Sellar region neurocytomas exhibit a CIMP and neuroendocrine-like epigenetic signature distinct from other intra-axial neurocytomas
Year: 2026
Type: article
Study design: Observational Study
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.
Source: Acta Neuropathologica
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
Institutions: University of Pittsburgh, Children's National, Johns Hopkins University, Johns Hopkins Medicine, University of North Carolina at Chapel Hill, Primary Children's Hospital, University of Utah, University of Michigan, Henry Ford Health, Henry Ford Hospital, Saint Louis University, NYU Langone Health, University of Bologna, National Cancer Institute, Center for Cancer Research, Johannes Gutenberg University Mainz, University Medical Center of the Johannes Gutenberg University Mainz, University of California, San Francisco, D’Or Institute for Research and Education, Instituto Estadual do Cérebro Paulo Niemeyer, Mayo Clinic, Centre Hospitalier Universitaire de Montpellier, Aix-Marseille Université, Assistance Publique Hôpitaux de Marseille, Hôpital de la Timone, Institut universitaire du cancer de Toulouse Oncopole, Goethe University Frankfurt, German Cancer Research Center, Frankfurt Cancer Institute, Humboldt-Universität zu Berlin, Deutsches Konsortium für Translationale Krebsforschung, Freie Universität Berlin, Charité - Universitätsmedizin Berlin, University of Virginia
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,990
OpenAlex ID: W7203699917