Malignant Peripheral Nerve Sheath Tumors (MPNSTs) are rare tumors that often occur in patients with neurofibromatosis 1. Surgical resection represents the mainstay of treatment. Radiation and chemotherapy have a role in selected patients with MPNST. Accurate pathologic diagnosis remains a challenge in many cases of MPNST. There are many recent advances in the understanding of the molecular pathogenesis of MPNST which represent the best opportunities to develop new strategies for management of patients with MPNST.
"Since neurofibromin is a major RAS inactivator and plays a role as a tumor suppressor, the lack of neurofibromin resulting from NF1 mutation causes disruptions in the RAS-mitogen-activated protein kinase (MAPK) and PI3K-AKT-mTOR signaling pathways, which is implicated in the tumorigenesis and tumor progression of PN to MPNST (5). MPNST, also called malignant schwannoma or neurofibrosarcoma, develops in 8–13% of NF1 patients (6), and it represents a major cause of mortality in NF1 patients (7). Thus, the pathogenesis of the malignant transformation of PN to MPNST in NF1 patients has attracted considerable attention (8,9). "
[Show abstract][Hide abstract] ABSTRACT: Neurofibromatosis type 1 (NF1) caused by NF1 gene mutation is a commonly inherited autosomal dominant disorder. Malignant peripheral nerve sheath tumors (MPNSTs), a type of aggressive sarcoma, are a major cause of mortality in NF1 patients. The malignant transformation of benign plexiform neurofibromas (PNs) to MPNSTs is a marked peculiarity in NF1 patients, yet the pathogenesis remains poorly understood. We found that an actin-associated protein transgelin (SM22) was highly expressed in NF1-deficient MPNST tissues compared to NF1-deficient PN tissues using immunohistological staining and primary cultured MPNST cells in western blot analysis. We further found that this transgelin upregulation was caused by increased transcriptional expression of the TAGLN gene encoding transgelin. Comparison of DNA methylation values in the promoter and subpromoter regions of the TAGLN gene in three types of NF1-deficient primary-cultured cells, derived from an NF1 patient's normal phenotype, a benign PN and MPNST tissues, revealed that the TAGLN gene was hypomethylated in the MPNST cells. Next, to determine the functional role of transgelin in MPNST pathogenesis, we manipulated the TAGLN gene expression and investigated the alteration of the RAS-mitogen-activated protein kinase (MAPK) signaling pathway in the normal-phenotypic and malignant tumor cells. The downregulation of TAGLN expression in NF1-deficient MPNST tumor cells through the treatment of the small interfering RNA resulted in a decrease in the RAS activation (GTP-RAS) and the downstream ERK1/2 activation (phosphorylated ERK1/2), while the overexpression of TAGLN in normal-phenotypic NF1-deficient cells caused an increase in RAS and ERK1/2 activation. These results indicate that upregulation of transgelin caused by hypomethylation of the TAGLN gene is closely involved in tumor progression in NF1.
"Our patient had a tumor huge in size compared to those of previous reports with multiple pleural nodules suggesting metastasis at diagnosis, which indicates delayed diagnosis despite her NF1 stigmata. It is well known that MPNST associated with NF1 shows a poor response to chemotherapy or radiotherapy and the prognosis with residual tumor or metastasis is dismal   . Although doxorubicin/ifosfamide-(AI-) based chemotherapy is known to be somewhat effective for adult MPNST and some pediatric cases   , there is no known standard chemotherapy regimen for treatment of MPNST. "
[Show abstract][Hide abstract] ABSTRACT: Malignant peripheral nerve sheath tumor (MPNST) is a rare soft tissue malignancy usually found in patients with neurofibromatosis type 1 (NF1) with a poor outcome. Although MPNST can be found in any part of the body including head and neck or extremities, intrathoracic MPNST with or without NF1 is uncommon, especially in children or adolescents. Reported herein is a case of huge intrathoracic MPNST in a 16-year-old girl with NF1, and a brief review of the literature.
"This effect was not borne out in multivariate analysis, possibly due to the modest sample size. This finding in favor of surgical outcomes is consistent with studies of peripheral MPNST, where complete surgical resection, when possible, remains the mainstay of treatment   . In the current study, gross total resection was associated with improved survival when compared to patients with partial resection or biopsy on Kaplan-Meier estimates. "
[Show abstract][Hide abstract] ABSTRACT: Peripheral nerve sheath tumors are uncommon neoplasms that can affect any area of the body. Spinal lesions, especially those that are malignant, pose difficult management challenges, and data regarding these lesions are limited by the disease rarity. This study provides a population-based analysis using the Surveillance, Epidemiology, and End Results (SEER) database, focusing on patient characteristics and treatments. Surgery is associated with improved survival, whereas radiation therapy is associated with decreased survival in this cohort with malignant peripheral nerve sheath tumor in the spine.
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