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Molecular characterization of CNS paragangliomas identifies cauda equina paragangliomas as a distinct tumor entity

Paragangliomas/pheochromocytomas are rare neuroendocrine tumors that arise from the adrenal gland or ganglia at various sites throughout the body. They display a remarkable diversity of driver alterations and are associated with germline mutations in up to 40% of the cases. Comprehensive molecular p...

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Main Authors: Schweizer, Leonille (Author) , Thierfelder, Felix (Author) , Thomas, Christian (Author) , Soschinski, Patrick (Author) , Suwala, Abigail Kora (Author) , Stichel, Damian (Author) , Wefers, Annika K. (Author) , Wessels, Lars (Author) , Misch, Martin (Author) , Kim, Hee-yeong (Author) , Jödicke, Ruben (Author) , Teichmann, Daniel (Author) , Kaul, David (Author) , Kahn, Johannes (Author) , Bockmayr, Michael (Author) , Hasselblatt, Martin (Author) , Younsi, Alexander (Author) , Unterberg, Andreas (Author) , Knie, Bettina (Author) , Walter, Jan (Author) , Al Safatli, Diaa (Author) , May, Sven-Axel (Author) , Jödicke, Andreas (Author) , Ntoulias, Georgios (Author) , Moskopp, Dag (Author) , Vajkoczy, Peter (Author) , Heppner, Frank L. (Author) , Capper, David (Author) , Hartmann, Wolfgang (Author) , Hartmann, Christian (Author) , Deimling, Andreas von (Author) , Reuss, David (Author) , Schöler, Anne (Author) , Koch, Arend (Author)
Format: Article (Journal)
Language:English
Published: 14 September 2020
In: Acta neuropathologica
Year: 2020, Volume: 140, Issue: 6, Pages: 893-906
ISSN:1432-0533
DOI:10.1007/s00401-020-02218-7
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1007/s00401-020-02218-7
Verlag, kostenfrei, Volltext: https://link.springer.com/article/10.1007/s00401-020-02218-7
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Author Notes:Leonille Schweizer, Felix Thierfelder, Christian Thomas, Patrick Soschinski, Abigail Suwala, Damian Stichel, Annika K. Wefers, Lars Wessels, Martin Misch, Hee-yeong Kim, Ruben Jödicke, Daniel Teichmann, David Kaul, Johannes Kahn, Michael Bockmayr, Martin Hasselblatt, Alexander Younsi, Andreas Unterberg, Bettina Knie, Jan Walter, Diaa Al Safatli, Sven-Axel May, Andreas Jödicke, Georgios Ntoulias, Dag Moskopp, Peter Vajkoczy, Frank L. Heppner, David Capper, Wolfgang Hartmann, Christian Hartmann, Andreas von Deimling, David E. Reuss, Anne Schöler, Arend Koch
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Summary:Paragangliomas/pheochromocytomas are rare neuroendocrine tumors that arise from the adrenal gland or ganglia at various sites throughout the body. They display a remarkable diversity of driver alterations and are associated with germline mutations in up to 40% of the cases. Comprehensive molecular profiling of abdomino-thoracic paragangliomas revealed four molecularly defined and clinically relevant subtypes. Paragangliomas of the cauda equina region are considered to belong to one of the defined molecular subtypes, but a systematic molecular analysis has not yet been performed. In this study, we analyzed genome-wide DNA methylation profiles of 57 cauda equina paragangliomas and show that these tumors are epigenetically distinct from non-spinal paragangliomas and other tumors. In contrast to paragangliomas of other sites, chromosomal imbalances are widely lacking in cauda equina paragangliomas. Furthermore, RNA and DNA exome sequencing revealed that frequent genetic alterations found in non-spinal paragangliomas—including the prognostically relevant SDH mutations—are absent in cauda equina paragangliomas. Histologically, cauda equina paragangliomas show frequently gangliocytic differentiation and strong immunoreactivity to pan-cytokeratin and cytokeratin 18, which is not common in paragangliomas of other sites. None of our cases had a familial paraganglioma syndrome. Tumors rarely recurred (9%) or presented with multiple lesions within the spinal compartment (7%), but did not metastasize outside the CNS. In summary, we show that cauda equina paragangliomas represent a distinct, sporadic tumor entity defined by a unique clinical and morpho-molecular profile.
Item Description:Gesehen am 29.09.2025
Physical Description:Online Resource
ISSN:1432-0533
DOI:10.1007/s00401-020-02218-7

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