Glioma-like proliferation within tissues excised as tubers in patients with tuberous sclerosis complex

Ingeborg Fischer, Clare Cunliffe, Robert J. Bollo, Howard L. Weiner, Orrin Devinsky, Martha Eugenia Ruiz-Tachiquin, Toni Venuto, Alexander Pearlman, Luis Chiriboga, Robert J. Schneider, Harry Ostrer, Douglas C. Miller

Research output: Contribution to journalArticle

3 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)67-77
Number of pages11
JournalActa Neuropathologica
Volume116
Issue number1
DOIs
StatePublished - Jul 2008
Externally publishedYes

Fingerprint

Tuberous Sclerosis
Glioma
Seizures
Comparative Genomic Hybridization
Hamartoma
Single Nucleotide Polymorphism
Immunohistochemistry

Keywords

  • Array
  • Astrocytoma
  • Atypical
  • CD34
  • Comparative genomic hybridization
  • Epilepsy
  • Genetics
  • Glioma
  • Hamartin
  • Infiltrate
  • Isomorphic glioma
  • MAP-2
  • Neuroglial hamartoma
  • Proliferation
  • pS6
  • SNP
  • TSC
  • Tuber
  • Tuberin
  • Tuberous sclerosis

ASJC Scopus subject areas

  • Clinical Neurology
  • Pathology and Forensic Medicine
  • Neuroscience(all)

Cite this

Fischer, I., Cunliffe, C., Bollo, R. J., Weiner, H. L., Devinsky, O., Ruiz-Tachiquin, M. E., ... Miller, D. C. (2008). Glioma-like proliferation within tissues excised as tubers in patients with tuberous sclerosis complex. Acta Neuropathologica, 116(1), 67-77. https://doi.org/10.1007/s00401-008-0391-1

Glioma-like proliferation within tissues excised as tubers in patients with tuberous sclerosis complex. / Fischer, Ingeborg; Cunliffe, Clare; Bollo, Robert J.; Weiner, Howard L.; Devinsky, Orrin; Ruiz-Tachiquin, Martha Eugenia; Venuto, Toni; Pearlman, Alexander; Chiriboga, Luis; Schneider, Robert J.; Ostrer, Harry; Miller, Douglas C.

In: Acta Neuropathologica, Vol. 116, No. 1, 07.2008, p. 67-77.

Research output: Contribution to journalArticle

Fischer, I, Cunliffe, C, Bollo, RJ, Weiner, HL, Devinsky, O, Ruiz-Tachiquin, ME, Venuto, T, Pearlman, A, Chiriboga, L, Schneider, RJ, Ostrer, H & Miller, DC 2008, 'Glioma-like proliferation within tissues excised as tubers in patients with tuberous sclerosis complex', Acta Neuropathologica, vol. 116, no. 1, pp. 67-77. https://doi.org/10.1007/s00401-008-0391-1
Fischer, Ingeborg ; Cunliffe, Clare ; Bollo, Robert J. ; Weiner, Howard L. ; Devinsky, Orrin ; Ruiz-Tachiquin, Martha Eugenia ; Venuto, Toni ; Pearlman, Alexander ; Chiriboga, Luis ; Schneider, Robert J. ; Ostrer, Harry ; Miller, Douglas C. / Glioma-like proliferation within tissues excised as tubers in patients with tuberous sclerosis complex. In: Acta Neuropathologica. 2008 ; Vol. 116, No. 1. pp. 67-77.
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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.",
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AU - Devinsky, Orrin

AU - Ruiz-Tachiquin, Martha Eugenia

AU - Venuto, Toni

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AU - Schneider, Robert J.

AU - Ostrer, Harry

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N2 - 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.

AB - 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.

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