{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T16:04:37Z","timestamp":1781625877096,"version":"3.54.5"},"reference-count":27,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,12,6]],"date-time":"2025-12-06T00:00:00Z","timestamp":1764979200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T00:00:00Z","timestamp":1768953600000},"content-version":"vor","delay-in-days":46,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"57357 Hospital"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Cancer"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Pineal parenchymal body tumors are rare central nervous system tumors with a variety of presentations ranging from well-differentiated low-grade tumors to undifferentiated highly aggressive tumors. Recent molecular classification has described this heterogeneity, particularly among pineoblastomas (PB) and pineal parenchymal tumor of intermediate differentiation (PPTID).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Our study analyzed 49 patients with pineal parenchymal tumors, including PBs (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200939), papillary tumors of the pineal region (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20095), PPTID (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20092), pineocytoma (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20091), and trilateral retinoblastoma (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20092). Descriptive analysis of patients\u2019 characteristics was done in percentages and numbers. Overall survival (OS) and event-free survival (EFS) analysis were evaluated in relation to age and metastatic status for PB cases. Molecular classification was performed using the EPIC methylation array and analyzed by Heidelberg Classifier on 20 cases, of which sixteen were histopathologically diagnosed as PB.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among PBs, univariate analysis showed that age significantly impacted OS and EFS (p-value\u2009=\u20090.003 and 0.021, respectively), while metastatic status only impacted EFS (p-value\u2009=\u20090.032). In Multivariate analysis, only age was of significance on OS (p-value 0.028). The identified methylation groups were PB-miRNA-1 (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200910), PB-RB1 (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20091), retinoblastoma-MYCN activated (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20091), PPTID KBTBD4-altered (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20091), papillary tumor of the pineal region (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20091), medulloblastoma (MB) WNT activated (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20091), MB non-WNT\/SHH (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20091), CNS embryonal tumor with BRD4-LEUTX fusion (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20091) and unclassified N\/A (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20093).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our data identified age as a prognostic factor affecting survival among our PB cohort. We also highlighted the heterogeneity of pineal parenchymal body tumors, necessitating molecular classification for accurate diagnosis and for developing tailored treatment strategies. We demonstrate the feasibility of identifying new entities and MBs within pineal body tumors, thereby supporting the growing evidence that MBs originate in the pineal region.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical trial number<\/jats:title>\n                    <jats:p>Not applicable.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12885-025-15331-1","type":"journal-article","created":{"date-parts":[[2025,12,6]],"date-time":"2025-12-06T06:37:39Z","timestamp":1765003059000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Descriptive and molecular analysis of pineal parenchymal tumors with clinical correlation"],"prefix":"10.1186","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-4957-8172","authenticated-orcid":false,"given":"Hend","family":"Khaled","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7786-063X","authenticated-orcid":false,"given":"Amal","family":"Mosaab","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hala","family":"Taha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amal","family":"Refaat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nada","family":"Ashraf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed Saad","family":"Zaghloul","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"El-Beltagy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olfat","family":"Ahmad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manal","family":"Zamzam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark W.","family":"Kieran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed","family":"El-Hemaly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6465-9881","authenticated-orcid":false,"given":"Shahenda","family":"El-Naggar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alaa","family":"El-Haddad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,12,6]]},"reference":[{"issue":"5 S","key":"15331_CR1","doi-asserted-by":"publisher","first-page":"V1","DOI":"10.1093\/neuonc\/noac202","volume":"24","author":"QT Ostrom","year":"2022","unstructured":"Ostrom QT, Price M, Neff C, Cioffi G, Waite KA, Kruchko C, et al. CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the united States in 2015\u20132019. Neuro Oncol. 2022;24(5 S):V1\u201395. https:\/\/doi.org\/10.1093\/neuonc\/noac202.","journal-title":"Neuro Oncol"},{"key":"15331_CR2","doi-asserted-by":"publisher","first-page":"1231","DOI":"10.1093\/neuonc\/noab106","volume":"23","author":"DN Louis","year":"2021","unstructured":"Louis DN, Perry A, Wesseling P, Brat DJ, Cree IA, Figarella-Branger D, et al. The 2021 WHO classification of tumors of the central nervous system: a summary. Neuro Oncol. 2021;23:1231\u201351. https:\/\/doi.org\/10.1093\/neuonc\/noab106.","journal-title":"Neuro Oncol"},{"key":"15331_CR3","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14153646","author":"G Lombardi","year":"2022","unstructured":"Lombardi G, Poliani PL, Manara R, Berhouma M, Minniti G, Tabouret E, et al. Diagnosis and treatment of pineal region tumors in adults: A EURACAN overview. Cancers. 2022. https:\/\/doi.org\/10.3390\/cancers14153646.","journal-title":"Cancers"},{"key":"15331_CR4","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejcped.2025.100217","author":"S Depani","year":"2025","unstructured":"Depani S, Vasiljevic A, Mynarek M, Dufour C, Pfaff E, Maaz AU, et al. European clinical practice recommendations for the diagnosis and treatment of paediatric pineal tumours. EJC Paediatric Oncology. 2025. https:\/\/doi.org\/10.1016\/j.ejcped.2025.100217.","journal-title":"EJC Paediatric Oncology"},{"key":"15331_CR5","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13071547","author":"G Favero","year":"2021","unstructured":"Favero G, Bonomini F, Rezzani R. Pineal gland tumors: A review. Cancers. 2021. https:\/\/doi.org\/10.3390\/cancers13071547.","journal-title":"Cancers"},{"key":"15331_CR6","doi-asserted-by":"publisher","first-page":"E420","DOI":"10.1093\/neuros\/nyz062","volume":"85","author":"VN Yamaki","year":"2019","unstructured":"Yamaki VN, Solla DJF, Ribeiro RR, Da Silva SA, Teixeira MJ, Figueiredo EG. Papillary tumor of the pineal region: systematic review and analysis of prognostic factors. Clin Neurosurg. 2019;85:E420-9. https:\/\/doi.org\/10.1093\/neuros\/nyz062.","journal-title":"Clin Neurosurg"},{"key":"15331_CR7","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1016\/j.nec.2011.05.006","volume":"22","author":"SJ Han","year":"2011","unstructured":"Han SJ, Clark AJ, Ivan ME, Parsa AT, Perry A. Pathology of pineal parenchymal tumors. Neurosurg Clin N Am. 2011;22:335\u201340. https:\/\/doi.org\/10.1016\/j.nec.2011.05.006.","journal-title":"Neurosurg Clin N Am"},{"key":"15331_CR8","doi-asserted-by":"publisher","first-page":"2273","DOI":"10.1007\/s00381-022-05637-x","volume":"39","author":"A Vasiljevic","year":"2023","unstructured":"Vasiljevic A. Histopathology and molecular pathology of pediatric pineal parenchymal tumors. Childs Nerv Syst. 2023;39:2273\u201384. https:\/\/doi.org\/10.1007\/s00381-022-05637-x.","journal-title":"Childs Nerv Syst"},{"key":"15331_CR9","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1007\/s00401-019-02094-w","volume":"139","author":"C Thomas","year":"2020","unstructured":"Thomas C, Wefers A, Bens S, Nemes K, Agaimy A, Oyen F, et al. Desmoplastic myxoid tumor, SMARCB1-mutant: clinical, histopathological and molecular characterization of a pineal region tumor encountered in adolescents and adults. Acta Neuropathol. 2020;139:277\u201386. https:\/\/doi.org\/10.1007\/s00401-019-02094-w.","journal-title":"Acta Neuropathol"},{"key":"15331_CR10","doi-asserted-by":"publisher","first-page":"771","DOI":"10.1007\/s00401-021-02284-5","volume":"141","author":"APY Liu","year":"2021","unstructured":"Liu APY, Li BK, Pfaff E, Gudenas B, Vasiljevic A, Orr BA, et al. Clinical and molecular heterogeneity of pineal parenchymal tumors: a consensus study. Acta Neuropathol. 2021;141:771\u201385. https:\/\/doi.org\/10.1007\/s00401-021-02284-5.","journal-title":"Acta Neuropathol"},{"key":"15331_CR11","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1007\/s11060-020-03694-3","volume":"152","author":"N Amer","year":"2021","unstructured":"Amer N, Taha H, Hesham D, Al-Shehaby N, Mosaab A, Soudy M, et al. Aggresomes predict poor outcomes and implicate proteostasis in the pathogenesis of pediatric choroid plexus tumors. J Neurooncol. 2021;152:67\u201378. https:\/\/doi.org\/10.1007\/s11060-020-03694-3.","journal-title":"J Neurooncol"},{"key":"15331_CR12","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1038\/nature26000","volume":"555","author":"D Capper","year":"2018","unstructured":"Capper D, Jones DTW, Sill M, Hovestadt V, Schrimpf D, Sturm D, et al. DNA methylation-based classification of central nervous system tumours. Nature. 2018;555:469\u201374. https:\/\/doi.org\/10.1038\/nature26000.","journal-title":"Nature"},{"key":"15331_CR13","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.28252","author":"MS Abdelbaki","year":"2020","unstructured":"Abdelbaki MS, Abu-Arja MH, Davidson TB, Fangusaro JR, Stanek JR, Dunkel IJ, et al. Pineoblastoma in children less than six years of age: The Head Start I, II, and III experience. Pediatr Blood Cancer. 2020. https:\/\/doi.org\/10.1002\/pbc.28252.","journal-title":"Pediatr Blood Cancer"},{"key":"15331_CR14","doi-asserted-by":"publisher","first-page":"3181","DOI":"10.1200\/JCO.2010.34.4341","volume":"30","author":"DM Ashley","year":"2012","unstructured":"Ashley DM, Merchant TE, Strother D, Zhou T, Duffner P, Burger PC, et al. Induction chemotherapy and conformal radiation therapy for very young children with nonmetastatic medulloblastoma: Children\u2019s Oncology Group study P9934. J Clin Oncol. 2012;30:3181\u20136. https:\/\/doi.org\/10.1200\/JCO.2010.34.4341.","journal-title":"J Clin Oncol"},{"key":"15331_CR15","doi-asserted-by":"publisher","first-page":"3388","DOI":"10.1200\/JCO","volume":"36","author":"EI Hwang","year":"2018","unstructured":"Hwang EI, Kool M, Burger PC, Capper D, Chavez L, Brabetz S, et al. JOURNAL OF CLINICAL ONCOLOGY extensive molecular and clinical heterogeneity in patients with histologically diagnosed CNS-PNET treated as a single entity: A report from the children\u2019s oncology group randomized ACNS0332 trial. J Clin Oncol. 2018;36:3388\u201395. https:\/\/doi.org\/10.1200\/JCO.","journal-title":"J Clin Oncol"},{"key":"15331_CR16","doi-asserted-by":"publisher","unstructured":"Dunkel IJ, Piao J, Chantada GL, Banerjee A, Sherif Abouelnaga, Buchsbaum JC, et al. Intensive Multimodality Therapy for Extraocular Retinoblastoma: A Children's Oncology Group Trial (ARET0321). J Clin Oncol. 2022;40(33):3839-3847. https:\/\/doi.org\/10.1200\/JCO.21.02337.","DOI":"10.1200\/JCO.21.02337"},{"key":"15331_CR17","doi-asserted-by":"publisher","first-page":"576","DOI":"10.1093\/neuonc\/now234","volume":"19","author":"M Mynarek","year":"2017","unstructured":"Mynarek M, Pizer B, Dufour C, Van Vuurden D, Garami M, Massimino M, et al. Evaluation of age-dependent treatment strategies for children and young adults with pineoblastoma: analysis of pooled European Society for Paediatric Oncology (SIOP-E) and US Head Start data. Neuro Oncol. 2017;19:576\u201385. https:\/\/doi.org\/10.1093\/neuonc\/now234.","journal-title":"Neuro Oncol"},{"key":"15331_CR18","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(18)30204-3","author":"GW Robinson","year":"2018","unstructured":"Robinson GW, Rudneva VA, Buchhalter I, Billups CA, Waszak SM, Smith KS, et al. Risk-adapted therapy for young children with medulloblastoma (SJYC07): therapeutic and molecular outcomes from a multicentre, phase 2 trial. Lancet Oncol. 2018. https:\/\/doi.org\/10.1016\/S1470-2045(18)30204-3.","journal-title":"Lancet Oncol"},{"key":"15331_CR19","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1007\/s00401-019-02106-9","volume":"139","author":"APY Liu","year":"2020","unstructured":"Liu APY, Gudenas B, Lin T, Orr BA, Klimo P, Kumar R, et al. Risk-adapted therapy and biological heterogeneity in pineoblastoma: integrated clinico-pathological analysis from the prospective, multi-center SJMB03 and SJYC07 trials. Acta Neuropathol. 2020;139:259\u201371. https:\/\/doi.org\/10.1007\/s00401-019-02106-9.","journal-title":"Acta Neuropathol"},{"key":"15331_CR20","doi-asserted-by":"publisher","unstructured":"Wiechmann AF. Melatonin: parallels in pineal gland and retina. Exp Eye Res. 1986;42(6):507-527. https:\/\/doi.org\/10.1016\/0014-4835(86)90042-4.","DOI":"10.1016\/0014-4835(86)90042-4"},{"key":"15331_CR21","doi-asserted-by":"publisher","first-page":"853","DOI":"10.1007\/s00401-023-02638-1","volume":"146","author":"R Rahmanzade","year":"2023","unstructured":"Rahmanzade R, Pfaff E, Banan R, Sievers P, Suwala AK, Hinz F, et al. Genetical and epigenetical profiling identifies two subgroups of pineal parenchymal tumors of intermediate differentiation (PPTID) with distinct molecular, histological and clinical characteristics. Acta Neuropathol. 2023;146:853\u20136. https:\/\/doi.org\/10.1007\/s00401-023-02638-1.","journal-title":"Acta Neuropathol"},{"key":"15331_CR22","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1007\/s00401-020-02208-9","volume":"140","author":"APY Liu","year":"2020","unstructured":"Liu APY, Priesterbach-Ackley LP, Orr BA, Li BK, Gudenas B, Reddingius RE, et al. WNT-activated embryonal tumors of the pineal region: ectopic medulloblastomas or a novel pineoblastoma subgroup? Acta Neuropathol. 2020;140:595\u20137. https:\/\/doi.org\/10.1007\/s00401-020-02208-9.","journal-title":"Acta Neuropathol"},{"key":"15331_CR23","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-023-01556-3","author":"A Tauzi\u00e8de-Espariat","year":"2023","unstructured":"Tauzi\u00e8de-Espariat A, Simbozel M, Liu APY, Robinson GW, Masliah-Planchon J, Sievers P, et al. A sellar presentation of a WNT-activated embryonal tumor: further evidence of an ectopic medulloblastoma. Acta Neuropathol Commun. 2023. https:\/\/doi.org\/10.1186\/s40478-023-01556-3.","journal-title":"Acta Neuropathol Commun"},{"key":"15331_CR24","doi-asserted-by":"publisher","first-page":"157","DOI":"10.21037\/TP.2020.03.03","volume":"9","author":"EM Thompson","year":"2020","unstructured":"Thompson EM, Ashley D, Landi D. Current medulloblastoma subgroup specific clinical trials. Transl Pediatr. 2020;9:157\u201362. https:\/\/doi.org\/10.21037\/TP.2020.03.03.","journal-title":"Transl Pediatr"},{"key":"15331_CR25","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-024-01746-7","author":"F Andreiuolo","year":"2024","unstructured":"Andreiuolo F, Ferrone CK, Rajan S, Perry A, Guney E, Cham E, et al. Molecular and clinicopathologic characteristics of CNS embryonal tumors with BRD4::LEUTX fusion. Acta Neuropathol Commun. 2024. https:\/\/doi.org\/10.1186\/s40478-024-01746-7.","journal-title":"Acta Neuropathol Commun"},{"key":"15331_CR26","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.omto.2021.03.005","volume":"21","author":"H Yang","year":"2021","unstructured":"Yang H, Wei L, Xun Y, Yang A, You H. BRD4: an emerging prospective therapeutic target in glioma. Mol Ther Oncolytics. 2021;21:1\u201314. https:\/\/doi.org\/10.1016\/j.omto.2021.03.005.","journal-title":"Mol Ther Oncolytics"},{"key":"15331_CR27","doi-asserted-by":"publisher","DOI":"10.3390\/cancers16081558","author":"MF Huang","year":"2024","unstructured":"Huang MF, Wang YX, Chou YT, Lee DF. Therapeutic strategies for RB1-deficient cancers: intersecting gene regulation and targeted therapy. Cancers. 2024. https:\/\/doi.org\/10.3390\/cancers16081558.","journal-title":"Cancers"}],"container-title":["BMC Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12885-025-15331-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12885-025-15331-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12885-025-15331-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T15:05:47Z","timestamp":1781622347000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s12885-025-15331-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,6]]},"references-count":27,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["15331"],"URL":"https:\/\/doi.org\/10.1186\/s12885-025-15331-1","relation":{},"ISSN":["1471-2407"],"issn-type":[{"value":"1471-2407","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,6]]},"assertion":[{"value":"8 July 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 November 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 December 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The study protocol adheres to the ethical guidelines of the Declaration of Helsinki. The study protocol was approved for research purposes by the Institutional Review Board of the Children\u2019s Cancer Hospital Egypt 57357 (CCHE-57357), Cairo, Egypt (Serial no.37-2023). Due to the retrospective nature of this study and the use of anonymized patient data, the need for individual informed consent to participate was formally waived.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"100"}}