{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T08:40:21Z","timestamp":1793868021976,"version":"4.6.1"},"reference-count":31,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,4,23]],"date-time":"2024-04-23T00:00:00Z","timestamp":1713830400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,4,23]],"date-time":"2024-04-23T00:00:00Z","timestamp":1713830400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BJC Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Neurolymphomatosis is a lymphoid malignancy of the peripheral nervous system and its natural history is poorly understood.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>We performed PubMed search and extracted clinical data for Kaplan-Meier statistics to determine outcome parameters over time. Kruskal-Wallis test was performed to compare prognostic factors.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Our search identified 559 patients and their median age was 61 years. Median overall survival (OS) was 12.0 (range 10.0\u201315.0) months. Diffuse large B-cell lymphoma was the most frequent histology, involving the brachial plexus, cranial nerves, and sciatic nerve. None had molecular profiling. There was a progressive lengthening of OS in successive decades, from 0.5 (95% CI 0.0\u20130.8) to 26.4 (95% CI 18.0\u201334.8) months between 1951 and 2022 (r<jats:sup>2<\/jats:sup>\u2009=\u20090.0528, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.00001). Time from first treatment (treatment 1) to progression increased from 2.0 to 36.0 (95% CI 6.5\u201350.7) months (r<jats:sup>2<\/jats:sup>\u2009=\u20090.0961, <jats:italic>p<\/jats:italic>\u2009=\u20090.00236). Time from symptom onset to diagnosis remained unchanged (r<jats:sup>2<\/jats:sup>\u2009=\u20090.0000556, <jats:italic>p<\/jats:italic>\u2009=\u20090.939). Patients were most frequently treated with methotrexate, rituximab, and\/or radiation either alone or in combination. Primary neurolymphomatosis had a better prognosis than secondary neurolymphomatosis. No OS difference was noted between B- and T-cell disease, but low-grade B-cell performed better than Burkitt\u2019s lymphoma.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Discussion<\/jats:title>\n                <jats:p>Better outcome for patients with neurolymphomatosis is noted over time. But timely diagnosis remains a major problem that needs improvement.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1038\/s44276-024-00053-x","type":"journal-article","created":{"date-parts":[[2024,4,23]],"date-time":"2024-04-23T12:01:49Z","timestamp":1713873709000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["The natural history of neurolymphomatosis"],"prefix":"10.1038","volume":"2","author":[{"given":"Elizabeth","family":"Xu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quan","family":"Ho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiva","family":"Gautam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric T.","family":"Wong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,4,23]]},"reference":[{"key":"53_CR1","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1093\/neuonc\/5.2.104","volume":"5","author":"JM Baehring","year":"2003","unstructured":"Baehring JM, Damek D, Martin EC, Betensky RA, Hochberg FH. Neurolymphomatosis. Neuro-Oncol. 2003;5:104\u201315. https:\/\/doi.org\/10.1093\/neuonc\/5.2.104","journal-title":"Neuro-Oncol"},{"key":"53_CR2","first-page":"281","volume":"39","author":"LN Payne","year":"1967","unstructured":"Payne LN, Biggs PM. Studies on Marek\u2019s disease. II. Pathogenesis. J Natl Cancer Inst. 1967;39:281\u2013302.","journal-title":"J Natl Cancer Inst."},{"key":"53_CR3","doi-asserted-by":"publisher","first-page":"952","DOI":"10.1073\/pnas.64.3.952","volume":"64","author":"LF Lee","year":"1969","unstructured":"Lee LF, B Roizman B, Spear PG, Kieff ED, Burmester BR, Nazerian K. Marek\u2019s disease herpes virus: a cytomegalovirus. Proc Natl Acad Sci USA. 1969;64:952\u20136. https:\/\/doi.org\/10.1073\/pnas.64.3.952","journal-title":"Proc Natl Acad Sci USA"},{"key":"53_CR4","doi-asserted-by":"publisher","first-page":"5005","DOI":"10.1182\/blood-2009-12-258210","volume":"115","author":"S Grisariu","year":"2010","unstructured":"Grisariu S, Avni B, Batchelor TT, van den Bent MJ, Bokstein F, Schiff D, et al. Neurolymphomatosis: an international primary CNS lymphoma collaborative group report. Blood. 2010;115:5005\u201311. https:\/\/doi.org\/10.1182\/blood-2009-12-258210","journal-title":"Blood"},{"key":"53_CR5","doi-asserted-by":"publisher","first-page":"1379","DOI":"10.1182\/bloodadvances.2020003666","volume":"5","author":"A Khurana","year":"2021","unstructured":"Khurana A, NovoM, Nowakowski GS, Ristow KM, Spinner RJ, Hunt CH, et al. Clinical manifestations of, diagnostic approach to, and treatment of neurolymphomatosis in the rituximab era. Blood Adv. 2021;5:1379\u201387. https:\/\/doi.org\/10.1182\/bloodadvances.2020003666","journal-title":"Blood Adv"},{"key":"53_CR6","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1007\/s11060-004-3389-0","volume":"72","author":"F Bokstein","year":"2005","unstructured":"Bokstein F, Goor O, Shihman B, Rochkind S, Even-Sapir E, Metser U, et al. Assessment of neurolymphomatosis by brachial plexus biopsy and PET\/CT. Report of a case. J Neurooncol. 2005;72:163\u20137. https:\/\/doi.org\/10.1007\/s11060-004-3389-0","journal-title":"J Neurooncol"},{"key":"53_CR7","doi-asserted-by":"publisher","first-page":"93","DOI":"10.5692\/clinicalneurol.cn-001080","volume":"58","author":"A Asanome","year":"2018","unstructured":"Asanome A, Kano K, Takahashi K, Saito T, Sawada J, Katayama T. A case of neurolymphomatosis that was diagnosed by acoustic nerve biopsy. Rinsho Shinkeigaku. 2018;58:93\u201399. https:\/\/doi.org\/10.5692\/clinicalneurol.cn-001080","journal-title":"Rinsho Shinkeigaku"},{"key":"53_CR8","first-page":"57","volume":"2","author":"NX Canh","year":"2014","unstructured":"Canh NX, Tan NV, Tung TT, Son NT, Maurea S. (18)F-FDG PET\/CT in neurolymphomatosis: report of 3 cases. Asia Ocean J Nucl Med Biol. 2014;2:57\u201364.","journal-title":"Asia Ocean J Nucl Med Biol"},{"key":"53_CR9","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1007\/s11060-008-9633-2","volume":"90","author":"N Levin","year":"2008","unstructured":"Levin N, Soffer D, Grissaru S, Aizikovich N, Gomori JM, Siegal T. Primary T-cell CNS lymphoma presenting with leptomeningeal spread and neurolymphomatosis. J Neurooncol. 2008;90:77\u201383. https:\/\/doi.org\/10.1007\/s11060-008-9633-2","journal-title":"J Neurooncol"},{"key":"53_CR10","doi-asserted-by":"publisher","first-page":"617","DOI":"10.1002\/mus.27045","volume":"62","author":"S Keddie","year":"2020","unstructured":"Keddie S, Nagendran A, Cox T, Bomsztyk J, Jaunmuktane Z, Brandner S, et al. Peripheral nerve neurolymphomatosis: clinical features, treatment, and outcomes. Muscle Nerve. 2020;62:617\u201325. https:\/\/doi.org\/10.1002\/mus.27045","journal-title":"Muscle Nerve"},{"key":"53_CR11","first-page":"435","volume":"6","author":"AW Maksymiuk","year":"1996","unstructured":"Maksymiuk AW, Haines C, Tan LK, Skinnider LF. Age-related prognostic factor analysis in non-Hodgkin\u2019s lymphoma. Can J Oncol. 1996;6:435\u201342.","journal-title":"Can J Oncol"},{"key":"53_CR12","doi-asserted-by":"publisher","first-page":"e1027","DOI":"10.1212\/wnl.0000000000008900","volume":"94","author":"C Houillier","year":"2020","unstructured":"Houillier C, Soussain C, Ghesqui\u00e8res H, Soubeyran P, Chinot O, Taillandier L, et al. Management and outcome of primary CNS lymphoma in the modern era: an LOC network study. Neurology. 2020;94:e1027\u201339. https:\/\/doi.org\/10.1212\/wnl.0000000000008900","journal-title":"Neurology"},{"key":"53_CR13","doi-asserted-by":"publisher","first-page":"1403","DOI":"10.1182\/blood-2014-10-604561","volume":"125","author":"A Omuro","year":"2015","unstructured":"Omuro A, Correa DD, DeAngelis LM, Moskowitz CH, Matasar MJ, Kaley TJ, et al. R-MPV followed by high-dose chemotherapy with TBC and autologous stem-cell transplant for newly diagnosed primary CNS lymphoma. Blood. 2015;125:1403\u201310. https:\/\/doi.org\/10.1182\/blood-2014-10-604561","journal-title":"Blood"},{"key":"53_CR14","doi-asserted-by":"publisher","first-page":"3971","DOI":"10.1200\/jco.2013.50.4910","volume":"31","author":"PG Morris","year":"2013","unstructured":"Morris PG, Correa DD, Yahalom J, Raizer JJ, Schiff D, Grantet B, et al. Rituximab, methotrexate, procarbazine, and vincristine followed by consolidation reduced-dose whole-brain radiotherapy and cytarabine in newly diagnosed primary CNS lymphoma: final results and long-term outcome. J Clin Oncol. 2013;31:3971\u20139. https:\/\/doi.org\/10.1200\/jco.2013.50.4910","journal-title":"J Clin Oncol"},{"key":"53_CR15","doi-asserted-by":"publisher","first-page":"1010","DOI":"10.1002\/cam4.269","volume":"3","author":"E Fonkem","year":"2014","unstructured":"Fonkem E, Lok E, Robison D, Gautam S, Wong ET. The natural history of intravascular lymphomatosis. Cancer Med. 2014;3:1010\u201324. https:\/\/doi.org\/10.1002\/cam4.269","journal-title":"Cancer Med"},{"key":"53_CR16","doi-asserted-by":"publisher","first-page":"274","DOI":"10.3988\/jcn.2016.12.3.274","volume":"12","author":"R Shree","year":"2016","unstructured":"Shree R, Goyal MK, Modi M, Gaspar BL, Radotra BD, Ahuja CK, et al. The diagnostic dilemma of neurolymphomatosis. J Clin Neurol. 2016;12:274\u201381. https:\/\/doi.org\/10.3988\/jcn.2016.12.3.274","journal-title":"J Clin Neurol"},{"key":"53_CR17","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1038\/modpathol.2009.164","volume":"23","author":"EM Hattab","year":"2010","unstructured":"Hattab EM, Martin SE, Al-Khatib SM, Kupsky WJ, Vance GH, Stohler RA, et al. Most primary central nervous system diffuse large B-cell lymphomas occurring in immunocompetent individuals belong to the nongerminal center subtype: a retrospective analysis of 31 cases. Mod Pathol. 2010;23:235\u201343. https:\/\/doi.org\/10.1038\/modpathol.2009.164","journal-title":"Mod Pathol"},{"key":"53_CR18","doi-asserted-by":"publisher","first-page":"80","DOI":"10.3109\/02688697.2015.1071328","volume":"30","author":"J Jelicic","year":"2016","unstructured":"Jelicic J, Balint MT, Raicevic S, Ilic R, Stanisavljevic D, Bila J, et al. The possible benefit from total tumour resection in primary diffuse large B-cell lymphoma of central nervous system\u2014a one-decade single-centre experience. Br J Neurosurg. 2016;30:80\u20135. https:\/\/doi.org\/10.3109\/02688697.2015.1071328","journal-title":"Br J Neurosurg."},{"key":"53_CR19","doi-asserted-by":"publisher","first-page":"e1436","DOI":"10.1016\/j.wneu.2019.02.252","volume":"126","author":"CM Labak","year":"2019","unstructured":"Labak CM, Holdhoff M, Bettegowda C, Gallia GL, Lim M, Weingart JD, et al. Surgical resection for primary central nervous system lymphoma: a systematic review. World Neurosurg. 2019;126:e1436\u201348. https:\/\/doi.org\/10.1016\/j.wneu.2019.02.252","journal-title":"World Neurosurg"},{"key":"53_CR20","doi-asserted-by":"publisher","DOI":"10.1186\/s12883-021-02227-3","volume":"21","author":"S Wu","year":"2021","unstructured":"Wu S, Wang J, Liu W, Hu F, Zhao K, Jiang W, et al. The role of surgical resection in primary central nervous system lymphoma: a single-center retrospective analysis of 70 patients. BMC Neurol. 2021;21:190. https:\/\/doi.org\/10.1186\/s12883-021-02227-3","journal-title":"BMC Neurol"},{"key":"53_CR21","doi-asserted-by":"publisher","first-page":"3061","DOI":"10.1200\/JCO.2012.46.9957","volume":"31","author":"JL Rubenstein","year":"2013","unstructured":"Rubenstein JL, Hsi ED, Johnson JL, Jung SH, Nakashima MO, Grant B, et al. Intensive chemotherapy and immunotherapy in patients with newly diagnosed primary CNS lymphoma: CALGB 50202 (Alliance 50202). J Clin Oncol. 2013;31:3061\u20138. https:\/\/doi.org\/10.1200\/JCO.2012.46.9957","journal-title":"J Clin Oncol"},{"key":"53_CR22","doi-asserted-by":"publisher","first-page":"4730","DOI":"10.1200\/JCO.2007.12.5062","volume":"25","author":"GD Shah","year":"2007","unstructured":"Shah GD, Yahalom J, Correa DD, Lai RK, Raizer JJ, Schiff D, et al. Combined immunochemotherapy with reduced whole-brain radiotherapy for newly diagnosed primary CNS lymphoma. J Clin Oncol. 2007;25:4730. https:\/\/doi.org\/10.1200\/JCO.2007.12.5062","journal-title":"J Clin Oncol"},{"key":"53_CR23","doi-asserted-by":"publisher","first-page":"e510","DOI":"10.1016\/S2352-3026(17)30174-6","volume":"4","author":"AJM Ferreri","year":"2017","unstructured":"Ferreri AJM, Cwynarski K, Pulczynski E, Fox CP, Schorb E, La Ros\u00e9e P, et al. Whole-brain radiotherapy or autologous stem-cell transplantation as consolidation strategies after high-dose methotrexate-based chemoimmunotherapy in patients with primary CNS lymphoma: results of the second randomisation of the International Extranodal Lymphoma Study Group-32 phase 2 trial. Lancet Haematol. 2017;4:e510\u2013e523. https:\/\/doi.org\/10.1016\/S2352-3026(17)30174-6","journal-title":"Lancet Haematol"},{"key":"53_CR24","doi-asserted-by":"publisher","first-page":"823","DOI":"10.1200\/JCO.18.00306","volume":"37","author":"C Houillier","year":"2019","unstructured":"Houillier C, Taillandier L, Dureau S, Lamy T, Laadhari M, Chinot O, et al. Radiotherapy or autologous stem-cell transplantation for primary CNS lymphoma in patients 60 years of age and younger: results of the intergroup ANOCEF-GOELAMS randomized phase II PRECIS study. J Clin Oncol. 2019;37:823\u201333. https:\/\/doi.org\/10.1200\/JCO.18.00306","journal-title":"J Clin Oncol"},{"key":"53_CR25","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1023\/a:1022588812415","volume":"61","author":"JM Baehring","year":"2003","unstructured":"Baehring JM, Longtine J, Hochberg FH. A new approach to the diagnosis and treatment of intravascular lymphoma. J Neurooncol. 2003;61:237\u201348. https:\/\/doi.org\/10.1023\/a:1022588812415","journal-title":"J Neurooncol"},{"key":"53_CR26","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1016\/s0046-8177(00)80223-3","volume":"31","author":"M Ponzoni","year":"2000","unstructured":"Ponzoni M, Arrigoni G, Gould VE, Del Curto B, Maggioni M, Scapinello A, et al. Lack of CD 29 (beta1 integrin) and CD 54 (ICAM-1) adhesion molecules in intravascular lymphomatosis. Hum Pathol. 2000;31:220\u20136. https:\/\/doi.org\/10.1016\/s0046-8177(00)80223-3","journal-title":"Hum Pathol"},{"key":"53_CR27","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1007\/s11060-011-0575-8","volume":"105","author":"M Lun","year":"2011","unstructured":"Lun M, Lok E, Gautam S, Wu E, Wong ET. The natural history of extracranial metastasis from glioblastoma multiforme. J Neurooncol. 2011;105:261\u201373. https:\/\/doi.org\/10.1007\/s11060-011-0575-8","journal-title":"J Neurooncol"},{"key":"53_CR28","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1093\/nop\/npaa083","volume":"8","author":"EK Noch","year":"2021","unstructured":"Noch EK, Sait SF, Farooq S, Trippett TM, Miller AM. A case series of extraneural metastatic glioblastoma at Memorial Sloan Kettering Cancer Center. Neurooncol Pract. 2021;8:325\u201336. https:\/\/doi.org\/10.1093\/nop\/npaa083","journal-title":"Neurooncol Pract"},{"key":"53_CR29","doi-asserted-by":"publisher","first-page":"1043","DOI":"10.1007\/s00256-019-3145-3","volume":"48","author":"AH DeVries","year":"2019","unstructured":"DeVries AH, Howe BM, Spinner RJ, Broski SM. B-cell peripheral neurolymphomatosis: MRI and 18F-FDG PET\/CT imaging characteristics. Skeletal Radiol. 2019;48:1043\u201350. https:\/\/doi.org\/10.1007\/s00256-019-3145-3","journal-title":"Skeletal Radiol"},{"key":"53_CR30","doi-asserted-by":"publisher","first-page":"105340","DOI":"10.1016\/j.clineuro.2019.04.019","volume":"184","author":"C Mau","year":"2019","unstructured":"Mau C, Ghali MGZ, Styler M, Malysz J, Specht CS, Rizk E. Neuroleukemiosis: diagnosis and management. Clin Neurol Neurosurg. 2019;184:105340. https:\/\/doi.org\/10.1016\/j.clineuro.2019.04.019.","journal-title":"Clin Neurol Neurosurg."},{"key":"53_CR31","doi-asserted-by":"publisher","first-page":"2405","DOI":"10.3109\/10428194.2012.691480","volume":"53","author":"CG Reddy","year":"2012","unstructured":"Reddy CG, Mauermann ML, Solomon BM, Ringler MD, Jerath NU, Begna KH, et al. Neuroleukemiosis: an unusual cause of peripheral neuropathy. Leuk Lymphoma. 2012;53:2405\u201311. https:\/\/doi.org\/10.3109\/10428194.2012.691480","journal-title":"Leuk Lymphoma."}],"container-title":["BJC Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s44276-024-00053-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s44276-024-00053-x","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s44276-024-00053-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,23]],"date-time":"2024-04-23T12:20:37Z","timestamp":1713874837000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s44276-024-00053-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,23]]},"references-count":31,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["53"],"URL":"https:\/\/doi.org\/10.1038\/s44276-024-00053-x","relation":{},"ISSN":["2731-9377"],"issn-type":[{"value":"2731-9377","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,23]]},"assertion":[{"value":"6 December 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 February 2024","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 March 2024","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 April 2024","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"Not applicable. This is a retrospective analysis using open-source information.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}}],"article-number":"34"}}