Skip to content
DraconiticResearch
Search Sources API
197,768 studies31 sourcesUpdated 38 min ago
Peer-reviewedCC BY 4.0Acta Neuropathologica

Identification and characterization of a novel distinct Pineal Neoplasm with Neuroendocrine and Epithelial Differentiation (PINNED)

  • Helena Bode1,2,3,4,5
  • Abigail K. Suwala6,7
  • Brian Gudenas8
  • Alicia Fürst1,3,9
  • Neal Geisemeyer6
  • Lea Altendorf1,3
  • Karoline Hack1,3
  • Caterina Giannini10
  • Ziedulla Abdullaev11
  • Sebastian Brandner12
  • Jan Beckervordersandforth13,14
  • Matija Snuderl15
23 more authors
  • Josefine Radke16,17
  • Carlos Rodríguez-Antolín18,19
  • Chiara Villa20,21
  • Catherine Godfraind22
  • Lindsey Lowder23
  • Aaron Mammoser24
  • Tyler J. Kenning25
  • Kay Hertel26
  • Michael Brodhun26,27
  • Rüdiger Gerlach28
  • Christian Mawrin29,30
  • Guntis Karelis30,31
  • Paul Kerbs6,7
  • Isabell Bludau6,7
  • Andreas von Deimling6,7
  • Stefan M. Pfister2,4,5,32
  • Felix Sahm4,6
  • Alexandre Vasiljevic33
  • Christian Thomas34
  • Martin Hasselblatt34
  • Paul Northcott8
  • Marcel Kool4,5,35
  • Ulrich Schüller1,3,9
35 affiliations
  1. 1Research Institute Children’s Cancer Center Hamburg, Martinistraße 52, N63, 20251 Hamburg, Germany
  2. 2Department of Pediatric Hematology and Oncology, Heidelberg University, Heidelberg, Germany
  3. 3Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
  4. 4Hopp Children’s Cancer Center (KiTZ), Heidelberg, Germany
  5. 5Division of Pediatric Neurooncology, German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Germany
  6. 6Department of Neuropathology, Institute of Pathology, Heidelberg University, Heidelberg, Germany
  7. 7Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), German Consortium for Translational Cancer Research (DKTK), Heidelberg, Germany
  8. 8Department of Developmental Neurobiology, St. Jude Children’s Research Hospital, Memphis, TN USA
  9. 9Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
  10. 10Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN USA
  11. 11Laboratory of Pathology Clinical Methylation Unit, Center for Cancer Research, National Cancer Institute, Bethesda, MD USA
  12. 12Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology and Division of Neuropathology, University College London Hospitals NHS Foundation Trust, London, UK
  13. 13GROW-School for Oncology and Reproduction, Maastricht University, Maastricht, the Netherlands
  14. 14Department of Pathology, Maastricht University Medical Center, Maastricht, the Netherlands
  15. 15Department of Pathology, New York University Langone Health, New York, NY USA
  16. 16Institute of Pathology, University Medicine Greifswald, Greifswald, Germany
  17. 17Institute of Molecular Genomics, University Medicine Greifswald, Greifswald, Germany
  18. 18Cancer Epigenetics Laboratory, INGEMM, La Paz University Hospital, Biomarkers and Experimental Therapeutics in Cancer, IdiPAZ, Madrid, Spain
  19. 19Bioinformatics Unit, INGEMM, La Paz University Hospital, Madrid, Spain
  20. 20CNRS UMR8104, INSERM U1016, Institut Cochin, Université Paris Cité, 75014 Paris, France
  21. 21Department of Pathology, Hôpital Lariboisière, Assistance Publique-Hôpitaux de Paris, 75010 Paris, France
  22. 22Neuropathology Unit, University Hospital of Clermont-Ferrand and UMR1071, Clermont Auvergne University, Clermont-Ferrand, France
  23. 23Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA USA
  24. 24Department of Neuroscience and Oncology, Piedmont Brain Tumor Center, Piedmont Atlanta Hospital, Atlanta, GA USA
  25. 25Neurosurgery Department, Piedmont Atlanta Hospital, Atlanta, GA USA
  26. 26Department of Pathology and Neuropathology, Helios Clinic Erfurt, Health and Medical University, Erfurt, Germany
  27. 27Department of Neurosurgery, Helios Clinic Erfurt, Health and Medical University, Erfurt, Germany
  28. 28Department of Neurosurgery, Helios Klinikum, Erfurt, Germany
  29. 29Institute for Neuropathology, Magdeburg, Germany
  30. 30Department of Neurology and Neurosurgery, Rīga Stradiņš University, Riga, 1038 Latvia
  31. 31Research Professor (Tenured Professor) Group in Neuroimmunology in the Department of Biology and Microbiology of the Faculty of Medicine, Rīga Stradiņš University, Riga, 1007 Latvia
  32. 32National Center for Tumor Diseases (NCT), Heidelberg, Germany
  33. 33Department of Pathology and Neuropathology, Groupement Hospitalier Est, Hospices Civils de Lyon, Bron Cedex, France
  34. 34Institute of Neuropathology, University Hospital Münster, Münster, Germany
  35. 35Princess Máxima Center for Pediatric Oncology, Utrecht, Netherlands
Read full textPDFDOICite

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.

Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1007/s00401-026-03111-5.

Related

  1. Case Report: Definitive radiotherapy for intrathyroidal thymic carcinoma with neuroendocrine differentiation
    Jia Du, Jiankai Wang, Jianbing Song +3
    Frontiers in oncologyPeer-reviewedCC BYFull textNeurologyEurope PMCCrossref
  2. Integrative genomic profiling of large-cell neuroendocrine carcinomas reveals distinct subtypes of high-grade neuroendocrine lung tumors
    Julie George, Vonn Walter, Martin Peifer +59
    Nature CommunicationsPeer-reviewedCC BYFull text379 citedGeneral biologyOncologyHAL
  3. Molecular characterization of large cell neuroendocrine carcinoma of the lung by multilayered omics analysis
    Megumi Tateishi, Yoshiki Otsuka, Ryota Matsuoka +17
    Nature CommunicationsPeer-reviewedCC BY-NC-ND 4.0Full textOncologyCrossref
  4. Metastatic prostate cancer with neuroendocrine differentiation and liver metastases: prognosis and response to platinum-based chemotherapy.
    Christian W Schaaf, G von Amsberg, J J Werner +14
    World journal of urologyPeer-reviewedCC BYFull textGeneral medicineEurope PMCPMC
  5. Distinct patterns of insulin-like growth factor binding protein (IGFBP)-2 and IGFBP-3 expression in oxidant exposed lung epithelial cells
    Valerie Besnard, Sophie Corroyer, Germain Trugnan +4
    Biochimica et Biophysica Acta - Molecular Cell ResearchPeer-reviewedLicence not statedFull text45 citedEndocrinology & metabolismHAL

Cite

BibTeXRIS
BibTeX
@article{bode2026identification,
  title = {{Identification and characterization of a novel distinct Pineal Neoplasm with Neuroendocrine and Epithelial Differentiation (PINNED)}},
  author = {Helena Bode and Abigail K. Suwala and Brian Gudenas and Alicia Fürst and Neal Geisemeyer and Lea Altendorf and Karoline Hack and Caterina Giannini and Ziedulla Abdullaev and Sebastian Brandner and Jan Beckervordersandforth and Matija Snuderl and Josefine Radke and Carlos Rodríguez-Antolín and Chiara Villa and Catherine Godfraind and Lindsey Lowder and Aaron Mammoser and Tyler J. Kenning and Kay Hertel and Michael Brodhun and Rüdiger Gerlach and Christian Mawrin and Guntis Karelis and Paul Kerbs and Isabell Bludau and Andreas von Deimling and Stefan M. Pfister and Felix Sahm and Alexandre Vasiljevic and Christian Thomas and Martin Hasselblatt and Paul Northcott and Marcel Kool and Ulrich Schüller},
  journal = {Acta Neuropathologica},
  year = {2026},
  month = oct,
  doi = {10.1007/s00401-026-03111-5},
  url = {https://doi.org/10.1007/s00401-026-03111-5},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Identification and characterization of a novel distinct Pineal Neoplasm with Neuroendocrine and Epithelial Differentiation (PINNED)
AU  - Helena Bode
AU  - Abigail K. Suwala
AU  - Brian Gudenas
AU  - Alicia Fürst
AU  - Neal Geisemeyer
AU  - Lea Altendorf
AU  - Karoline Hack
AU  - Caterina Giannini
AU  - Ziedulla Abdullaev
AU  - Sebastian Brandner
AU  - Jan Beckervordersandforth
AU  - Matija Snuderl
AU  - Josefine Radke
AU  - Carlos Rodríguez-Antolín
AU  - Chiara Villa
AU  - Catherine Godfraind
AU  - Lindsey Lowder
AU  - Aaron Mammoser
AU  - Tyler J. Kenning
AU  - Kay Hertel
AU  - Michael Brodhun
AU  - Rüdiger Gerlach
AU  - Christian Mawrin
AU  - Guntis Karelis
AU  - Paul Kerbs
AU  - Isabell Bludau
AU  - Andreas von Deimling
AU  - Stefan M. Pfister
AU  - Felix Sahm
AU  - Alexandre Vasiljevic
AU  - Christian Thomas
AU  - Martin Hasselblatt
AU  - Paul Northcott
AU  - Marcel Kool
AU  - Ulrich Schüller
PY  - 2026
DA  - 2026/10/26
JO  - Acta Neuropathologica
DO  - 10.1007/s00401-026-03111-5
UR  - https://doi.org/10.1007/s00401-026-03111-5
AB  - 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.  Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1007/s00401-026-03111-5.
SN  - 0001-6322
SN  - 1432-0533
ER  -