Dataset Information

A case of malignant peripheral nerve sheath tumor of the hypoglossal nerve after stereotactic radiosurgery treatment.

ABSTRACT: Objectives Hypoglossal schwannomas are rare. Surgical resection has been the standard treatment modality. Radiosurgery has been increasingly used for treatment. Radiation-associated secondary malignancy/malignant transformation has not been documented in the literature for the treatment of nonvestibular schwannomas. Setting The patient was a 52-year-old man with an enlarging high cervical/skull base lesion 8.5 years after CyberKnife treatment of a presumed vagal schwannoma. A decision was made for surgical resection, and the tumor was found to originate from the hypoglossal nerve intraoperatively. Final pathology diagnosis was malignant peripheral nerve sheath tumor. Results Patient had a gross total resection. Three months after resection, he received fractionated radiation of 50 Gy in 25 fractions and a boost gamma knife radiosurgery of 10 Gy to the 50% isodose surface. He remained tumor free on repeat magnetic resonance imaging 9 months after the resection. Conclusion Although extremely rare, radiation treatment of nonvestibular schwannomas can potentially cause malignant transformation.

SUBMITTER: Yang T

PROVIDER: S-EPMC4110120 | biostudies-other | 2014 Aug

REPOSITORIES: biostudies-other

ACCESS DATA

Similar Datasets

Project description:BackgroundWe have found that erbB receptor tyrosine kinases drive Ras hyperactivation and growth in NF1-null malignant peripheral nerve sheath tumors (MPNSTs). However, MPNSTs variably express multiple erbB receptors with distinct functional characteristics and it is not clear which of these receptors drive MPNST pathogenesis. Here, we test the hypothesis that altered erbB4 expression promotes MPNST pathogenesis by uniquely activating key cytoplasmic signaling cascades.MethodsErbB4 expression was assessed using immunohistochemistry, immunocytochemistry, immunoblotting and real-time PCR. To define erbB4 functions, we generated mice that develop MPNSTs with floxed Erbb4 alleles (P0-GGFβ3;Trp53+/-;Erbb4flox/flox mice) and ablated Erbb4 in these tumors. MPNST cell proliferation and survival was assessed using 3H-thymidine incorporation, MTT assays, Real-Time Glo and cell count assays. Control and Erbb4-null MPNST cells were orthotopically xenografted in immunodeficient mice and the growth, proliferation (Ki67 labeling), apoptosis (TUNEL labeling) and angiogenesis of these grafts was analyzed. Antibody arrays querying cytoplasmic kinases were used to identify erbB4-responsive kinases. Pharmacologic or genetic inhibition was used to identify erbB4-responsive kinases that drive proliferation.ResultsAberrant erbB4 expression was evident in 25/30 surgically resected human MPNSTs and in MPNSTs from genetically engineered mouse models (P0-GGFβ3 and P0-GGFβ3;Trp53+/- mice); multiple erbB4 splice variants that differ in their ability to activate PI3 kinase and nuclear signaling were present in MPNST-derived cell lines. Erbb4-null MPNST cells demonstrated decreased proliferation and survival and altered morphology relative to non-ablated controls. Orthotopic allografts of Erbb4-null cells were significantly smaller than controls, with reduced proliferation, survival and vascularization. ERBB4 knockdown in human MPNST cells similarly inhibited DNA synthesis and viability. Although we have previously shown that broad-spectrum erbB inhibitors inhibit Ras activation, Erbb4 ablation did not affect Ras activation, suggesting that erbB4 drives neoplasia via non-Ras dependent pathways. An analysis of 43 candidate kinases identified multiple NRG1β-responsive and erbB4-dependent signaling cascades including the PI3K, WNK1, STAT3, STAT5 and phospholipase-Cγ pathways. Although WNK1 inhibition did not alter proliferation, inhibition of STAT3, STAT5 and phospholipase-Cγ markedly reduced proliferation.ConclusionsErbB4 promotes MPNST growth by activating key non-Ras dependent signaling cascades including the STAT3, STAT5 and phospholipase-Cγ pathways. ErbB4 and its effector pathways are thus potentially useful therapeutic targets in MPNSTs.

Dataset Information

A case of malignant peripheral nerve sheath tumor of the hypoglossal nerve after stereotactic radiosurgery treatment.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets