scholarly journals Malignant Peripheral Nerve Sheath Tumors—A Comprehensive Review of Pathophysiology, Diagnosis, and Multidisciplinary Management

Children ◽  
2022 ◽  
Vol 9 (1) ◽  
pp. 38
Author(s):  
Samantha W. E. Knight ◽  
Tristan E. Knight ◽  
Teresa Santiago ◽  
Andrew J. Murphy ◽  
Abdelhafeez H. Abdelhafeez
Keyword(s):  
Peripheral Nerve ◽  
Relevant Literature ◽  
Soft Tissue Sarcomas ◽  
Neurofibromatosis Type ◽  
Comprehensive Review ◽  
Nerve Sheath Tumors ◽  
Peripheral Nerve Sheath Tumors ◽  
Nerve Sheath ◽  
Medical Oncologists

Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive soft tissue sarcomas (STS) with nerve sheath differentiation and a tendency to metastasize. Although occurring at an incidence of 0.001% in the general population, they are relatively common in individuals with neurofibromatosis type 1 (NF1), for whom the lifetime risk approaches 10%. The staging of MPNSTs is complicated and requires close multi-disciplinary collaboration. Their primary management is most often surgical in nature, with non-surgical modalities playing a supportive, necessary role, particularly in metastatic, invasive, or widespread disease. We, therefore, sought to provide a comprehensive review of the relevant literature describing the characteristics of these tumors, their pathophysiology and risk factors, their diagnosis, and their multi-disciplinary treatment. A close partnership between surgical and medical oncologists is therefore necessary. Advances in the molecular characterization of these tumors have also begun to allow the integration of targeted RAS/RAF/MEK/ERK pathway inhibitors into MPNST management.

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 Treatment of malignant peripheral nerve sheath tumors in pediatric NF1 disease

2020 ◽  
Vol 36 (10) ◽  
pp. 2453-2462
Author(s):  
Enrico Martin ◽  
Uta E. Flucke ◽  
J. Henk Coert ◽  
Max M. van Noesel
Keyword(s):  
Peripheral Nerve ◽  
Radiation Effects ◽  
Soft Tissue Sarcomas ◽  
Standard Of Care ◽  
Response Rates ◽  
Neurofibromatosis Type ◽  
Nerve Sheath Tumors ◽  
Peripheral Nerve Sheath Tumors ◽  
Nerve Sheath

Abstract Background Malignant peripheral nerve sheath tumors (MPNSTs) are rare yet highly aggressive soft tissue sarcomas. Children with neurofibromatosis type 1 (NF1) have a 10% lifetime risk for development of MPNST. Prognosis remains poor and survival seems worse for NF1 patients. Methods This narrative review highlights current practices and pitfalls in the management of MPNST in pediatric NF1 patients. Results Preoperative diagnostics can be challenging, but PET scans have shown to be useful tools. More recently, functional MRI holds promise as well. Surgery remains the mainstay treatment for these patients, but careful planning is needed to minimize postoperative morbidity. Functional reconstructions can play a role in improving functional status. Radiotherapy can be administered to enhance local control in selected cases, but care should be taken to minimize radiation effects as well as reduce the risk of secondary malignancies. The exact role of chemotherapy has yet to be determined. Reports on the efficacy of chemotherapy vary as some report lower effects in NF1 populations. Promisingly, survival seems to ameliorate in the last few decades and response rates of chemotherapy may increase in NF1 populations when administering it as part of standard of care. However, in metastasized disease, response rates remain poor. New systemic therapies are therefore desperately warranted and multiple trials are currently investigating the role of drugs. Targeted drugs are nevertheless not yet included in first line treatment. Conclusion Both research and clinical efforts benefit from multidisciplinary approaches with international collaborations in this rare malignancy.

scholarly journals Genetics of human malignant peripheral nerve sheath tumors

2019 ◽  
Vol 2 (Supplement_1) ◽  
pp. i50-i61 ◽  
Author(s):  
Alexander Pemov ◽  
Hua Li ◽  
William Presley ◽  
Margaret R Wallace ◽  
David T Miller
Keyword(s):  
Peripheral Nerve ◽  
Molecular Mechanisms ◽  
Soft Tissue Sarcomas ◽  
Neurofibromatosis Type ◽  
Single Nucleotide Variants ◽  
Regulatory Pathways ◽  
Nerve Sheath Tumors ◽  
Peripheral Nerve Sheath Tumors ◽  
Nerve Sheath ◽  
Specific Order

Abstract Malignant peripheral nerve sheath tumors (MPNSTs) are heterogeneous, highly aggressive tumors with no widely effective treatment other than surgery. Genomic architecture of MPNST is similar to other soft tissue sarcomas, with a relatively modest burden of single nucleotide variants and an elevated frequency of copy-number alterations. Recent advances in genomic studies identified previously unrecognized critical involvement of polycomb repressor complex 2 (PRC2) core components SUZ12 and EED in transition to malignancy. Notably, somatic changes in NF1, CDKN2A/B, and PRC2 are found in most MPNST regardless of their etiology (e.g. neurofibromatosis type 1-associated vs. sporadic vs. radiation-induced), indicating that similar molecular mechanisms impact pathogenesis in these neoplasms. The timing and specific order of genetic or epigenetic changes may, however, explain the typically poorer prognosis of NF1-associated MPNSTs. Studies that reveal genes and regulatory pathways uniquely altered in malignancies are essential to development of targeted tumor therapies. Characterization of MPNST molecular profiles may also contribute to tools for earlier detection, and prediction of prognosis or drug response. Here we review the genetic discoveries and their implications in understanding MPNST biology.

scholarly journals MALIGNANT PERIPHERAL NERVE SHEATH TUMOUR AT GASTROESOPHAGEAL JUNCTIONA RARE CASE

2021 ◽  
pp. 169-171
Author(s):  
Praveen Babu J ◽  
Sankar Subramanian ◽  
Sandhya Sundaram ◽  
Suresh Kumar P ◽  
Chinni Vikram Asokan
Keyword(s):  
Peripheral Nerve ◽  
Gastroesophageal Junction ◽  
Treatment Protocol ◽  
Soft Tissue Sarcomas ◽  
Neurofibromatosis Type ◽  
Postoperative Recovery ◽  
D2 Lymph Node Dissection ◽  
Nerve Sheath Tumors ◽  
Peripheral Nerve Sheath Tumors ◽  
Nerve Sheath

Malignant peripheral nerve sheath tumors (MPNSTs) are very rare and , represents 3 - 10% of all soft tissue sarcomas. Approximately half of all such tumors are diagnosed in patients with neurofibromatosis type 1 (NF1). The extremities are involved most commonly, and the patient's age is usually 20 - 50 years. We herein describe a case of 63 year old lady with gastroesophageal junction MPNST, which was diagnosed histopathologically after surgery. The patient underwent curative esophagogastrectomy with D2 lymph node dissection and Roux-en-Y esophagojejunostomy. The postoperative recovery was uneventful. The ideal adjuvant treatment protocol is yet to be decided due to the relatively limited number of cases of these tumours previously reported.

scholarly journals Surgical management of malignant peripheral nerve sheath tumors

2007 ◽  
Vol 22 (6) ◽  
pp. 1-8 ◽  
Author(s):  
John Gachiani ◽  
Daniel Kim ◽  
Adriane Nelson ◽  
David Kline
Keyword(s):  
Soft Tissue ◽  
Peripheral Nerve ◽  
Surgical Techniques ◽  
Soft Tissue Sarcomas ◽  
Neurofibromatosis Type ◽  
Surgical Removal ◽  
Complete Excision ◽  
Nerve Sheath Tumors ◽  
Peripheral Nerve Sheath Tumors ◽  
Nerve Sheath

Object The aim of this study was to describe the presentation of patients harboring soft tissue sarcomas involving the nerves, most of which were malignant peripheral nerve sheath tumors (MPNSTs), and provide an algorithm for their treatment. Methods The authors retrospectively analyzed data on 43 surgically treated soft tissue sarcomas involving the nerves, 34 (79%) of which were MPNSTs. Tumor classifications are presented, together with patient numbers, locations of MPNSTs, surgical techniques, and adjunctive treatments. Results The 34 MPNSTs were surgically treated during a period of 40 years. Most of these lesions (19 MPNSTs [56%]) were located in the brachial plexus, whereas the rest were located on other major nerves. Neurofibromatosis Type 1–associated tumors (12 lesions) represented 35% of the total number of MPNSTs. Although the main goal of surgery was complete excision, it was successful in only 16 patients (47%). Of the available records, 18 patients (53%) died due to disease progression. Conclusions Malignant peripheral nerve sheath tumors are rare. Surgical removal with margins when possible coupled by adjuvant radiotherapy offers the best chance of survival. The role of chemotherapy is still being defined.

scholarly journals Neoadjuvant Ifosfamide and Epirubicin in the Treatment of Malignant Peripheral Nerve Sheath Tumors

Sarcoma ◽  
2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Angela C. Hirbe ◽  
Pippa F. Cosper ◽  
Sonika Dahiya ◽  
Brian A. Van Tine
Keyword(s):  
Neoadjuvant Chemotherapy ◽  
Peripheral Nerve ◽  
Clinical Benefit ◽  
Metabolic Response ◽  
Neoadjuvant Treatment ◽  
Soft Tissue Sarcomas ◽  
Nerve Sheath Tumors ◽  
Peripheral Nerve Sheath Tumors ◽  
Nerve Sheath ◽  
Response To Chemotherapy

Background and Objectives. Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive soft tissue sarcomas with poor overall survival. Response to chemotherapy has been debated for these tumors. Methods. We performed a retrospective analysis of the patients at our institution with a biopsy-proven diagnosis of MPNST that underwent neoadjuvant chemotherapy prior to surgery. Results. We retrospectively identified five patients who received neoadjuvant chemotherapy with epirubicin and ifosfamide that demonstrated a 30% reduction in tumor growth and a 60% response rate by RECIST criteria. Additionally, a metabolic response was observed in all three patients who received serial PET scans during neoadjuvant treatment. The clinical benefit rate, which includes stable disease, was 100%. Conclusions. Our data suggest that MPNSTs do respond to epirubicin and ifosfamide based chemotherapy and prospective studies are warranted to further define the clinical benefit.

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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