Abstract 21
Category: Clinical Science
At the end of the session, participants will be able to:
- Become aware of the new tumor entity VGLL altered CNS schwannoma (VGLLACS)
- Recognize neuroblastoma- like areas in VGLLACS
- Become aware of additional mutations in this tumors
COI Disclosure:
None to disclose.
Presenter
David Munoz is a neuropathologist working at Saint Michael’s Hospital in Toronto.
David G. Munoz1, Sunit Das2, Ju-Yoon Yoon1, Robert Siddaway3, Adrian Levine3, Kenneth D. Aldape4
1 Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada and Department of Laboratory Medicine, Unity Health Toronto, Toronto, ON, Canada
2Department of Surgery, division of Neurosurgery, Unity Health Toronto, Toronto, ON, Canada
3Department of Laboratory Medicine, Hospital for Sick Children, Toronto, On, Canada
4Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD.
Target Audience:
Pathologists, Residents
CanMEDS:
Medical Expert (the integrating role), Communicator, Collaborator, Scholar, Professional
Additional presence of LZTR1 mutation in a VGLL-fused central nervous system schwannoma with neuroblastoma- like cell dense areas
Abstract
Vestigial-like family (VGLL) altered CNS schwannoma (VGLLACS) is a new tumor entity, recognizable by DNA methylation approaches. The critical alteration is a fusion, involving either VGLL1 or VGLL3. The fusion partner can be EWSR1, CHD7, and rarely SS18. A recent series of 20 VGLLACS did not identify additional recurrent mutations. To add to the span of the condition, we report a previously healthy 29-year-old man who presented with a clonic seizure. Head MRI showed an avidly enhancing well-demarcated intra-axial nodule in the left superior frontal gyrus extending to cortex. At surgery the intra-axial firm mass, well-demarcated from the brain, was completely resected. Histologically, most of the tumor consisted of spindle cells arranged in streams organized in rhythmic palisades in a collagenous background. In addition, there was a peripheral nodule made up of densely packed neuroblastoma- like cells. Both areas showed GFAP expression, and reticulin single cell wrapping. At the periphery the tumor was interspersed with synaptophysin-rich neuropil, and Rosenthal fibers were present within the tumor. A methylation profile analysis carried out at the National Cancer Institute matched to CNS Schwannoma VGLL-fused. TruSight PanCancer next generation sequencing (NGS) revealed a EWSR1::VGLL1 fusion, specifically EWSR1 NM_013986 (exon 9, 331 AA) to VGLL1 NM_016267 (5’ UTR , exon 2). A tier II mutation in LZTR1 (p.Trp265*NM_006767.4:c.794G>A) was identified by hybridization-capture NGS assay. Our case represent another rare case of VGLLACS with neuroblastoma- like areas in association with an additional mutation in LZTR1, a gene mutated in both schwannosis and glioblastoma.