System Maintenance Notice

Please note that maintenance work is scheduled between 4 AM and 5 AM - CET. During this time, you may experience reduced performance. Thanks for your patience.

Publications

Journal Article Epublish

PubMed: 42611353 DOI: 10.1007/s00401-026-03070-x

Sellar region neurocytomas exhibit a CIMP and neuroendocrine-like epigenetic signature distinct from other intra-axial neurocytomas.

Acta Neuropathol 152(1)

Authors: Thomas M Pearce, Patrick J Cimino, Calixto-Hope G Lucas, Daniel F Marker, Scott Kulich, John M Skaugen, Julia K Kofler, Benjamin B Cho, Kyle Kurek, Kyle Conway, Joshua Klonoski, Miguel A Guzman, Sarra M Belakhoua, Sofia Asioli, Naoko Inoshita, Omkar Singh, Zied Abdullaev, Katrin B M Frauenknecht, Arie Perry, Felipe Andreiuolo, Kenneth Aldape, Valérie Rigau, Romain Appay, Emmanuelle Uro-Coste, Melike Pekmezci, Matija Snuderl, Caterina Giannini, Leonille Schweizer, David Capper, Martha Quezado, M Beatriz S Lopes, Drew Pratt

Affiliations

  • Division of Neuropathology, Department of Pathology, University of Pittsburgh School of Medicine, S701 Scaife Hall, 3550 Terrace Street, Pittsburgh, PA, 15261, USA.
  • Brain Tumor Institute, Children's National Hospital, Washington, DC, USA.
  • Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Molecular and Genomic Pathology Laboratory, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
  • Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Department of Pathology, University of Utah, Pediatric Pathology, Primary Children's Hospital, Salt Lake City, UT, USA.
  • Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA.
  • Department of Pathology, Henry Ford Health, Detroit, MI, USA.
  • Departments of Pathology and Neurology, Saint Louis University School of Medicine, St. Louis, MO, USA.
  • Department of Pathology, NYU Langone Health, New York, NY, USA.
  • Department of Biomedical and Neuromotor Sciences (DIBINEM)-Alma Mater Studiorum-University of Bologna, Bologna, Italy.
  • Department of Pathology, Moriyama Memorial Hospital, Tokyo, Japan.
  • Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
  • Institute of Neuropathology, University Medical Center, Johannes Gutenberg University Mainz, Mainz, Germany.
  • Department of Pathology, University of California San Francisco, San Francisco, CA, USA.
  • Department of Pathology, Instituto Estadual Do Cerebro Paulo Niemeyer, Rio de Janeiro, Brazil.
  • Department of Pathology, Estr. dos Tres Rios, Rede D'OrRio de Janeiro, Brazil.
  • D'Or Institute for Research and Education, Rua Diniz Cordeiro, Rio de Janeiro, Brazil.
  • Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
  • Department of Anatomy Pathology, CHU Montpellier, Montpellier, France.
  • Department of Pathology and Neuropathology, Aix-Marseille University, CHU Timone, AP-HM, Marseille, France.
  • Department of Pathology, University Hospital of Toulouse, University Cancer Institute Oncopole, Toulouse, France.
  • Departments of Neuropathology, Edinger Institute, Institute of Neurology, University of Frankfurt am Main, Heidelberg, Germany.
  • Frankfurt Cancer Institute (FCI), Frankfurt am Main, Frankfurt, Germany.
  • German Cancer Consortium (DKTK), Partner Site Frankfurt/Mainz, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Department of Neuropathology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charitéplatz 1, Berlin, Germany.
  • German Consortium for Translational Cancer Research (DKTK), and German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Department of Pathology, University of Virginia, Charlottesville, VA, USA.
  • Division of Neuropathology, Department of Pathology, University of Pittsburgh School of Medicine, S701 Scaife Hall, 3550 Terrace Street, Pittsburgh, PA, 15261, USA.
  • Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.

Abstract

Sellar region neurocytoma (SELN) is a rare neoplasm whose relationship to other neurocytomas within the central nervous system (CNS) has remained unclear. Prior reports have variably classified SELN as a variant of extraventricular neurocytoma (EVN), while immunohistochemical and ultrastructural studies have suggested a hypothalamic origin. Here, we performed unsupervised clustering of DNA methylation data across a large pan-cancer reference set and identified SELN (n = 20) as distinct from other neurocytomas and regional mimics, as well as clustering with neuroendocrine tumors from other organ sites. SELN exhibited a CIMP-like phenotype, TTF1 negativity (0/8), and AVP (vasopressin) promoter hypomethylation, implicating a magnocellular hypothalamic cell of origin. In evaluable cases, a neuronal/neuroendocrine immunophenotype was observed (synaptophysin 8/8, chromogranin A 5/5) with absent pituitary transcription factor expression (PIT1 and TPIT negative 0/4). DNA sequencing (n = 5) and RNA-based fusion profiling (n = 4) did not detect recurrent mutations or gene fusions, respectively. Patients often presented with visual disturbances or headaches and spanned pediatric and older age groups (median 42 years, range 12.5-75), with no sex predilection. Despite locally aggressive imaging features in some cases (cavernous sinus invasion, carotid encasement, hydrocephalus), disease-free survival (n = 13) was comparable to central neurocytoma, with no disease-related deaths during the limited follow-up. Together, these findings support SELN as a molecularly distinct hypermethylated neuroendocrine-like epitype and clinicopathologic entity.

MeSH

Cells, Neoplasms, Pathology, Phenotype, Neurocytoma, Cluster Analysis, Neurology