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

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.

Authors

Institutions

Publication Details

Journal
Acta Neuropathologica
Published
2026-08-18
DOI
https://doi.org/10.1007/s00401-026-03070-x
Primary Topic
Glioma Diagnosis and Treatment
Type
article
Field-Weighted Citation Impact
0.00
Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

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

John M. Skaugen, Benjamin B. Cho, Naoko Inoshita, Sofia Asioli et al.
Acta Neuropathologica
Glioma Diagnosis and Treatment
article

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

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

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.

Acta NeuropathologicaVol. 152(1)
University of North Carolina at Chapel Hill (US), Goethe University Frankfurt (DE), Primary Children's Hospital (US), Children's National (US), Johns Hopkins University (US), Henry Ford Health System (US), University of Pittsburgh (US), German Cancer Research Center (DE), University of California, San Francisco (US), Johannes Gutenberg University Mainz (DE), Aix-Marseille Université (FR), Heidelberg University (DE), University of Michigan (US), Johns Hopkins Medicine (US), Humboldt-Universität zu Berlin (DE), NYU Langone Health (US), Centre Hospitalier Universitaire de Montpellier (FR), University Medical Center of the Johannes Gutenberg University Mainz (DE), Institut universitaire du cancer de Toulouse Oncopole (FR), D’Or Institute for Research and Education (BR), Maruyama Memorial General Hospital (JP), Mayo Clinic in Arizona (US), National Cancer Institute (US), Governo do Estado do Rio de Janeiro (BR), Center for Cancer Research (US), Frankfurt Cancer Institute (DE), Instituto Estadual do Cérebro Paulo Niemeyer (BR), Saint Louis University (US), University of Virginia (US), Freie Universität Berlin (DE), Charité - Universitätsmedizin Berlin (DE), University of Bologna (IT)
Good health and well-being
Openalex Percentile: Top 10%
Glioma Diagnosis and Treatment
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.