title: Unique findings of subependymal giant cell astrocytoma within cortical tubers in patients with tuberous sclerosis complex: a histopathological evaluation.
abstract: BACKGROUND
  Tuberous sclerosis is associated with three central nervous system pathologies: cortical/subcortical tubers, subependymal nodules (SENs), and subependymal giant cell astrocytomas (SEGAs). Tubers are associated with epilepsy, which is often medication-resistant and often leads to resective surgery. Recently, mammalian target of rapamycin inhibitors (mTORi) have been shown to be effective reducing seizure burden in some patients with tuberous sclerosis complex (TSC)-related refractory epilepsy. mTORi have also been shown to be an alternative for surgery treating SEGAs. We describe several cases of resected tubers that contained SEGA tissue without an intraventricular SEGA.
  
  
  METHODS
  After institutional review board (IRB) protocol approval, we retrospectively reviewed the surgical-pathological data for all TSC patients who underwent cortical resections for treatment of refractory epilepsy at NYU Langone Medical Center and Tel Aviv Medical Center between 2003 and 2013. Data included demographics, epilepsy type, MRI characteristics, epilepsy outcome, and histopathological staining.
  
  
  RESULTS
  We reviewed cortical resections from 75 patients with complete pathological studies. In three patients, cortical lesions demonstrated histopathological findings consistent with a SEGA within the resected tuber tissue, with no intraventricular SEGA. All lesions were cortically based and none had any intraventricular extension. No patient had been treated before surgery with an mTORi. Two of the three patients remain Engel grade I-II. All lesions stained positive for glial fibrillary acidic protein (GFAP), synaptophysin, and neuronal nuclear antigen (NeuN).
  
  
  CONCLUSIONS
  This is the first description of cortical tubers harboring SEGA tissue. This observation though preliminary may suggest a subgroup of patients with intractable epilepsy in whom mTORi may be considered before surgical intervention.
authors.affiliation: Department of Neurosurgery, OhioHealth, Grant and Riverside Medical Center, 111 S Grant Avenue, Columbus, OH, 43215, USA.
authors.forename: Joel S
authors.initials: JS
authors.lastname: Katz
authors.affiliation: Department of Neurosurgery, Division of Pediatric Neurosurgery, NYU Langone Medical Center, 550 First Avenue, New York, NY, 10016, USA.
authors.forename: Hyman
authors.initials: H
authors.lastname: Frankel
authors.affiliation: Department of Neurosurgery, Division of Pediatric Neurosurgery, NYU Langone Medical Center, 550 First Avenue, New York, NY, 10016, USA.
authors.forename: Tracy
authors.initials: T
authors.lastname: Ma
authors.affiliation: Department of Neurosurgery, Division of Pediatric Neurosurgery, NYU Langone Medical Center, 550 First Avenue, New York, NY, 10016, USA.|Department of Pathology, NYU Langone Medical Center, 550 First Avenue, New York, NY, 10016, USA.
authors.forename: David
authors.initials: D
authors.lastname: Zagzag
authors.affiliation: Department of Pathology, NYU Langone Medical Center, 550 First Avenue, New York, NY, 10016, USA.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Liechty
authors.affiliation: Pediatric Neurology Unit, Edmond and Lily Safra Children's Hospital, Chaim Sheba Medical Center, 52621, Tel Hashomer, Israel.
authors.forename: Bruria Ben
authors.initials: BB
authors.lastname: Zeev
authors.affiliation: Pediatric Neurology Unit, Edmond and Lily Safra Children's Hospital, Chaim Sheba Medical Center, 52621, Tel Hashomer, Israel.
authors.forename: Michal
authors.initials: M
authors.lastname: Tzadok
authors.affiliation: Comprehensive Epilepsy Center, NYU Langone Medical Center, 550 First Avenue, New York, NY, 10016, USA.
authors.forename: Orrin
authors.initials: O
authors.lastname: Devinsky
authors.affiliation: Department of Neurosurgery, Texas Children's Hospital, 6701 Fannin Street, Suite 1230.01, Houston, TX, 77030, USA.
authors.forename: Howard L
authors.initials: HL
authors.lastname: Weiner
authors.affiliation: Department of Pediatric Neurosurgery Dana Children's Hospital, Tel Aviv Medical Center, 6 Weizman Street, 64239, Tel Aviv, Israel. jonaroth@gmail.com.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Roth
mesh_terms: D001254:Astrocytoma / Q000000981:diagnostic imaging / Q000209:etiology* / Q000628:therapy; D001932:Brain Neoplasms / Q000000981:diagnostic imaging / Q000209:etiology* / Q000628:therapy; D002540:Cerebral Cortex / Q000000981:diagnostic imaging* / Q000378:metabolism; D002675:Child, Preschool; D016207:Cytokines / Q000378:metabolism; D004827:Epilepsy / Q000000981:diagnostic imaging / Q000209:etiology; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D007223:Infant; D019394:Ki-67 Antigen / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008297:Male; D019635:Neurosurgical Procedures; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D012189:Retrospective Studies; D015898:Tomography Scanners, X-Ray Computed; D014402:Tuberous Sclerosis / Q000150:complications* / Q000000981:diagnostic imaging / Q000628:therapy
chemical_list: D016207:Cytokines; D005904:Glial Fibrillary Acidic Protein; D019394:Ki-67 Antigen; D010751:Phosphopyruvate Hydratase
keywords: Subependymal giant cell astrocytoma; Tuber; Tuberous sclerosis; mTOR inhibitors