Abstract
Background
Tuberous sclerosis complex is a heritable multisystem disorder associated with genes
involved in the formation of a tumor-suppressor complex acting through the Ras homologue
enriched in brain protein to limit activation of the mammalian target of rapamycin
complex I. Mutations in these genes result in enhanced mammalian target of rapamycin
signaling and may cause neurological manifestations including brain tubers, subependymal
nodules, and subependymal giant cell astrocytomas. These astrocytomas are tumors that
arise near the foramen of Monro and may lead to obstructive hydrocephalus. Standard
therapy has been surgical resection. More recently, mammalian target of rapamycin
inhibitor, everolimus, has been approved for treatment after demonstration of efficacy
in prospective clinical trials.
Methods
We report a 15 year-old girl with tuberous sclerosis complex who proceeded to surgical
resection of her subependymal giant cell astrocytoma after 3 months of treatment with
mammalian target of rapamycin inhibition. We compared her subependymal giant cell
astrocytoma tissue specimen with 12 untreated subependymal giant cell astrocytomas
accessed from The Hospital for Sick Children in Toronto, Canada.
Results
This girl's histopathological findings were consistent with subependymal giant cell
astrocytomas with no exposure to mammalian target of rapamycin inhibitors. There were
no major differences identified on immunohistochemistry at targets downstream of mammalian
target of rapamycin complex 1 or in neighboring signaling pathways. The majority of
cells were reactive to glial fibrillary acidic protein, mitogen-activated protein
kinase, phospho-S6, caspase 3 (95% positivity), and NP-1.
Conclusion
In this one individual, rapamycin therapy did not change the histopathological characteristics
of subependymal giant cell astrocytoma. Mammalian target of rapamycin inhibition involves
complex signaling pathways inducing subependymal giant cell astrocytoma shrinkage.
However, its effect is not easily characterized within tumor tissue.
Keywords
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Article info
Publication history
Published online: June 13, 2015
Accepted:
May 28,
2015
Received:
February 27,
2015
Footnotes
Conflicts of interest: None.
Identification
Copyright
© 2015 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
