PT  - JOURNAL ARTICLE
AU  - Soni, Neetu
AU  - Ora, Manish
AU  - Szekeres, Denes
AU  - Bathla, Girish
AU  - Desai, Amit
AU  - Gupta, Vivek
AU  - Singhal, Aparna
AU  - Agarwal, Amit
TI  - Mesenchymal Nonmeningothelial Tumors of the CNS: Evolving Molecular Landscape and Implications for Neuroradiologists
AID  - 10.3174/ajnr.A8519
DP  - 2025 May 01
TA  - American Journal of Neuroradiology
PG  - 868--878
VI  - 46
IP  - 5
4099  - http://www.ajnr.org/content/46/5/868.short
4100  - http://www.ajnr.org/content/46/5/868.full
SO  - Am. J. Neuroradiol.2025 May 01; 46
AB  - The World Health Organization Classification of Tumors of the Central Nervous System, 5th edition (WHO CNS5) significantly revised the terminology and diagnostic criteria of “mesenchymal nonmeningothelial” tumors of CNS to better align with the classification of these soft tissue tumors outside the CNS. The CNS chapter only covers the entities with distinct histologic or molecular characteristics that occur exclusively or primarily in the CNS. These tumors usually arise from the meninges and are rarely intraparenchymal in origin, mainly in the supratentorial compartment. These tumors are grouped into 3 main categories: soft tissue, chondro-osseous, and notochordal. Soft tissue tumors, the largest group, are further divided into fibroblastic, vascular, and skeletal muscle subtypes. Notably, a new subcategory for “tumors of uncertain differentiation” has been introduced, encompassing 3 new histomolecular entities: FET::cAMP response element-binding protein (CREB) fusion-positive, Capicua transcriptional receptor (CIC)-rearranged sarcoma, and primary intracranial sarcoma, DICER1-mutant. Emerging entities like dural angioleiomyomas and spindle cell neoplasms with neurotrophic receptor kinase (NTRK) rearrangements have been reviewed, although not introduced in WHO CNS5. Given the often nonspecific histology and immunophenotype of mesenchymal nonmeningothelial tumors of uncertain differentiation, molecular techniques have become indispensable for accurate diagnosis. This review provides a comprehensive overview of primary mesenchymal nonmeningothelial CNS tumors, including their clinical, radiologic, histopathologic, and molecular characteristics and treatment strategies.18F-FCH18F-fluorocholineATF1activating transcription factor-1CCMscerebral cavernous malformationCICCapicua transcriptional receptorCMcavernous malformationCREBcAMP response element-binding proteinDCSDICER1-mutant sarcomaEWSR1Ewing sarcoma RNA-binding proteinFUSfused in sarcomaGFAPGlial Fibrillary Acidic ProteinMAPMitogen-Activated Protein KinaseMPNSTmalignant peripheral nerve sheath tumorNAB2nerve growth factor-inducible protein A binding protein 2NTRKneurotrophic receptor kinaseSFTsolitary fibrous tumorSTAT6signal transducer and activator of transcription 6WHO CNS5World Health Organization Classification of Tumors of the Central Nervous System, 5th edition