goldsmith CH, Fortin P, Ginzler E, Gordon C et al (1997) The reliability of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index in patients with systemic lupus erythematosus. Arthritis Rheum 40:809–813. https://doi.org/10.1002/art.1780400506
King JK, Costenbader KH (2007) Characteristics of patients with systemic lupus erythematosus (SLE) and non-Hodgkin’s lymphoma (NHL). Clin Rheumatol 26:1491–1494. https://doi.org/10.1007/s10067-006-0532-7
ACR Ad Hoc Committee on Neuropsychiatric Lupus Nomenclature (1999) The American College of Rheumatology nomenclature and case definitions for neuropsychiatric lupus syndromes. Arthritis Rheum 42:599–608. https://doi.org/10.1002/1529-0131(199904)42:4%3c599::aid-anr2%3e3.0.co;2-f
Petri M, Naqibuddin M, Carson KA, Wallace DJ, Weisman MH, Holliday SL et al (2008) Brain magnetic resonance imaging in newly diagnosed systemic lupus erythematosus. J Rheumatol 35:2348–2354. https://doi.org/10.3899/jrheum.071010
Pisetsky DS (2018) Role of Epstein-Barr virus infection in SLE: gene-environment interactions at the molecular level. Ann Rheum Dis 77:1249–1250. https://doi.org/10.1136/annrheumdis-2018-213783
Sugita Y, Muta H, Ohshima K, Morioka M, Tsukamoto Y, Takahashi H et al (2016) Primary central nervous system lymphomas and related diseases: pathological characteristics and discussion of the differential diagnosis. Neuropathology 36:313–324. https://doi.org/10.1111/neup.12276
Harley JB, James JA (2006) Epstein-Barr virus infection induces lupus autoimmunity. Bull NYU Hosp Jt Dis 64:45–50
Draborg AH, Duus K, Houen G (2013) Epstein-Barr virus in systemic autoimmune diseases. Clin Dev Immunol 2013:535738. https://doi.org/10.1155/2013/535738
Abu-Shakra M, Gladman DD, Urowitz MB (1996) Malignancy in systemic lupus erythematosus. Arthritis Rheum 39:1050–1054. https://doi.org/10.1002/art.1780390625
Mao C, Jiang L, Melo-Jorge M, Puthenveetil M, Zhang X, Carroll MC et al (2004) T cell-independent somatic hypermutation in murine B cells with an immature phenotype. Immunity 20:133–144. https://doi.org/10.1016/s1074-7613(04)00019-6
Antinori A, De Rossi G, Ammassari A, Cingolani A, Murri R, Di Giuda D et al (1999) Value of combined approach with thallium-201 single-photon emission computed tomography and Epstein-Barr virus DNA polymerase chain reaction in CSF for the diagnosis of AIDS-related primary CNS lymphoma. J Clin Oncol 17:554–560. https://doi.org/10.1200/jco.1999.17.2.554
Antinori A, Ammassari A, Luzzati R, Castagna A, Maserati R, Rizzardini G et al (2000) Role of brain biopsy in the management of focal brain lesions in HIV-infected patients. Gruppo Italiano Cooperativo AIDS and Tumori. Neurology 54:993–997. https://doi.org/10.1212/wnl.54.4.993
Crane GM, Powell H, Kostadinov R, Rocafort PT, Rifkin DE, Burger PC et al (2015) Primary CNS lymphoproliferative disease, mycophenolate and calcineurin inhibitor usage. Oncotarget 6:33849–33866. https://doi.org/10.18632/oncotarget.5292
Bernatsky S, Joseph L, Boivin JF, Gordon C, Urowitz M, Gladman D et al (2008) The relationship between cancer and medication exposures in systemic lupus erythaematosus: a case-cohort study. Ann Rheum Dis 67:74–79. https://doi.org/10.1136/ard.2006.069039
Schwartz KM, Erickson BJ, Lucchinetti C (2006) Pattern of T2 hypointensity associated with ring-enhancing brain lesions can help to differentiate pathology. Neuroradiology 48:143–149. https://doi.org/10.1007/s00234-005-0024-5
Brandsma D, Bromberg JEC (2018) Primary CNS lymphoma in HIV infection. Handb Clin Neurol 152:177–186. https://doi.org/10.1016/b978-0-444-63849-6.00014-1
Fox CP, Phillips EH, Smith J, Linton K, Gallop-Evans E, Hemmaway C et al (2019) Guidelines for the diagnosis and management of primary central nervous system diffuse large B-cell lymphoma. Br J Haematol 184:348–363. https://doi.org/10.1111/bjh.15661
Ruhstaller TW, Amsler U, Cerny T (2000) Rituximab: active treatment of central nervous system involvement by non-Hodgkin’s lymphoma? Ann Oncol 11:374–375. https://doi.org/10.1023/a:1008371602708
Pettersson T, Pukkala E, Teppo L, Friman C (1992) Increased risk of cancer in patients with systemic lupus erythematosus. Ann Rheum Dis 51:437–439. https://doi.org/10.1136/ard.51.4.437
Wen J, Stock AD, Chalmers SA, Putterman C (2016) The role of B cells and autoantibodies in neuropsychiatric lupus. Autoimmun Rev 15:890–895. https://doi.org/10.1016/j.autrev.2016.07.009
Govoni M, Bortoluzzi A, Padovan M, Silvagni E, Borrelli M, Donelli F et al (2016) The diagnosis and clinical management of the neuropsychiatric manifestations of lupus. J Autoimmun 74:41–72. https://doi.org/10.1016/j.jaut.2016.06.013
Narvaez J, Rios-Rodriguez V, de la Fuente D, Estrada P, Lopez-Vives L, Gomez-Vaquero C et al (2011) Rituximab therapy in refractory neuropsychiatric lupus: current clinical evidence. Semin Arthritis Rheum 41:364–372. https://doi.org/10.1016/j.semarthrit.2011.06.004
Vincent FB, Saulep-Easton D, Figgett WA, Fairfax KA, Mackay F (2013) The BAFF/APRIL system: emerging functions beyond B cell biology and autoimmunity. Cytokine Growth Factor Rev 24:203–215. https://doi.org/10.1016/j.cytogfr.2013.04.003
George-Chandy A, Trysberg E, Eriksson K (2008) Raised intrathecal levels of APRIL and BAFF in patients with systemic lupus erythematosus: relationship to neuropsychiatric symptoms. Arthritis Res Ther 10:R97. https://doi.org/10.1186/ar2484
Birnbaum T, Langer S, Roeber S, von Baumgarten L, Straube A (2013) Expression of B-cell activating factor, a proliferating inducing ligand and its receptors in primary central nervous system lymphoma. Neurol Int 5:e4. https://doi.org/10.4081/ni.2013.e4
Acknowledgements
We wish to thank the members of the Department of Neurosurgery for their efforts in providing medical care. We would like to thank Editage (www.editage.com) for English editing.
Funding
None.
Author information
Authors and Affiliations
Contributions
The diagnosis and medical care were performed by T-I, Y-S, D-K, and Y-S. Radiological evaluation and diagnostic support were provided by T-K. All authors conceived and made the design of this case report. T-I and Y-S prepared the draft of this manuscript. Y-S and Y-S revised the manuscript. All authors approved the final manuscript as submitted and agreed to be responsible for all aspects of this report.
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no financial or personal conflict of interest.
Informed consent
Informed consent was obtained from the patient in this case.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Ichikawa, T., Shimojima, Y., Kishida, D. et al. Primary central nervous system lymphoma in neuropsychiatric systemic lupus erythematosus: case-based review. Rheumatol Int 41, 1009–1017 (2021). https://doi.org/10.1007/s00296-020-04569-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00296-020-04569-6