scholarly journals Survival and NF1 Analysis in a Cohort of Orthopedics Patients with Malignant Peripheral Nerve Sheath Tumors

Sarcoma ◽  
2021 ◽  
Vol 2021 ◽  
pp. 1-6
Author(s):  
Daniel K. Knewitz ◽  
Colin J. Anderson ◽  
William T. Presley ◽  
MaryBeth Horodyski ◽  
Mark T. Scarborough ◽  
...  
Keyword(s):  
Peripheral Nerve ◽  
Survival Rates ◽  
Treatment Guideline ◽  
Neurofibromatosis Type ◽  
Adjuvant Radiation ◽  
Nerve Sheath Tumors ◽  
Peripheral Nerve Sheath Tumors ◽  
Large Deletions ◽  
Nerve Sheath ◽  
Increased Risk

Neurofibromatosis type 1 (NF1) is an autosomal dominant tumor syndrome in which benign plexiform neurofibromas are at risk of transforming into malignant peripheral nerve sheath tumors (MPNSTs), a very rare soft-tissue sarcoma. The prognosis of patients with MPNSTs is poor, with most studies reporting <50% survival at five years. However, studies evaluating MPNSTs are limited and report heterogeneous results. Because no MPNST-specific evidence-based treatment guideline exists, individual institutional experiences are very informative to the field. The main objective of this study was to investigate and report MPNST prognostic clinical and genetic biomarkers from our institution’s Orthopedics service experience treating 20 cases from 1992 to 2017. Most patients were treated with resection and adjuvant radiation. Extended follow-up, averaging 11.4 years (ranging 1.1 to 25.1), revealed excellent five-year survival rates: 70% for overall and 60% for metastatic disease. An S100 B immunonegative tumor phenotype was associated with a significantly worse outcome than MPNSTs with positive S100 B stain. In addition, NF1 gene mutation analysis was performed on 27 families with NF1 in which at least one affected family member developed MPNSTs. Of the 27 NF1 germline mutations, five were large deletions spanning (or nearly spanning) the gene (18.5%), substantially more than such deletions in NF1 in general, consistent with increased risk of MPNSTs in such cases.

scholarly journals Malignant Peripheral Nerve Sheath Tumors in Children with Neurofibromatosis Type 1

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Apostolos Pourtsidis ◽  
Dimitrios Doganis ◽  
Margarita Baka ◽  
Despina Bouhoutsou ◽  
Maria Varvoutsi ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Peripheral Nerve ◽  
Neurofibromatosis Type 1 ◽  
Soft Tissue Sarcomas ◽  
Neurofibromatosis Type ◽  
Nerve Sheath Tumors ◽  
Peripheral Nerve Sheath Tumors ◽  
Nerve Sheath ◽  
Increased Risk

Purpose. Malignant peripheral nerve sheath tumors (MPNSTs) are rare in children and account for approximately 5–10% of all soft tissue sarcomas in adults. MPNSTs may occur independently but individuals with neurofibromatosis type 1 (NF1) have a significantly increased risk. Our aim is to present patients with MPNST treated in our department.Cases and Results. In this report we present 4 cases of MPNSTs (3 females: 13, 12, and 13 years old and 1 male: 10 years old) arising in patients with NF1. All of them presented with an enlarging mass and pain at diagnosis. Tumor was located in the buttock, the spinal cord, the trunk, and the left leg proximal to the heel. Wide excision of the tumor and radiotherapy were applied to all and adjuvant chemotherapy was given to three of them after the disease was progressed. All four died 32, 18, 10, and 22 months after diagnosis with progressive disease locally and pulmonary metastases in two of them.Conclusions. In conclusion, MPNSTs arising in patients with NF1 are high grade sarcomas with short survival. Individuals with NF1 should be followed closely in order to identify early the development of MPNSTs. Aggressive surgery and complete excision significantly improves disease-free survival. The usefulness of radiation therapy in MPNSTs is not determined although all patients will receive radiation therapy at some stage of the disease. The role of chemotherapy is unclear.

scholarly journals Malignant Peripheral Nerve Sheath Tumors are not a Feature of Neurofibromatosis Type 2 in the Unirradiated Patient

Neurosurgery ◽  
2017 ◽  
Vol 83 (1) ◽  
pp. 38-42 ◽  
Author(s):  
Andrew T King ◽  
Scott A Rutherford ◽  
Charlotte Hammerbeck-Ward ◽  
Simon K Lloyd ◽  
Simon R Freeman ◽  
...  
Keyword(s):  
Peripheral Nerve ◽  
Vestibular Schwannoma ◽  
Neurofibromatosis Type ◽  
Neurofibromatosis Type 2 ◽  
Nerve Sheath Tumors ◽  
Peripheral Nerve Sheath Tumors ◽  
Nerve Sheath ◽  
Increased Risk

Abstract BACKGROUND The published literature suggests that malignant peripheral nerve sheath tumors (MPNST) occur at increased frequency in neurofibromatosis type 2 (NF2). A recent review based on incidence data in North America showed that 1 per 1000 cerebellopontine angle nerve sheath tumors were malignant. OBJECTIVE To determine whether MPNST occurred spontaneously in NF2 by reviewing our NF2 database. METHODS The prospective database consists of 1253 patients with NF2. One thousand and nine are known to be alive at last follow-up. The presence and laterality/pathology of vestibular schwannoma at diagnosis and last follow-up was sought. RESULTS There were no cases of spontaneous MPNST with 2114 proven (n = 1150) and presumed benign (n = 964) vestibular schwannomas found. Two patients had developed MPNST (1 presumed) after having previously undergone stereotactic radiosurgery for a vestibular schwannoma. CONCLUSION In this series, and from the literature, malignant transformation of a vestibular schwannoma was not a feature of NF2 in the unirradiated patient. NF2 patients should not be told that they have an increased risk of malignant change in a vestibular schwannoma unless they undergo radiation treatment. However, very much larger datasets are required before it can be determined whether there is any association between NF2 and MPNST in the unirradiated patient.

scholarly journals New Model Systems and the Development of Targeted Therapies for the Treatment of Neurofibromatosis Type 1-Associated Malignant Peripheral Nerve Sheath Tumors

Genes ◽  
2020 ◽  
Vol 11 (5) ◽  
pp. 477 ◽  
Author(s):  
Kyle B. Williams ◽  
David A. Largaespada
Keyword(s):  
Schwann Cell ◽  
Peripheral Nerve ◽  
Neurofibromatosis Type 1 ◽  
Single Agent ◽  
Neurofibromatosis Type ◽  
Mek Inhibitors ◽  
Nerve Sheath Tumors ◽  
Peripheral Nerve Sheath Tumors ◽  
Nerve Sheath

Neurofibromatosis Type 1 (NF1) is a common genetic disorder and cancer predisposition syndrome (1:3000 births) caused by mutations in the tumor suppressor gene NF1. NF1 encodes neurofibromin, a negative regulator of the Ras signaling pathway. Individuals with NF1 often develop benign tumors of the peripheral nervous system (neurofibromas), originating from the Schwann cell linage, some of which progress further to malignant peripheral nerve sheath tumors (MPNSTs). Treatment options for neurofibromas and MPNSTs are extremely limited, relying largely on surgical resection and cytotoxic chemotherapy. Identification of novel therapeutic targets in both benign neurofibromas and MPNSTs is critical for improved patient outcomes and quality of life. Recent clinical trials conducted in patients with NF1 for the treatment of symptomatic plexiform neurofibromas using inhibitors of the mitogen-activated protein kinase (MEK) have shown very promising results. However, MEK inhibitors do not work in all patients and have significant side effects. In addition, preliminary evidence suggests single agent use of MEK inhibitors for MPNST treatment will fail. Here, we describe the preclinical efforts that led to the identification of MEK inhibitors as promising therapeutics for the treatment of NF1-related neoplasia and possible reasons they lack single agent efficacy in the treatment of MPNSTs. In addition, we describe work to find targets other than MEK for treatment of MPNST. These have come from studies of RAS biochemistry, in vitro drug screening, forward genetic screens for Schwann cell tumors, and synthetic lethal screens in cells with oncogenic RAS gene mutations. Lastly, we discuss new approaches to exploit drug screening and synthetic lethality with NF1 loss of function mutations in human Schwann cells using CRISPR/Cas9 technology.

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