{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T14:20:06Z","timestamp":1785162006756,"version":"3.55.0"},"reference-count":45,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2023,11,24]],"date-time":"2023-11-24T00:00:00Z","timestamp":1700784000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Primary lymphoma of the central nervous system (PCNSL) encompasses a variety of lymphoma subtypes, with the majority being diffuse large B-cell lymphomas, which require aggressive systemic treatment. In contrast, low-grade lymphomas are reported infrequently and are mostly limited to dural manifestations. Very rarely, parenchymal low-grade PCNSL is diagnosed, and the cases documented in the literature show a wide variety of treatment approaches. Methods: We screened all cases of PCNSL treated at our department (a tertiary hematooncology and neurooncology center) in the last 15 years and conducted a comprehensive literature research in the PubMed database. Results: Overall, two cases of low-grade primary parenchymal PCNSL treated with irradiation were identified. The dose prescriptions ranged from 30.6 to 36 Gy for the involved site, with sparing of the hippocampal structures. Both patients had an excellent response to the treatment with a mean follow-up of 20 months. No clinical or radiological signs of treatment toxicity were detected. Conclusions: Our analysis corroborates the results from the literature and demonstrates that parenchymal low-grade PCNSL shows a good response to localized radiation treatment, enabling a favorable outcome while avoiding long-term treatment toxicity.<\/jats:p>","DOI":"10.3390\/cancers15235564","type":"journal-article","created":{"date-parts":[[2023,11,24]],"date-time":"2023-11-24T03:43:59Z","timestamp":1700797439000},"page":"5564","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Involved-Site Radiation Therapy Enables Effective Disease Control in Parenchymal Low-Grade Primary Cerebral Lymphoma"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5917-4203","authenticated-orcid":false,"given":"Niklas Benedikt","family":"Pepper","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology, University Hospital Muenster, 48149 Muenster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2786-7013","authenticated-orcid":false,"given":"Michael","family":"Oertel","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, University Hospital Muenster, 48149 Muenster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4869-5986","authenticated-orcid":false,"given":"Gabriele","family":"Reinartz","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, University Hospital Muenster, 48149 Muenster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9303-7336","authenticated-orcid":false,"given":"Khaled","family":"Elsayad","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, University Hospital Muenster, 48149 Muenster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5131-1859","authenticated-orcid":false,"given":"Dominik Alexander","family":"Hering","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, University Hospital Muenster, 48149 Muenster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatih","family":"Yalcin","sequence":"additional","affiliation":[{"name":"Department of Pathology, University Hospital Schleswig-Holstein, 24105 Kiel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7228-6963","authenticated-orcid":false,"given":"Moritz","family":"Wildgruber","sequence":"additional","affiliation":[{"name":"Department for Radiology, University Hospital Munich, LMU Munich, 81377 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter","family":"Stummer","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University Hospital Muenster, 48149 Muenster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georg","family":"Lenz","sequence":"additional","affiliation":[{"name":"Department of Hematology, Oncology and Pneumology, University Hospital Muenster, 48149 Muenster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfram","family":"Klapper","sequence":"additional","affiliation":[{"name":"Department of Pathology, University Hospital Schleswig-Holstein, 24105 Kiel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans Theodor","family":"Eich","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, University Hospital Muenster, 48149 Muenster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,24]]},"reference":[{"key":"ref_1","unstructured":"Deckert, M., Batchelor, T., Ferry, J.A., Hoang-Xuan, K., Nagane, M., Paulus, W., and Weller, M. (2021). Primary Diffuse Large B-Cell Lymphoma of the CNS, World Health Organization Classification of Tumours of the Central Nervous System 2021, WHO Classification of Tumours Series."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1093\/neuonc\/noac196","article-title":"European Association of Neuro-Oncology (EANO) Guidelines for Treatment of Primary Central Nervous System Lymphoma (PCNSL)","volume":"25","author":"Deckert","year":"2023","journal-title":"Neuro-Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1093\/neuonc\/noy192","article-title":"Comprehensive Approach to Diagnosis and Treatment of Newly Diagnosed Primary CNS Lymphoma","volume":"21","author":"Grommes","year":"2019","journal-title":"Neuro-Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1093\/neuonc\/nox187","article-title":"The Elderly Left behind\u2014Changes in Survival Trends of Primary Central Nervous System Lymphoma over the Past 4 Decades","volume":"20","author":"Mendez","year":"2018","journal-title":"Neuro-Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1212\/01.WNL.0000109673.75316.D8","article-title":"Cognitive Functions in Survivors of Primary Central Nervous System Lymphoma","volume":"62","author":"Correa","year":"2004","journal-title":"Neurology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1212\/WNL.62.4.544","article-title":"Cognitive Status and Quality of Life after Treatment for Primary CNS Lymphoma","volume":"62","author":"Harder","year":"2004","journal-title":"Neurology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1815","DOI":"10.1007\/s00432-017-2423-5","article-title":"Early Whole Brain Radiotherapy in Primary CNS Lymphoma: Negative Impact on Quality of Life in the Randomized G-PCNSL-SG1 Trial","volume":"143","author":"Herrlinger","year":"2017","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2501","DOI":"10.1200\/JCO.2020.38.15_suppl.2501","article-title":"Randomized Phase II Study of Rituximab, Methotrexate (MTX), Procarbazine, Vincristine, and Cytarabine (R-MPV-A) with and without Low-Dose Whole-Brain Radiotherapy (LD-WBRT) for Newly Diagnosed Primary CNS Lymphoma (PCNSL)","volume":"38","author":"Omuro","year":"2020","journal-title":"JCO"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.1016\/S1470-2045(10)70229-1","article-title":"High-Dose Methotrexate with or without Whole Brain Radiotherapy for Primary CNS Lymphoma (G-PCNSL-SG-1): A Phase 3, Randomised, Non-Inferiority Trial","volume":"11","author":"Thiel","year":"2010","journal-title":"Lancet Oncol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2811","DOI":"10.1002\/cncr.32834","article-title":"Primary Dural Lymphomas: Clinical Presentation, Management, and Outcome","volume":"126","author":"Karschnia","year":"2020","journal-title":"Cancer"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1111\/j.1365-2141.2004.05361.x","article-title":"Low-Grade Primary Central Nervous System Lymphoma in Immunocompetent Patients","volume":"128","author":"Jahnke","year":"2005","journal-title":"Br. J. Haematol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1007\/s11060-022-04052-1","article-title":"Chemotherapy Is an Efficient Treatment in Primary CNS MALT Lymphoma","volume":"159","author":"Desjardins","year":"2022","journal-title":"J. Neurooncol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"305","DOI":"10.3816\/CLM.2008.n.043","article-title":"Primary Central Nervous System Marginal Zone B-Cell Lymphoma of the Basal Ganglia Mimicking Low-Grade Glioma: A Case Report and Review of the Literature","volume":"8","author":"Park","year":"2008","journal-title":"Clin. Lymphoma Myeloma"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.1007\/s00277-011-1225-0","article-title":"Primary CNS Lymphoma Other than DLBCL: A Descriptive Analysis of Clinical Features and Treatment Outcomes","volume":"90","author":"Lim","year":"2011","journal-title":"Ann. Hematol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1111\/j.1440-1789.2012.01350.x","article-title":"Central Nervous System Marginal Zone B-Cell Lymphoma of Mucosa-Associated Lymphoid Tissue Type Involving the Brain and Spinal Cord Parenchyma: Non-Dural Marginal Zone B-Cell Lymphoma","volume":"33","author":"Ueba","year":"2013","journal-title":"Neuropathology"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2015","DOI":"10.1016\/j.jocn.2014.04.013","article-title":"\u201cBrain on Fire\u201d: A New Imaging Sign","volume":"21","author":"Epaliyanage","year":"2014","journal-title":"J. Clin. Neurosci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"5718","DOI":"10.1200\/JCO.2005.17.624","article-title":"Clinicopathologic and Genetic Profile of Intracranial Marginal Zone Lymphoma: A Primary Low-Grade CNS Lymphoma That Mimics Meningioma","volume":"23","author":"Tu","year":"2005","journal-title":"JCO"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"55","DOI":"10.4236\/ojpathology.2013.32010","article-title":"Primary CNS Marginal Zone Lymphoma: A Case Report and Review of the Literature","volume":"03","author":"Aqil","year":"2013","journal-title":"Open J. Pathol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"43","DOI":"10.3324\/haematol.2016.147728","article-title":"Guideline for the Diagnosis, Treatment and Response Criteria for Bing-Neel Syndrome","volume":"102","author":"Minnema","year":"2017","journal-title":"Haematologica"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1182\/blood-2018-04-843540","article-title":"Definitive Radiotherapy for Localized Follicular Lymphoma Staged by 18F-FDG PET-CT: A Collaborative Study by ILROG","volume":"133","author":"Brady","year":"2019","journal-title":"Blood"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1007\/s00066-019-01538-2","article-title":"Radiotherapy of Extranodal Low-Grade Follicular and Marginal Zone Lymphomas: Long-Term Follow-up of 159 Patients","volume":"196","author":"Elsayad","year":"2020","journal-title":"Strahlenther. Onkol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e155","DOI":"10.1016\/j.leukres.2012.03.022","article-title":"Extranodal Marginal Zone Lymphoma of the CNS Arising after a Long-Standing History of Atypical White Matter Disease","volume":"36","author":"Schiefer","year":"2012","journal-title":"Leuk. Res."},{"key":"ref_23","first-page":"89","article-title":"Rare Case of a Primary Non-Dural Central Nervous System Low Grade B-Cell Lymphoma and Literature Review","volume":"5","author":"Wang","year":"2012","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.anorl.2017.12.002","article-title":"Meningeal Marginal Zone B-Cell Lymphoma: The Meningioma Trap","volume":"135","author":"Villeneuve","year":"2018","journal-title":"Eur. Ann. Otorhinolaryngol. Head. Neck Dis."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1007\/s11060-006-9153-x","article-title":"Extranodal Marginal Zone B-Cell Lymphoma Mimicking Meningioma in Lateral Ventricle: A Case Report and Possible Pathogenesis","volume":"80","author":"Jung","year":"2006","journal-title":"J. Neurooncol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2125","DOI":"10.1038\/s41598-020-80724-0","article-title":"High-Dose Methotrexate-Based Regimens and Post-Remission Consolidation for Treatment of Newly Diagnosed Primary CNS Lymphoma: Meta-Analysis of Clinical Trials","volume":"11","author":"Yu","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Karsten, I.E., Reinartz, G., Pixberg, M., Kr\u00f6ger, K., Oertel, M., Friedrichs, B., Lenz, G., and Eich, H.T. (2021). Radiotherapy in Follicular Lymphoma Staged by 18F-FDG-PET\/CT: A German Monocenter Study. Biomedicines, 9.","DOI":"10.3390\/biomedicines9050561"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1016\/j.annonc.2020.11.008","article-title":"Newly Diagnosed and Relapsed Follicular Lymphoma: ESMO Clinical Practice Guidelines for Diagnosis, Treatment and Follow-Up","volume":"32","author":"Dreyling","year":"2021","journal-title":"Ann. Oncol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1007\/s11864-014-0286-4","article-title":"Radiotherapy of Follicular Lymphoma: Updated Role and New Rules","volume":"15","author":"Yahalom","year":"2014","journal-title":"Curr. Treat. Options Oncol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1016\/j.hoc.2005.05.001","article-title":"Unusual Variants of Primary Central Nervous System Lymphoma","volume":"19","author":"Shenkier","year":"2005","journal-title":"Hematol.\/Oncol. Clin. N. Am."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"28897","DOI":"10.18632\/oncotarget.25622","article-title":"Impact of Histologic Subtypes and Treatment Modality among Patients with Primary Central Nervous System Lymphoma: A SEER Database Analysis","volume":"9","author":"Chihara","year":"2018","journal-title":"Oncotarget"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1093\/ajcp\/aqaa032","article-title":"Extranodal Marginal Zone Lymphoma of the Central Nervous System Includes Parenchymal-Based Cases With Characteristic Features","volume":"154","author":"Nomani","year":"2020","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/S0360-3016(00)00470-3","article-title":"Strong Correlation between Imaging Response and Survival among Patients with Primary Central Nervous System Lymphoma: A Secondary Analysis of RTOG Studies 83-15 and 88-06","volume":"47","author":"Corn","year":"2000","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"575","DOI":"10.2176\/nmc.35.575","article-title":"Intracerebral Infiltration by Monoclonal Plasmacytoid Cells in Waldenstrom\u2019\u2019s Macroglobulinemia\u2014Case Report\u2014","volume":"35","author":"Imai","year":"1995","journal-title":"Neurol. Med. Chir."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1159\/000204461","article-title":"Importance of Central Nervous System Involvement by Neoplastic Cells in a Patient with Waldenstr\u00f6m\u2019s Macroglobulinemia Developing Neurologic Abnormalities","volume":"90","author":"Shimizu","year":"1993","journal-title":"Acta Haematol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Daetwyler, E., Bargetzi, M., Otth, M., and Scheinemann, K. (2022). Late Effects of High-Dose Methotrexate Treatment in Childhood Cancer Survivors\u2014A Systematic Review. BMC Cancer, 22.","DOI":"10.1186\/s12885-021-09145-0"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1007\/s11060-019-03279-9","article-title":"White Matter Changes in Primary Central Nervous System Lymphoma Patients Treated with High-Dose Methotrexate with or without Rituximab","volume":"145","author":"Estephan","year":"2019","journal-title":"J. Neurooncol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1212\/WNL.0b013e318297eeba","article-title":"Long-Term Cognitive Function, Neuroimaging, and Quality of Life in Primary CNS Lymphoma","volume":"81","author":"Doolittle","year":"2013","journal-title":"Neurology"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1007\/s00066-019-01541-7","article-title":"De-Escalated Radiotherapy for Indolent Primary Cutaneous B-Cell Lymphoma","volume":"196","author":"Oertel","year":"2020","journal-title":"Strahlenther. Onkol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Rolf, D., Reinartz, G., Rehn, S., Kittel, C., and Eich, H.T. (2022). Development of Organ-Preserving Radiation Therapy in Gastric Marginal Zone Lymphoma. Cancers, 14.","DOI":"10.3390\/cancers14040873"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1016\/S1470-2045(20)30686-0","article-title":"4 Gy versus 24 Gy Radiotherapy for Follicular and Marginal Zone Lymphoma (FoRT): Long-Term Follow-up of a Multicentre, Randomised, Phase 3, Non-Inferiority Trial","volume":"22","author":"Hoskin","year":"2021","journal-title":"Lancet Oncol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Shang, W., Yao, H., Sun, Y., Mu, A., Zhu, L., and Li, X. (2022). Preventive Effect of Hippocampal Sparing on Cognitive Dysfunction of Patients Undergoing Whole-Brain Radiotherapy and Imaging Assessment of Hippocampal Volume Changes. BioMed Res. Int., 2022.","DOI":"10.1155\/2022\/4267673"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Grosu, A.-L., Frings, L., Bentsalo, I., Oehlke, O., Brenner, F., Bilger, A., Fennell, J.T., Rothe, T., Schneider-Fuchs, S., and Graf, E. (2020). Whole-Brain Irradiation with Hippocampal Sparing and Dose Escalation on Metastases: Neurocognitive Testing and Biological Imaging (HIPPORAD)\u2014A Phase II Prospective Randomized Multicenter Trial (NOA-14, ARO 2015\u20133, DKTK-ROG). BMC Cancer, 20.","DOI":"10.1186\/s12885-020-07011-z"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"109663","DOI":"10.1016\/j.radonc.2023.109663","article-title":"ESTRO-EANO Guideline on Target Delineation and Radiotherapy Details for Glioblastoma","volume":"184","author":"Niyazi","year":"2023","journal-title":"Radiother. Oncol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1763","DOI":"10.1212\/01.wnl.0000218284.23872.eb","article-title":"Primary Dural Lymphomas: A Clinicopathologic Study of Treatment and Outcome in Eight Patients","volume":"66","author":"Iwamoto","year":"2006","journal-title":"Neurology"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/15\/23\/5564\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:29:03Z","timestamp":1760131743000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/15\/23\/5564"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,24]]},"references-count":45,"journal-issue":{"issue":"23","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["cancers15235564"],"URL":"https:\/\/doi.org\/10.3390\/cancers15235564","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,24]]}}}