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

Autor: Alexander Younsi, David E. Reuss, Johannes Kahn, David Capper, Anne Schöler, Georgios Ntoulias, Daniel Teichmann, Hee-Yeong Kim, Dag Moskopp, Diaa Al Safatli, Abigail K. Suwala, Jan Walter, Sven-Axel May, Peter Vajkoczy, David Kaul, Bettina Knie, Frank L. Heppner, Wolfgang Hartmann, Andreas Unterberg, Martin Hasselblatt, Leonille Schweizer, Damian Stichel, Felix Thierfelder, Christian Hartmann, Andreas Jödicke, Arend Koch, Martin Misch, Ruben Jödicke, Annika K. Wefers, Patrick Soschinski, Andreas von Deimling, Michael Bockmayr, Lars Wessels, Christian Thomas
Rok vydání: 2020
Předmět:
Male
musculoskeletal diseases
Pathology
medicine.medical_specialty
genetics [Central Nervous System Neoplasms]
genetics [Paraganglioma]
SDHB
diagnosis [Neoplasm Recurrence
Local]
Neuroendocrine tumors
Biology
Cauda equina
Pathology and Forensic Medicine
Central Nervous System Neoplasms
Diagnosis
Differential
Paraganglioma
Head and neck
Cellular and Molecular Neuroscience
Cytokeratin
genetics [Neuroendocrine Tumors]
Germline mutation
pathology [Cauda Equina]
pathology [Neuroendocrine Tumors]
GATA3
medicine
Humans
ddc:610
pathology [Neoplasm Recurrence
Local]
diagnosis [Neuroendocrine Tumors]
Germ-Line Mutation
Exome sequencing
genetics [Germ-Line Mutation]
Original Paper
DNA methylation
Adrenal gland
pathology [Central Nervous System Neoplasms]
Prognosis
medicine.disease
genetics [Neoplasm Recurrence
Local]
pathology [Paraganglioma]
Neuroendocrine Tumors
medicine.anatomical_structure
Female
Neurology (clinical)
Neoplasm Recurrence
Local
600 Technik
Medizin
angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit
Zdroj: Acta neuropathologica 140(6), 893-906 (2020). doi:10.1007/s00401-020-02218-7
Acta Neuropathologica
ISSN: 1432-0533
0001-6322
Popis: 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. Electronic supplementary material The online version of this article (10.1007/s00401-020-02218-7) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE
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