{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T17:51:13Z","timestamp":1784310673389,"version":"3.55.0"},"reference-count":36,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2023,12,5]],"date-time":"2023-12-05T00:00:00Z","timestamp":1701734400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Primary anaplastic-lymphoma-kinase (ALK)-positive large-cell lymphoma of the central nervous system (PCNS ALK-positive ALCL) is a rare entity, with a limited consensus reached regarding its management. While this pathology often presents as solitary lesions, the occurrence of multiple tumors within the brain is not uncommon. The lack of distinctive radiological features poses a diagnostic challenge, leading to delays in initiating targeted therapy. Methods: We conducted a comprehensive literature search, identifying seventeen publications for qualitative analysis. Results: The management options and reported patient outcomes in the literature varied significantly, emphasizing the need for a patient-specific approach. The emergence of ALK-specific inhibitors represents a new frontier in this field, demonstrating promising results. Conclusion: PCNS ALK-positive ALCL necessitates a comprehensive understanding and optimized management strategies. A tailored therapeutic approach, integrating surgical intervention with radiotherapy and chemotherapy, appears pivotal in addressing this pathology. The implementation of a therapeutic protocol is anticipated for further advancement in this field.<\/jats:p>","DOI":"10.3390\/jcm12247516","type":"journal-article","created":{"date-parts":[[2023,12,5]],"date-time":"2023-12-05T08:09:17Z","timestamp":1701763757000},"page":"7516","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Primary Anaplastic-Lymphoma-Kinase-Positive Large-Cell Lymphoma of the Central Nervous System: Comprehensive Review of the Literature"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0912-8484","authenticated-orcid":false,"given":"Antonio","family":"Colamaria","sequence":"first","affiliation":[{"name":"Division of Neurosurgery, Policlinico \u201cRiuniti\u201d, 71122 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4737-067X","authenticated-orcid":false,"given":"Augusto","family":"Leone","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, St\u00e4dtisches Klinikum Karlsruhe, 76133 Karlsruhe, Germany"},{"name":"Faculty of Human Medicine, Charit\u00e9 Universit\u00e4tsmedizin Berlin, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6351-9999","authenticated-orcid":false,"given":"Francesco","family":"Carbone","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, St\u00e4dtisches Klinikum Karlsruhe, 76133 Karlsruhe, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasser Andres","family":"Dallos Laguado","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Surgery, University of Foggia, 71122 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola Pio","family":"Fochi","sequence":"additional","affiliation":[{"name":"Division of Neurosurgery, University of Foggia, 71122 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Sacco","sequence":"additional","affiliation":[{"name":"Division of Neurosurgery, \u201cCasa Sollievo della Sofferenza\u201d, 71013 San Giovanni Rotondo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cinzia","family":"Fesce","sequence":"additional","affiliation":[{"name":"Hematology Unit, University Hospital, 71122 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Sanguedolce","sequence":"additional","affiliation":[{"name":"Pathology Unit, Ospedali Riuniti di Foggia, 71122 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guido","family":"Giordano","sequence":"additional","affiliation":[{"name":"Unit of Medical Oncology and Biomolecular Therapy, Department of Medical and Surgical Sciences, University of Foggia, 71122 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgio","family":"Iaconetta","sequence":"additional","affiliation":[{"name":"Unit of Anatomy, Pathological Histology and Diagnostic Cytology, Department of Diagnostic and Pharma-Ceutical Services, Sandro Pertini Hospital, 00157 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uwe","family":"Spetzger","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, St\u00e4dtisches Klinikum Karlsruhe, 76133 Karlsruhe, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi","family":"Coppola","sequence":"additional","affiliation":[{"name":"Unit of Anatomy, Pathological Histology and Diagnostic Cytology, Department of Diagnostic and Pharma-Ceutical Services, Sandro Pertini Hospital, 00157 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6415-6969","authenticated-orcid":false,"given":"Elena","family":"De Santis","sequence":"additional","affiliation":[{"name":"Department of Anatomical, Histological, Forensic Medicine and Orthopedic sciences, La Sapienza University, 00185 Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Coppola","sequence":"additional","affiliation":[{"name":"Department of Radiological, Oncological and Pathological Sciences, La Sapienza University, 00185 Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4008-9092","authenticated-orcid":false,"given":"Matteo","family":"De Notaris","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of Salerno, 84084 Salerno, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1093\/ajcp\/103.4.496","article-title":"Primary Ki-1 (Anaplastic Large Cell) Lymphoma of the Brain and Spinal Cord","volume":"103","author":"Havlioglu","year":"1995","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"311","DOI":"10.5455\/medarh.2016.70.311-313","article-title":"Primary Central Nervous System Anaplastic Large T-cell Lymphoma","volume":"70","author":"Splavski","year":"2016","journal-title":"Med. Arh."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"943","DOI":"10.4103\/0973-1482.162115","article-title":"A rare case of primary anaplastic large cell lymphoma of the central nervous system","volume":"11","author":"Kuntegowdenahalli","year":"2015","journal-title":"J. Can. Res. Ther."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"978","DOI":"10.1016\/S0046-8177(99)90253-8","article-title":"Primary anaplastic large cell lymphoma of the central nervous system","volume":"30","author":"Abdulkader","year":"1999","journal-title":"Hum. Pathol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1002\/pbc.22752","article-title":"Treatment of primary CNS lymphoma with high-dose methotrexate in immunocompetent pediatric patients: Methotrexate for Pediatric CNS Lymphoma","volume":"55","author":"Shah","year":"2010","journal-title":"Pediatr. Blood Cancer"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"655","DOI":"10.3892\/mco.2013.110","article-title":"Clinical presentation of anaplastic large-cell lymphoma in the central nervous system","volume":"1","author":"Nomura","year":"2013","journal-title":"Mol. Clin. Oncol."},{"key":"ref_7","first-page":"bcr1120103550","article-title":"An unusual case of primary anaplastic large cell central nervous system lymphoma: An 8-year success story","volume":"2011","author":"Vivekanandan","year":"2011","journal-title":"Case Rep."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Weijie, L. (2022). Leukemia, Exon Publications.","DOI":"10.36255\/exon-publications-leukemia"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1097\/00000478-200304000-00008","article-title":"Primary Anaplastic Large Cell Lymphoma of the Central Nervous System: Prognostic Effect of ALK-1 Expression","volume":"27","author":"George","year":"2003","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.hemonc.2014.06.005","article-title":"Anaplastic large cell lymphoma presenting as a cerebellar mass","volume":"7","author":"Geetha","year":"2014","journal-title":"Hematol. Oncol. Stem Cell Ther."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"311","DOI":"10.3171\/2014.6.PEDS1492","article-title":"High-dose methotrexate monotherapy followed by radiation for CD30-positive, anaplastic lymphoma kinase-1\u2014Positive anaplastic large-cell lymphoma in the brain of a child: Case report","volume":"14","author":"Furuya","year":"2014","journal-title":"PED"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1159\/000108799","article-title":"Primary Cerebral ALK-1-Positive Anaplastic Large Cell Lymphoma in a Child","volume":"43","author":"Karikari","year":"2007","journal-title":"Pediatr. Neurosurg."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"673","DOI":"10.7205\/MILMED.172.6.673","article-title":"Central Nervous System Anaplastic Large Cell Lymphoma in an Adult: Successful Treatment with a Combination of Radiation and Chemotherapy","volume":"172","author":"Carmichael","year":"2007","journal-title":"Mil. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"205873842094175","DOI":"10.1177\/2058738420941756","article-title":"Primary central nervous system ALK-positive anaplastic large cell lymphoma with CD56 abnormally expression in a Chinese child: Challenge in diagnostic practice","volume":"34","author":"Liu","year":"2020","journal-title":"Int. J. Immunopathol. Pharmacol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"n71","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 statement: An updated guideline for reporting systematic reviews","volume":"372","author":"Page","year":"2021","journal-title":"BMJ"},{"key":"ref_16","unstructured":"Veritas Health Innovation Covidence (2022, May 05). Systematic Review Software, Melbourne, Australia. Available online: www.covidence.org."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1827","DOI":"10.1093\/annonc\/mdf300","article-title":"Primary brain CD30+ ALK1+ anaplastic large cell lymphoma (\u2018ALKoma\u2019): The first case with a combination of \u2018not common\u2019 variants","volume":"13","author":"Ponzoni","year":"2002","journal-title":"Ann. Oncol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1097\/MPH.0b013e31819146d5","article-title":"Favorable Outcome of Primary CNS Anaplastic Large Cell Lymphoma in an Immunocompetent Patient","volume":"31","author":"Ozkaynak","year":"2009","journal-title":"J. Pediatr. Hematol. Oncol."},{"key":"ref_19","first-page":"326","article-title":"Primary anaplastic large cell lymphoma of central nervous system\u2014A case report","volume":"51","author":"Rupani","year":"2005","journal-title":"J. Postgrad. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1159\/000028731","article-title":"Primary Ki-1-Positive T-Cell Lymphoma of the Brain in a Child","volume":"29","author":"Buxton","year":"1998","journal-title":"Pediatr. Neurosurg."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1001\/archneurol.2010.3","article-title":"Primary Central Nervous System Lymphoma","volume":"67","author":"Gerstner","year":"2010","journal-title":"Arch. Neurol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1080\/02688697.2020.1839630","article-title":"ALK-negative CNS anaplastic large cell lymphoma: Case report and review of literature","volume":"37","author":"Lannon","year":"2023","journal-title":"Br. J. Neurosurg."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Hirano, Y., Miyawaki, S., Tanaka, S., Taoka, K., Hongo, H., Teranishi, Y., Takami, H., Takayanagi, S., Kurokawa, M., and Saito, N. (2021). Clinical Features and Prognostic Factors for Primary Anaplastic Large Cell Lymphoma of the Central Nervous System: A Systematic Review. Cancers, 13.","DOI":"10.3390\/cancers13174358"},{"key":"ref_24","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-Oncology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1023\/A:1008201717089","article-title":"Therapeutic management of primary central nervous system lymphoma in immunocompetent patients: Results of a critical review of the literature","volume":"8","author":"Reni","year":"1997","journal-title":"Ann. Oncol."},{"key":"ref_26","first-page":"2993","article-title":"Prognostic significance of CD56 expression for ALK-positive and ALK-negative anaplastic large-cell lymphoma of T\/null cell phenotype","volume":"96","author":"Suzuki","year":"2000","journal-title":"Blood"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/S0360-3016(98)00564-1","article-title":"Primary central nervous system lymphoma in japan: A nationwide survey","volume":"44","author":"Hayabuchi","year":"1999","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"261","DOI":"10.3171\/jns.2000.92.2.0261","article-title":"Primary intracerebral malignant lymphoma: Report of 248 cases","volume":"92","author":"Bataille","year":"2000","journal-title":"J. Neurosurg."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1519","DOI":"10.1023\/A:1008350207930","article-title":"Vaccaro Primary T-cell lymphoma of central nervous system (PTCLCNS): A case with unusual presentation and review of the literature","volume":"10","author":"Pulsoni","year":"1999","journal-title":"Ann. Oncol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"63","DOI":"10.3747\/co.v17i5.621","article-title":"Primary Central Nervous System T-Cell Lymphoma in Aids Patients: Case Report and Literature Review","volume":"17","author":"Latta","year":"2010","journal-title":"Curr. Oncol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1212\/01.wnl.0000300671.37279.0e","article-title":"Long-term outcome in pcnsl patients treated with high-dose methotrexate and deferred radiation","volume":"70","author":"Gerstner","year":"2008","journal-title":"Neurology"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1093\/ajcp\/aqac046","article-title":"Primary Central Nervous System Anaplastic Large Cell Lymphoma, ALK Positive","volume":"158","author":"Ahrendsen","year":"2022","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"333","DOI":"10.3390\/pediatric15020029","article-title":"Future Perspective for ALK-Positive Anaplastic Large Cell Lymphoma with Initial Central Nervous System (CNS) Involvement: Could Next-Generation ALK Inhibitors Replace Brain Radiotherapy for the Prevention of Further CNS Relapse?","volume":"15","author":"Tanaka","year":"2023","journal-title":"Pediatr. Rep."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2255","DOI":"10.3324\/haematol.2021.280081","article-title":"Profound and sustained response with next-generation ALK inhibitors in patients with relapsed or progressive ALK-positive anaplastic large cell lymphoma with central nervous system involvement","volume":"107","author":"Rigaud","year":"2022","journal-title":"Haematologica"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1111\/bjh.16755","article-title":"Neuro-meningeal relapse in anaplastic large-cell lymphoma: Incidence, risk factors and prognosis\u2014A report from the European intergroup for childhood non-Hodgkin lymphoma","volume":"192","author":"Abbas","year":"2021","journal-title":"Br. J. Haematol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"205","DOI":"10.2741\/s434","article-title":"Prognostic factors in paediatric anaplastic large cell lymphoma role of ALK","volume":"7","author":"Woessmann","year":"2015","journal-title":"Front. Biosci."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/12\/24\/7516\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:33:37Z","timestamp":1760132017000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/12\/24\/7516"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,5]]},"references-count":36,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["jcm12247516"],"URL":"https:\/\/doi.org\/10.3390\/jcm12247516","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,5]]}}}