{
  "abstract": "Pineal region tumors are rare neoplasms that occur in all ages and account for less than 1% of all central nervous system (CNS) tumors in adults but are more frequent in children. Here, we describe a previously unrecognized tumor type of pineal origin characterized by a unique and consistent DNA methylation profile that does not match any known CNS tumor class and is distinct from all currently recognized pineal tumor entities. The presented cohort (n = 27) displayed a balanced sex distribution with a mean patient age of 35 years (range 7–75 years). The histopathological analyses demonstrated a highly cellular tumor showing various degrees of necrosis, mitotic activity, papillary structures, rosettes, epithelioid cytology, or signet-ring cells. The tumors consistently expressed cytokeratin 18, synaptophysin, chromogranin A, and OTX2, whereas CRX expression was absent. Four out of 16 tumors (25%) showed ATRX mutations and/or loss of protein expression as revealed by immunohistochemistry. Single-nucleus RNA sequencing confirmed molecular distinctiveness from other pineal neoplasms but revealed the closest similarities to papillary tumors of the pineal region (PTPR). Projection of the transcriptome data onto the cellular trajectory of the developing murine pineal gland suggests that pinealocyte progenitors are the cellular origins. Taken together, our findings define a novel type of pineal region tumor that we provisionally named ‘Pineal Neoplasm with Neuroendocrine and Epithelial Differentiation’ (PINNED). Recognition of this tumor type appears to be important for the accurate diagnosis of pineal region tumors and may have implications for future tumor classification and treatment strategies.\n\nSupplementary Information: The online version contains supplementary material available at https://doi.org/10.1007/s00401-026-03111-5.",
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  "affiliations": [
    "Research Institute Children’s Cancer Center Hamburg, Martinistraße 52, N63, 20251 Hamburg, Germany",
    "Department of Pediatric Hematology and Oncology, Heidelberg University, Heidelberg, Germany",
    "Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany",
    "Hopp Children’s Cancer Center (KiTZ), Heidelberg, Germany",
    "Division of Pediatric Neurooncology, German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Germany",
    "Department of Neuropathology, Institute of Pathology, Heidelberg University, Heidelberg, Germany",
    "Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), German Consortium for Translational Cancer Research (DKTK), Heidelberg, Germany",
    "Department of Developmental Neurobiology, St. Jude Children’s Research Hospital, Memphis, TN USA",
    "Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany",
    "Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN USA",
    "Laboratory of Pathology Clinical Methylation Unit, Center for Cancer Research, National Cancer Institute, Bethesda, MD USA",
    "Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology and Division of Neuropathology, University College London Hospitals NHS Foundation Trust, London, UK",
    "GROW-School for Oncology and Reproduction, Maastricht University, Maastricht, the Netherlands",
    "Department of Pathology, Maastricht University Medical Center, Maastricht, the Netherlands",
    "Department of Pathology, New York University Langone Health, New York, NY USA",
    "Institute of Pathology, University Medicine Greifswald, Greifswald, Germany",
    "Institute of Molecular Genomics, University Medicine Greifswald, Greifswald, Germany",
    "Cancer Epigenetics Laboratory, INGEMM, La Paz University Hospital, Biomarkers and Experimental Therapeutics in Cancer, IdiPAZ, Madrid, Spain",
    "Bioinformatics Unit, INGEMM, La Paz University Hospital, Madrid, Spain",
    "CNRS UMR8104, INSERM U1016, Institut Cochin, Université Paris Cité, 75014 Paris, France",
    "Department of Pathology, Hôpital Lariboisière, Assistance Publique-Hôpitaux de Paris, 75010 Paris, France",
    "Neuropathology Unit, University Hospital of Clermont-Ferrand and UMR1071, Clermont Auvergne University, Clermont-Ferrand, France",
    "Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA USA",
    "Department of Neuroscience and Oncology, Piedmont Brain Tumor Center, Piedmont Atlanta Hospital, Atlanta, GA USA",
    "Neurosurgery Department, Piedmont Atlanta Hospital, Atlanta, GA USA",
    "Department of Pathology and Neuropathology, Helios Clinic Erfurt, Health and Medical University, Erfurt, Germany",
    "Department of Neurosurgery, Helios Clinic Erfurt, Health and Medical University, Erfurt, Germany",
    "Department of Neurosurgery, Helios Klinikum, Erfurt, Germany",
    "Institute for Neuropathology, Magdeburg, Germany",
    "Department of Neurology and Neurosurgery, Rīga Stradiņš University, Riga, 1038 Latvia",
    "Research Professor (Tenured Professor) Group in Neuroimmunology in the Department of Biology and Microbiology of the Faculty of Medicine, Rīga Stradiņš University, Riga, 1007 Latvia",
    "National Center for Tumor Diseases (NCT), Heidelberg, Germany",
    "Department of Pathology and Neuropathology, Groupement Hospitalier Est, Hospices Civils de Lyon, Bron Cedex, France",
    "Institute of Neuropathology, University Hospital Münster, Münster, Germany",
    "Princess Máxima Center for Pediatric Oncology, Utrecht, Netherlands"
  ],
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  "doi": "10.1007/s00401-026-03111-5",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13710622/",
  "id": "9vqvthe52zstj",
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    "1432-0533"
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  "landing_url": "https://doi.org/10.1007/s00401-026-03111-5",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
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  "native_subjects": [
    [
      "heading",
      "Original Paper"
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      "2716|Glioma Diagnosis and Treatment"
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  "pdf_url": "https://link.springer.com/content/pdf/10.1007/s00401-026-03111-5.pdf",
  "pmcid": "PMC13710622",
  "pmid": "42931941",
  "published": "2026-10-26",
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  "ris": "https://research.draconitic.com/paper/9vqvthe52zstj.ris",
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      "origin": "openalex:2716|Glioma Diagnosis and Treatment",
      "subfield": "human-genetics"
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  "title": "Identification and characterization of a novel distinct Pineal Neoplasm with Neuroendocrine and Epithelial Differentiation (PINNED)",
  "title_text": "Identification and characterization of a novel distinct Pineal Neoplasm with Neuroendocrine and Epithelial Differentiation (PINNED)",
  "type": "peer-reviewed",
  "updated_at": "2026-10-31T12:21:33Z",
  "url": "https://research.draconitic.com/paper/9vqvthe52zstj",
  "venue": "Acta Neuropathologica",
  "versions": []
}