Neuro-Oncology

Updated 01.16.2024
Released 01.16.2024
Expires For CME 01.16.2027

Mesenchymal non-meningothelial tumors [Brief]

Authors: Pouya Jamshidi MD, Nicolas Kostelecky MD

Editor: Rimas V Lukas MD

Introduction

Key points

	• Mesenchymal non-meningothelial tumors are a diverse group of benign and malignant entities that may affect the central nervous system as primary, secondary, or metastatic lesions.
	• Metastatic disease should always be excluded.
	• Many are defined by key molecular characteristics.
	• They demonstrate a broad range of age at clinical presentation.
	• The presenting symptoms are secondary to mass effect on adjacent structures.

Discussion

Mesenchymal neoplasms are a diverse group of benign and malignant tumors arising predominantly from the soft tissue (eg, muscle, fat, fascia, or fibroblasts). The central and peripheral nervous system may be directly affected by these tumors, in cases of primary tumors arising in the CNS or PNS, or they may be secondarily affected due to mass effect or metastases. To cover the broad spectrum of these tumors would be in excess of this article; instead, the focus will be directed on a subset of tumors as suggested by the latest edition of the WHO Classification of Tumors, Central Nervous System (5th edition) (19). However, caution must be taken to exclude the possibility of a systemic malignancy with secondary effects on the nervous system (05).

Solitary fibrous tumor. Solitary fibrous tumors are among the most frequent entities in the radiographic differential diagnosis of dural-based lesions. A fibroblastic neoplasm is defined by the presence of a NAB2::STAT6 fusion that results from inversion at 12q13 (04). These tumors are known for key histologic features, including spindled to ovoid cells haphazardly arranged in a “patternless pattern” with prominent staghorn-shaped vessels (02). The defining fusion can be interrogated using an immunohistochemical stain for STAT6. These were previously called hemangiopericytoma, but that term has fallen out of favor to maintain consistency with the non-CNS nomenclature.

Solitary fibrous tumors most frequently occur supratentorially as dural-based lesions at the skull base, parasagittal, or subfalcine locations. They may occur in spinal locations as well as in the cerebellopontine angle, pineal region, or sella, though these latter locations are less common (18).

Clinical presentation is based on anatomic site and mass effect on adjacent structures. Histologically, they are graded (CNS WHO grades 1, 2, or 3) based on mitotic activity and the presence of tumor necrosis, with higher-grade solitary fibrous tumors showing more aggressive clinical behavior. These tumors may recur locally or may metastasize throughout the CNS as well as outside the CNS (08; 16).

Hemangiomas and vascular malformations. Hemangiomas and vascular malformations are common vascular lesions of the CNS. Vascular malformations include arteriovenous malformations, cavernous malformations, and capillary telangiectasias. Hemangiomas, as in their visceral counterparts, are lobulated tumors composed of variably sized blood vessels with fibrous septations separating the lobules. They may be intraosseous (24). They are more common in the spinal region (often involving the bones of the vertebral column, preferentially in males, and preferentially thoracic or lumbar), and may cause compressive symptoms. They may occur sporadically or in PIK3CA-related overgrowth spectrum (17).

Arteriovenous malformations are fistulas between arteries and veins with intervening gliotic brain parenchyma. They may arise anywhere in the neuraxis, both intra-axial and extra-axial, and may present with acute hemorrhage. They show no sex or age predilection. Notable molecular features include KRAS or BRAF mutations (10).

In contrast to the arteriovenous malformation, cavernous malformations show cavernous vessels without intervening gliotic brain parenchyma. They favor the supratentorial compartment (30) and clinically tend to present with seizures, though acute hemorrhage is a possible presentation. They may be sporadic or familial (07).

Capillary telangiectasias are focal intraparenchymal aggregates of capillary-sized vessels without reactive changes in the adjacent brain parenchyma. They are more common in the pons and are frequently incidental (30).

Hemangioblastomas. Hemangioblastomas are vascular tumors composed of vacuolated stromal cells and reactive vascular cells. They may occur sporadically or syndromically as part of von Hippel-Lindau disease, and both may show mutations in the VHL gene (20). They typically arise in the cerebellum but may be found throughout the neuraxis, including the spinal cord (most frequently dorsal in location) or cauda equina. They are often well-circumscribed and may have solid and cystic components. Clinical symptoms often occur secondary to mass effect.

Von Hippel-Lindau-associated tumors tend to occur at younger ages than their sporadic counterparts. Correlation with clinical and radiographic findings, as well as family history is key for management (09; 23). When observed in von Hippel-Lindau disease, they may occur in a setting of other neoplasms, including renal cell cancer, pheochromocytomas, retinal angiomas, endolymphatic sac tumors, and pancreatic neuroendocrine tumors.

Rhabdomyosarcomas. Rhabdomyosarcomas are clinically aggressive malignant neoplasms of skeletal muscle differentiation. They arise throughout the neuraxis, are more common in children, and are rare. Clinically, they most often present secondary to local mass effect. They commonly show one of two histologic varieties, embryonal and alveolar. The former is characterized by rhabdomyoblastic cells in a loose myxoid matrix, whereas the latter shows primitive round cells separated by fibrous septae.

Embryonal rhabdomyosarcomas typically show somatic mutations in the RAS pathway (eg, KRAS, NRAS), whereas alveolar rhabdomyosarcomas often have either a PAX3::FOXO1 or PAX7::FOXO1 fusion. The PAX3::FOXO1 suggests a worse prognosis, as does alveolar rhabdomyosarcoma overall (25; 31).

Primary intracranial sarcoma, DICER1-mutant. Primary intracranial sarcoma, DICER1-mutant, may show histologic overlap with rhabdomyosarcomas, but it is molecularly and clinically a distinct entity. This tumor is defined by either a somatic or germline mutation in the DICER1 gene and has a distinct DNA methylation profile. The prognostic information in these cases is limited by small case numbers and an absence of long-term follow-up data. They typically arise supratentorially and present with mass effect (14).

Intracranial mesenchymal tumor, FET::CREB fusion-positive. Intracranial mesenchymal tumors, FET::CREB fusion-positive, are variably aggressive intracranial neoplasms. They are defined by the fusion of a FET RNA-binding protein family gene (eg, EWSR1) and a CREB family of transcription factors (eg, CREB1). They show a diverse morphologic spectrum and require confirmation of a FET::CREB fusion for diagnosis (26).

CIC-rearranged sarcoma. CIC-rearranged sarcoma is composed of small round blue cells arranged in sheets with molecular confirmation of the CIC gene fusion to one of several fusion partners, the most common being NUTM1. They are invariably aggressive and may arise anywhere in the neuraxis with associated mass effect on adjacent structures, which dictates their clinical presentation. They typically arise in adolescents but have been reported in all age groups (27; 29; 01).

Ewing sarcoma. like their systemic counterparts, Ewing sarcomas typically show an EWSR1::FLI1 fusion. They are a prototypic example of a small round blue cell tumor, and CNS primaries typically arise from the meninges. Osseous primaries may show local invasion of the CNS as well. They show a wide range in age of clinical presentation but typically occur in children and young adults (11).

Chordoma. Chordomas are notochordal tumors with a characteristic histopathologic appearance of chords of tumor cells separated by myxoid matrix. The tumor cells are large, clear, and show a vacuolated appearance (physaliphorous). They show positive staining for Brachyury and cytokeratin stains but may lose these in more dedifferentiated varieties (12). Classic anatomic sites include the lumbosacral spine and clivus (22).

Chondrosarcoma. Chondrosarcomas are a family of tumors with cartilaginous differentiation. A large proportion of intracranial chondrosarcomas harbor IDH1 or IDH2 mutations. In contrast to the above-described chordoma, these tumors lack brachyury and cytokeratin expression (21; 13).

Mesenchymal chondrosarcoma. Mesenchymal chondrosarcomas are rare, malignant tumors showing a biphasic histologic finding of well-differentiated cartilage and poorly differentiated small round cells (06; 15). They almost invariably harbor a HEY1::NCOA2 fusion (28). Of note, spinal mesenchymal chondrosarcomas show a low rate of recurrence (03).

References

01: Antonescu CR, Owosho AA, Zhang L, et al. Sarcomas with CIC-rearrangements are a distinct pathologic entity with aggressive outcome: a clinicopathologic and molecular study of 115 cases. Am J Surg Pathol 2017;41(7):941-9. PMID 28346326
02: Carneiro SS, Scheithauer BW, Nascimento AG, Hirose T, Davis DH. Solitary fibrous tumor of the meninges: a lesion distinct from fibrous meningioma: a clinicopathologic and immunohistochemical study. Am J Clin Pathol 1996;106(2):217-24. PMID 8712177
03: Chen CW, Chen IH, Hu MH, et al. Primary intradural extramedullary spinal mesenchymal chondrosarcoma: case report and literature review. BMC Musculoskelet Disord 2019;20(1):408. PMID 31484514
04: Chmielecki J, Crago AM, Rosenberg M, et al. Whole-exome sequencing identifies a recurrent NAB2-STAT6 fusion in solitary fibrous tumors. Nat Genet 2013;45(2):131-2. PMID 23313954
05: Dixit KS, Wolinsky JP, Kumthekar P, Horbinski C, Lukas RV. Sarcoma and the nervous system. Neurological Complications of Systemic Cancer and Antineoplastic Therapy 2022:401-13.
06: Fanburg-Smith JC, Auerbach A, Marwaha JS, et al. Immunoprofile of mesenchymal chondrosarcoma: aberrant desmin and EMA expression, retention of INI1, and negative estrogen receptor in 22 female-predominant central nervous system and musculoskeletal cases. Ann Diagn Pathol 2010;14(1):8-14. PMID 20123451
07: Flemming KD, Lanzino G. Cerebral cavernous malformation: what a practicing clinician should know. Mayo Clin Proc 2020;95(9):2005-20. PMID 32605781
08: Fritchie K, Jensch K, Moskalev EA, et al. The impact of histopathology and NAB2-STAT6 fusion subtype in classification and grading of meningeal solitary fibrous tumor/hemangiopericytoma. Acta Neuropathol 2019;137(2):307-19. PMID 30584643
09: Glasker S, Bender BU, Apel TW, et al. The impact of molecular genetic analysis of the VHL gene in patients with haemangioblastomas of the central nervous system. J Neurol Neurosurg Psychiatry 1999;67(6):758-62. PMID 10567493
10: Goss JA, Huang AY, Smith E, et al. Somatic mutations in intracranial arteriovenous malformations. PLoS One 2019;14(12):e0226852. PMID 31891627
11: Grunewald TG, Cidre-Aranaz F, Surdez D, et al. Ewing sarcoma. Nat Rev Dis Primers 2018;4(1):5. PMID 29977059
12: Hung YP, Diaz-Perez JA, Cote GM, et al. Dedifferentiated Chordoma: clinicopathologic and molecular characteristics with integrative analysis. Am J Surg Pathol 2020;44(9):1213-23. PMID 32427623
13: Kitamura Y, Sasaki H, Yoshida K. Genetic aberrations and molecular biology of skull base chordoma and chondrosarcoma. Brain Tumor Pathol 2017;34(2):78-90. PMID 28432450
14: Koelsche C, Mynarek M, Schrimpf D, et al. Primary intracranial spindle cell sarcomawith rhabdomyosarcoma-like features share a highly distinct methylation profile and DICER1 mutations. Acta Neuropathol 2018;136(2):327-37. PMID 29881993
15: Lin L, Varikatt W, Dexter M, Ng T. Diagnostic pitfall in the diagnosis of mesenchymal chondrosarcoma arising in the central nervous system. Neuropathology 2012;32(1):82-90. PMID 21615516
16: Macagno N, Vogels R, Appay R, et al. Grading of meningeal solitary fibrous tumors/hemangiopericytomas: analysis of the prognostic value of the Marseille Grading System in a cohort of 132 patients. Brain Pathol 2019;29(1):18-27. PMID 29600523
17: Martinez-Lopez A, Blasco-Morente G, Perez-Lopez I, et al. CLOVES syndrome: review of a PIK3CA-related overgrowth spectrum (PROS). Clin Genet 2017;91(1):14-21. PMID 27426476
18: Mena H, Ribas JL, Pezeshkpour GH, Cowan DN, Parisi JE. Hemangiopericytoma of the central nervous system: a review of 94 cases. Hum Pathol 1991;22(1):84-91. PMID 1985083
19: Ng HK. Chapter 8: Mesenchymal, non-meningothelial tumours involving the CNS. In: WHO Classification of Tumours Editorial Board. Central Nervous System Tumours. 5th ed. Lyon (France): International Agency for Research on Cancer, 2021:299-338.
20: Nguyen HS, Doan NB, Gelsomino M, et al. Intracranial hemangioblastoma: a SEER-based analysis 2004-2013. Oncotarget 2018;9(46):28009-15. PMID 29963258
21: Rosenberg AE, Nielsen GP, Keel SB, et al. Chondrosarcoma of the base of the skull: a clinicopathologic study of 200 cases with emphasis on its distinction from chordoma. Am J Surg Pathol 1999;23(11):1370-8. PMID 10555005
22: Sebro R, DeLaney T, Hornicek F, et al. Differences in sex distribution, anatomic location and MR imaging appearance of pediatric compared to adult chordomas. BMC Med Imaging 2016;16(1):53. PMID 27609115
23: Shankar GM, Taylor-Weiner A, Lelic N, et al. Sporadic hemangioblastomas are characterized by cryptic VHL inactivation. Acta Neuropathol Commun 2014;2:167. PMID 25589003
24: Singh U, Kalavakonda C, Venkitachalam S, Patil S, Chinnusamy R. Intraosseous Hemangioma of sella: case report and review of literature. World Neurosurg X 2019;3:100030. PMID 31225522
25: Skapek SX, Ferrari A, Gupta AA, et al. Rhabdomyosarcoma. Nat Rev Dis Primers 2019;5(1):1. PMID 30617281
26: Sloan EA, Chiang J, Villanueva-Meyer JE, et al. Intracranial mesenchymal tumor with FET-CREB fusion-A unifying diagnosis for the spectrum of intracranial myxoid mesenchymal tumors and angiomatoid fibrous histiocytoma-like neoplasms. Brain Pathol 2021;31(4):e12918. PMID 33141488
27: Sturm D, Orr BA, Toprak UH, et al. New brain tumor entities emerge from molecular classification of CNS-PNETs. Cell 2016;164(5):1060-1072. PMID 26919435
28: Wang L, Motoi T, Khanin R, et al. Identification of a novel, recurrent HEY1-NCOA2 fusion in mesenchymal chondrosarcoma based on a genome-wide screen of exon-level expression data. Genes Chromosomes Cancer 2012;51(2):127-39. PMID 22034177
29: Yoshida A, Goto K, Kodaira M, et al. CIC-rearranged sarcomas: a study of 20 cases and comparisons with Ewing sarcomas. Am J Surg Pathol 2016;40(3):313-23. PMID 26685084
30: Zafar A, Fiani B, Hadi H, et al. Cerebral vascular malformations and their imaging modalities. Neurol Sci 2020;41(9):2407-21. PMID 32335778
31: Zheng JJ, Zhang GJ, Huo XL, et al. Treatment strategy and long-term outcomes of primary intracranial rhabdomyosarcoma: a single-institution experience and systematic review. J Neurosurg 2019:1-11. PMID 31518985
32: References especially recommended by the author or editor for general reading.

ICD & OMIM codes

ICD: Solitary fibrous tumour: 8815/1

Cavernous haemangioma: 9121/0

Capillary haemangioma: 9131/0

Arteriovenous malformation: 9123/0

Haemangioblastoma: 9161/1

Embryonal rhabdomyosarcoma: 8910/3

Alveolar rhabdomyosarcoma: 8920/3

Rhabdomyosarcoma, pleomorphic-type: 8901/3

Spindle cell rhabdomyosarcoma: 8912/3

Primary intracranial sarcoma, DICER1-mutant: 9480/3

CIC-rearranged sarcoma: 9367/3

Ewing sarcoma: 9364/3

Chordoma: 9370/3

Chondrosarcoma: 9220/3

Dedifferentiated chondrosarcoma: 9243/3

Mesenchymal chondrosarcoma: 9240/3

Neoplasms of uncertain behaviour of connective or other soft tissue & Solitary fibrous tumour, NOS: 2F7C & XH7E62

Other specified malignant mesenchymal neoplasms & Solitary fibrous tumour, malignant: 2B5Y & XH1HP3

Other specified neoplastic haemangioma: 2E81.0Y
Other specified peripheral arteriovenous malformations: Neoplasms of uncertain behaviour of other specified site & Haemangioblastoma: 2F7Y & XH6810

Rhabdomyosarcoma & Embryonal rhabdomyosarcoma, NOS: 2B55.Z & XH83G1

Rhabdomyosarcoma & Alveolar rhabdomyosarcoma: 2B55.Z & XH7099

Rhabdomyosarcoma, primary site & Pleomorphic rhabdomyosarcoma, NOS: 2B55.Z & XH5SX9

Rhabdomyosarcoma, primary site & Spindle cell rhabdomyosarcoma: 2B55.Z & XH7NM2

Neoplasms of uncertain behaviour of connective or other soft tissue: 2F7C & XH9362

Ewing sarcoma of soft tissue: 2B52.3

Ewing sarcoma of bone and articular cartilage of other specified sites: 2B52.Y

Other specified malignant mesenchymal neoplasms & Chordoma, NOS: 2B5Y & XH9GH0

Other specified malignant mesenchymal neoplasms & Chondroid chordoma: 2B5Y & XH17D8

Other specified malignant mesenchymal neoplasms & Dedifferentiated chordoma: 2B5Y & XH7303

Chondrosarcoma of bone or articular cartilage of other specified sites: 2B50.Y

Chondrosarcoma of bone and articular cartilage of unspecified sites & Atypical cartilaginous tumour / chondrosarcoma, grade 1: 2B50.Z & XH0FY0

Chondrosarcoma of bone and articular cartilage of unspecified sites & Chondrosarcoma, grade 2: B50.Z & XH6LT5

Chondrosarcoma of bone and articular cartilage of unspecified sites & Chondrosarcoma, grade 3: 2B50.Z & XH0Y34

Chondrosarcoma of bone and articular cartilage of unspecified sites & Mesenchymal chondrosarcoma: 2B50.Z & XH8X47

This is an article preview.
Start a Free Account
to access the full version.

Nearly 3,000 illustrations, including video clips of neurologic disorders.
Every article is reviewed by our esteemed Editorial Board for accuracy and currency.
Full spectrum of neurology in 1,200 comprehensive articles.
Listen to MedLink on the go with Audio versions of each article.

Questions or Comment?

MedLink®, LLC

3525 Del Mar Heights Rd, Ste 304
San Diego, CA 92130-2122

Toll Free (U.S. + Canada): 800-452-2400

US Number: +1-619-640-4660

Support: service@medlink.com

Editor: editor@medlink.com

ISSN: 2831-9125

Mesenchymal non-meningothelial tumors …

Mesenchymal non-meningothelial tumors [Brief]

Introduction

Key points

Discussion

References

Contributors

Authors

Editor

ICD & OMIM codes

This is an article preview.
Start a Free Account
to access the full version.

Questions or Comment?

Also in This Category

NF2-related schwannomatosis

Atypical teratoid/rhabdoid tumors

Astrocytoma IDH mutant, WHO grade 2

Neoplastic and infectious aneurysms

Spinal meningioma

Dermoid and epidermoid tumors

Leukemia: neurologic complications

Pediatric-type diffuse high-grade gliomas [Brief]

Mesenchymal non-meningothelial tumors [Brief]

Introduction

Key points

Discussion

References

Contributors

Authors

Editor

ICD & OMIM codes

This is an article preview. Start a Free Account to access the full version.

Questions or Comment?

Also in This Category

NF2-related schwannomatosis

Atypical teratoid/rhabdoid tumors

Astrocytoma IDH mutant, WHO grade 2

Neoplastic and infectious aneurysms

Spinal meningioma

Dermoid and epidermoid tumors

Leukemia: neurologic complications

Pediatric-type diffuse high-grade gliomas [Brief]

This is an article preview.
Start a Free Account
to access the full version.