Abstract
Primary central nervous system lymphomas (PCNSLs) classically remain confined within the CNS throughout their evolution for unknown reasons. Our objective was to analyse the rare extracerebral relapses of PCNSL in a nationwide population-based study. We retrospectively selected PCNSL patients who experienced extracerebral relapse during their follow-up from the French LOC database. Of the 1968 PCNSL included in the database from 2011, 30 (1.5%, median age 71 years, median KPS 70) presented an extracerebral relapse, either pure (n = 20) or mixed (both extracerebral and in the CNS) (n = 10), with a histological confirmation in 20 cases. The median delay between initial diagnosis and systemic relapse was 15.5 months [2-121 months]. We found visceral (n = 23, 77%), including testis in 5 (28%) men and breast in 3 (27%) women, lymph node (n = 12, 40%), and peripheral nervous system (PNS) (n = 7, 23%) involvement. Twenty-seven patients were treated with chemotherapy, either with only systemic targets (n = 7) or mixed systemic and CNS targets (n = 20), 4 were consolidated by HCT-ASCT. After systemic relapse, the median progression-free survival and overall survival (OS) were 7 and 12 months, respectively. KPS > 70 and pure systemic relapses were significantly associated with higher OS. Extracerebral PCNSL relapses are rare, mainly extranodal, and frequently involve the testis, breast, and PNS. The prognosis was worse in mixed relapses. Early relapses raise the question of misdiagnosed occult extracerebral lymphoma at diagnostic workup that should systematically include a PET-CT. Paired tumour analysis at diagnosis/relapse would provide a better understanding of the underlying molecular mechanisms.
Similar content being viewed by others
References
Ostrom QT, Gittleman H, Truitt G et al (2018) CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 2011–2015. Neuro Oncol 20:iv1–iv86. https://doi.org/10.1093/neuonc/noy131
Abrey LE, Batchelor TT, Ferreri AJM et al (2005) Report of an international workshop to standardize baseline evaluation and response criteria for primary CNS lymphoma. J Clin Oncol 23:5034–5043. https://doi.org/10.1200/JCO.2005.13.524
Hoang-Xuan K, Bessell E, Bromberg J et al (2015) Diagnosis and treatment of primary CNS lymphoma in immunocompetent patients: guidelines from the European Association for Neuro-Oncology. Lancet Oncol 16:e322–e332. https://doi.org/10.1016/S1470-2045(15)00076-5
Bertaux M, Houillier C, Edeline V et al (2020) Use of FDG-PET/CT for systemic assessment of suspected primary central nervous system lymphoma: a LOC study. J Neurooncol 148:343–352. https://doi.org/10.1007/s11060-020-03525-5
Barajas RF, Politi LS, Anzalone N et al (2021) Consensus recommendations for MRI and PET imaging of primary central nervous system lymphoma: guideline statement from the International Primary CNS Lymphoma Collaborative Group (IPCG). Neuro Oncol 23:1056–1071. https://doi.org/10.1093/neuonc/noab020
DeAngelis LM, Seiferheld W, Schold SC et al (2002) Combination chemotherapy and radiotherapy for primary central nervous system lymphoma: Radiation Therapy Oncology Group study 93-10. J Clin Oncol 20:4643–4648. https://doi.org/10.1200/JCO.2002.11.013
Shan Y, Hu Y (2018) Prognostic factors and survival in primary central nervous system lymphoma: a population-based study. Dis Markers 2018:7860494. https://doi.org/10.1155/2018/7860494
Abrey LE, Ben-Porat L, Panageas KS et al (2006) Primary central nervous system lymphoma: The Memorial Sloan-Kettering Cancer Center prognostic model. JCO 24:5711–5715. https://doi.org/10.1200/JCO.2006.08.2941
Houillier C, Soussain C, Ghesquières H et al (2020) Management and outcome of primary CNS lymphoma in the modern era. Neurology 94:e1027–e1039. https://doi.org/10.1212/WNL.0000000000008900
Langner-Lemercier S, Houillier C, Soussain C et al (2016) Primary CNS lymphoma at first relapse/progression: characteristics, management, and outcome of 256 patients from the French LOC network. Neuro Oncol 18:1297–1303. https://doi.org/10.1093/neuonc/now033
Jahnke K, Thiel E, Martus P et al (2006) Relapse of primary central nervous system lymphoma: clinical features, outcome and prognostic factors. J Neurooncol 80:159–165. https://doi.org/10.1007/s11060-006-9165-6
Provencher S, Ferlay C, Alaoui-Slimani K et al (2011) Clinical characteristics and outcome of isolated extracerebral relapses of primary central nervous system lymphoma: a case series. Hematol Oncol 29:10–16. https://doi.org/10.1002/hon.944
Cheson BD (2015) Staging and response assessment in lymphomas: the new Lugano classification. Chinese Clinical Oncology 4:9
Rosenberg SA (1977) Validity of the Ann Arbor staging classification for the non-Hodgkin’s lymphomas. Cancer Treat Rep 61:1023–1027
Castillo JJ, Winer ES, Olszewski AJ (2014) Sites of extranodal involvement are prognostic in patients with diffuse large B-cell lymphoma in the rituximab era: an analysis of the Surveillance, Epidemiology and End Results database. Am J Hematol 89:310–314. https://doi.org/10.1002/ajh.23638
Kridel R, Telio D, Villa D et al (2017) Diffuse large B-cell lymphoma with testicular involvement: outcome and risk of CNS relapse in the rituximab era. Br J Haematol 176:210–221. https://doi.org/10.1111/bjh.14392
Gholam D, Bibeau F, El Weshi A et al (2003) Primary breast lymphoma. Leukemia & Lymphoma 44:1173–1178. https://doi.org/10.1080/1042819031000079195
Chapuy B, Roemer MGM, Stewart C et al (2016) Targetable genetic features of primary testicular and primary central nervous system lymphomas. Blood 127:869–881. https://doi.org/10.1182/blood-2015-10-673236
Grisariu S, Avni B, Batchelor TT et al (2010) Neurolymphomatosis: an International Primary CNS Lymphoma Collaborative Group report. Blood 115:5005–5011. https://doi.org/10.1182/blood-2009-12-258210
Gogia A, Das CK, Kumar L et al (2018) Diffuse large B-cell lymphoma: an institutional analysis. South Asian J Cancer 7:200–202. https://doi.org/10.4103/sajc.sajc_65_18
Møller MB, Pedersen NT, Christensen BE (2004) Diffuse large B-cell lymphoma: clinical implications of extranodal versus nodal presentation – a population-based study of 1575 cases. Br J Haematol 124:151–159. https://doi.org/10.1046/j.1365-2141.2003.04749.x
International Non-Hodgkin’s Lymphoma Prognostic Factors Project (1993) A predictive model for aggressive non-Hodgkin’s lymphoma. N Engl J Med 329:987–994. https://doi.org/10.1056/NEJM199309303291402
Park HY, Suh CH, Huang RY et al (2021) Diagnostic yield of body CT and whole-body FDG PET/CT for initial systemic staging in patients with suspected primary CNS lymphoma: a systematic review and meta-analysis. Am J Roentgenol 216:1172–1182. https://doi.org/10.2214/AJR.20.24036
Mohile NA, DeAngelis LM, Abrey LE (2008) The utility of body FDG PET in staging primary central nervous system lymphoma. Neuro Oncol 10:223–228. https://doi.org/10.1215/15228517-2007-061
Gupta T, Manjali JJ, Kannan S et al (2021) Diagnostic performance of pretreatment 18F-fluorodeoxyglucose positron emission tomography with or without computed tomography in patients with primary central nervous system lymphoma: updated systematic review and diagnostic test accuracy meta-analyses. Clin Lymphoma Myeloma Leuk 21:497–507. https://doi.org/10.1016/j.clml.2021.03.011
Guedj E, Varrone A, Boellaard R et al (2022) EANM procedure guidelines for brain PET imaging using [18F]FDG, version 3. Eur J Nucl Med Mol Imaging 49:632–651. https://doi.org/10.1007/s00259-021-05603-w
Jahnke K, Hummel M, Korfel A, et al (2006) Detection of subclinical systemic disease in primary CNS lymphoma by polymerase chain reaction of the rearranged immunoglobulin heavy-chain genes. JCO 24:4754–4757. https://doi.org/10.1200/JCO.2006.06.7165
Illerhaus G, Kasenda B, Ihorst G et al (2016) High-dose chemotherapy with autologous haemopoietic stem cell transplantation for newly diagnosed primary CNS lymphoma: a prospective, single-arm, phase 2 trial. The Lancet Haematology 3:e388–e397. https://doi.org/10.1016/S2352-3026(16)30050-3
Ferreri AJM, Blay J-Y, Reni M et al (2003) Prognostic scoring system for primary CNS lymphomas: the International Extranodal Lymphoma Study Group experience. JCO 21:266–272. https://doi.org/10.1200/JCO.2003.09.139
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
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
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.
About this article
Cite this article
Dufour, J., Choquet, S., Hoang-Xuan, K. et al. Systemic relapses of primary CNS lymphomas (PCNSL): a LOC network study. Ann Hematol 102, 1159–1169 (2023). https://doi.org/10.1007/s00277-023-05108-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00277-023-05108-6