title: Glioma-like proliferation within tissues excised as tubers in patients with tuberous sclerosis complex.
abstract: We describe diffuse glioma-like infiltrates in excised tubers in five out of forty Tuberous sclerosis complex (TSC) patients undergoing excision of a tuber at our institution within the last 10 years. All patients presented with refractory seizures. Resection specimens from four patients had the pathognomonic histologic features of neuroglial hamartomas (tubers) and in one case there was cortical microdysgenesis lacking cells typical of TSC. All lesions were associated with an infiltrate of atypical, mostly elongate, glioma-like small cells, which were immunoreactive for GFAP in three, and pS6 (a marker for activity of the mTOR pathway), in two cases. MAP-2 and CD34, were negative and MIB-1 (Ki67) immunostains ranged from <1-21%. Array-based comparative genomic hybridization revealed that these proliferative phenomena were associated with 21 different copy number aberrations in comparison with a tuber without atypical infiltrates. Postoperatively (follow-up period ranging from 8 to 34 months) none of the patients have any evidence of a glioma. We report that tubers resected for treatment of seizures are sometimes associated with glioma-like lesions, which are indistinguishable from infiltrating gliomas by morphology and immunohistochemistry. Genomic analysis with SNP arrays revealed copy number changes which may be associated with the pathogenesis of such infiltrates.
authors.affiliation: Department of Pathology, New York University School of Medicine, New York, NY, USA. ingeborg_fischer@yahoo.com
authors.forename: Ingeborg
authors.initials: I
authors.lastname: Fischer
authors.forename: Clare
authors.initials: C
authors.lastname: Cunliffe
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Bollo
authors.forename: Howard L
authors.initials: HL
authors.lastname: Weiner
authors.forename: Orrin
authors.initials: O
authors.lastname: Devinsky
authors.forename: Martha-Eugenia
authors.initials: ME
authors.lastname: Ruiz-Tachiquin
authors.forename: Toni
authors.initials: T
authors.lastname: Venuto
authors.forename: Alexander
authors.initials: A
authors.lastname: Pearlman
authors.forename: Luis
authors.initials: L
authors.lastname: Chiriboga
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Schneider
authors.forename: Harry
authors.initials: H
authors.lastname: Ostrer
authors.forename: Douglas C
authors.initials: DC
authors.lastname: Miller
mesh_terms: D000293:Adolescent; D001921:Brain / Q000473:pathology*; D001932:Brain Neoplasms / Q000150:complications* / Q000235:genetics / Q000473:pathology; D005260:Female; D018628:Gene Dosage; D005910:Glioma / Q000150:complications* / Q000235:genetics / Q000473:pathology; D006222:Hamartoma / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007223:Infant; D008297:Male; D016133:Polymerase Chain Reaction; D014402:Tuberous Sclerosis / Q000150:complications* / Q000235:genetics / Q000473:pathology*