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Malignant peripheral nerve sheath tumours (MPNSTs) are aggressive sarcomas that occur rarely in the cervix. Considering the varied clinical features and the absence of a pathognomonic immunohistochemical marker, it is always challenging to diagnose these tumours. Treatment has not been standardised as yet, but a combination of surgery, radiotherapy and chemotherapy is used to treat MPNSTs of the cervix. Here, we report a case of a woman in her 40s with a 10×7 cm polypoidal lesion in the cervix, diagnosed as an MPNST. She was treated with surgery, ifosfamide-based chemotherapy and external beam radiotherapy before developing pulmonary metastases. She was treated with stereotactic body radiotherapy for the pulmonary metastases, and the patient has been on follow-up since then. We are also summarising the clinicopathological findings, surgical treatment and follow-up of all reported cases of cervical MPNSTs to date., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2025. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Objective: To investigate the clinical features, treatment methods, and prognostic influence factors of patients with malignant peripheral nerve sheath tumor (MPNST)., Methods: A retrospective analysis was conducted on 96 MPNST patients treated between January 1, 2015 and December 31, 2021. There were 46 males and 50 females, aged between 15 and 87 years (mean, 48.2 years). The tumors were located in the trunk in 50 cases, extremities in 39 cases, and head and neck in 7 cases. The maximum tumor diameter was <5 cm in 49 cases, ≥5 cm in 32 cases, with 15 cases missing data. Tumor depth was deep in 77 cases and superficial in 19 cases. The Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC) histological grading was G1 in 9 cases, G2 in 12 cases, and G3 in 34 cases, with 41 cases missing data. There were 37 recurrent MPNST cases, 32 cases with neurofibromatosis type 1 (NF1), and 26 cases in stage Ⅳ. Postoperative adjuvant radiotherapy was administered to 25 patients, perioperative chemotherapy to 45 patients, and anlotinib-targeted therapy to 30 patients. R 0 resection was achieved in 73 cases. Patients were divided into groups based on the presence or absence of NF1, and baseline data between the two groups were compared. Kaplan-Meier curves were generated to assess disease-free survival (DFS) and overall survival (OS) based on various factors (age, gender, presence of NF1, recurrent MPNST, stage Ⅳ MPNST, FNCLCC grade, R 0 resection, tumor location, tumor size, tumor depth, perioperative chemotherapy, postoperative adjuvant radiotherapy, and anlotinib-targeted therapy), and differences between survival curves were analyzed using the Log-Rank test. Multivariate COX proportional hazards regression was used to identify independent prognostic factors for MPNST., Results: Patients with NF1 had a significantly higher proportion of superficial tumors and lower FNCLCC grade compared to those without NF1 ( P <0.05); no significant difference was found for other variables ( P <0.05). Kaplan-Meier analysis showed that recurrent MPNST, stage Ⅳ MPNST, FNCLCC grade, R 0 resection, perioperative chemotherapy, and anlotinib-targeted therapy were factors influencing 1-year DFS ( P <0.05), while stage Ⅳ MPNST, FNCLCC grade, and perioperative chemotherapy were factors affecting 3-year OS ( P <0.05). Multivariate COX proportional hazards regression analysis revealed that recurrent MPNST and high-grade FNCLCC (G3) were independent prognostic factors for 1-year DFS ( P <0.05), while stage Ⅳ MPNST, superficial tumor depth, age over 60 years, postoperative adjuvant radiotherapy, and anlotinib-targeted therapy were independent prognostic factors for 3-year OS ( P <0.05)., Conclusion: MPNST patients with NF1 tend to have more superficial tumors and lower FNCLCC grades. FNCLCC grade, R 0 resection, and adjuvant therapies, including radiotherapy and anlotinib-targeted therapy, are closely associated with MPNST prognosis. Complete surgical resection should be prioritized in clinical management, along with adjuvant treatments such as radiotherapy and targeted therapy of anlotinib to improve patient outcomes.

Introduction: Nerve sheath tumours arise from both the central and peripheral nervous systems. In particular, cases of spinal or paraspinal origins are scarce and poorly covered in the literature. This systematic review aims to summarise the body of evidence regarding spinal nerve sheath tumours and assess its quality, to provide the current knowledge on epidemiology, tumour characteristics, diagnostics, treatment strategies and outcomes., Methods and Analysis: Databases including PubMed, Web of Science and Embase will be searched using keywords such as "spinal", "nerve sheath", "neurofibroma", "schwannoma", "neurinoma" and "neurilemoma". The search will be limited to studies published no earlier than 2000 without language restrictions. Case reports, editorials, letters and reviews will be excluded. Reference lists of identified studies will be searched to find possible additional relevant records. Identified studies will be screened for inclusion, by one reviewer at first and then two independent ones in the next step to increase the external validity. The Rayyan platform will be used for the screening and inclusion process. Data extraction within several predetermined areas of interest will proceed. Subjects of interest include epidemiology, histopathology, radiological diagnostics, surgery, complications, non-surgical treatment alternatives, disease outcomes and predictors of outcome, and recurrence rates. On satisfactory amount of homogenous data, a meta-analysis of key outcomes such as recurrence risk or postoperative neurological improvement will be performed. This systematic review will primarily serve as a reference guide to aid in diagnosis and treatment of patients with spinal schwannomas, while also spotlighting the knowledge gaps in the literature to help guide future research initiatives., Ethics and Dissemination: Ethics approval is not required for the protocol or review as both are based on existing publications. For dissemination, the final manuscript will be submitted to a peer-reviewed journal., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Malignant peripheral sheath tumor (MPNST) is a rare, aggressive form of soft-tissue sarcoma that presents a unique set of diagnostic and treatment challenges and is associated with major unmet treatment medical needs., Objective: The chief aim of this review is to consider the epidemiology, histology, anatomic distribution, pathologic signaling pathways, diagnosis, and management of MPNST, with a focus on potential targeted therapies. A subordinate objective was to establish benchmarks for the antitumor activity of such treatments., Results: MPNST has an incidence of 1:100,000 in the general population and 1:3500 among patients with the inherited condition of neurofibromatosis-1. Spindle-cell sarcomas of neural-crest origin, MPNSTs are frequently situated in the extremities and pelvis/trunk, often at the confluence of large nerve roots and bundles. Highly copy-number aberrant and enriched in chromosome 8, MPNSTs have a complex molecular pathogenesis that likely involves the interplay of multiple signaling pathways, including Ras/AKT/mTOR/MAPK, EGFR, p53, PTEN, and PRC2, as well as factors in the tumor microenvironment. A combination of magnetic resonance imaging (MRI) and positron emission tomography with 18 F-fluorodeoxyglucose (FDG-PET) enables comprehensive assessment of both morphology and metabolism, while MRI- and ultrasound-guided core needle biopsy can confirm histopathology. Although surgery with wide excisional margins is now the chief curative approach to localized disease, MPNST-specific survival has not improved in decades. For advanced and metastatic MPNST, radiation and chemotherapy (chiefly with anthracyclines plus ifosfamide) have somewhat promising but still largely uncertain treatment roles, chiefly in local control, downstaging, and palliation. No single druggable target has emerged, no objective responses have been observed with a number of targeted therapies (cumulative disease control rate in our review = 22.9-34.8%), and combinatorial approaches directed toward multiple signal transduction mechanisms are hallmarks of ongoing clinical trials., Conclusions: Despite advances in our understanding of the genetics and molecular biology of MPNST, further research is warranted to: (1) unravel the complex pathogenesis of this condition; (2) improve diagnostic yield; (3) delineate the appropriate roles of chemotherapy and radiation; and (4) develop a targeted therapy (or combination of such treatments) that is well tolerated and prolongs survival., (© 2024. The Author(s).)

Introduction: Malignant peripheral nerve sheath tumors (MPNST) pose a significant therapeutic challenge due to high recurrence rates after surgical resection and a largely ineffective response to traditional chemotherapy. An alternative treatment strategy is oncolytic viroimmunotherapy, which can elicit a durable and systemic antitumor immune response and is Food and Drug Administration (FDA)-approved for the treatment of melanoma. Unfortunately, only a subset of patients responds completely, underscoring the need to address barriers hindering viroimmunotherapy effectiveness., Methods: Here we investigated the therapeutic utility of targeting key components of the MPNST immunosuppressive microenvironment to enhance viroimmunotherapy's antitumor efficacy in three murine models, one of which showed more immunogenic characteristics than the others., Results: Myelomodulatory therapy with pexidartinib, a small molecule inhibitor of CSF1R tyrosine kinase, and the oncolytic herpes simplex virus T-VEC exhibited the most significant increase in median survival time in the highly immunogenic model. Additionally, targeting myeloid cells with the myelomodulatory therapy trabectedin, a small molecule activator of caspase-8 dependent apoptosis, augmented the survival benefit of T-VEC in a less immunogenic MPNST model. However, tumor regressions or shrinkages were not observed. Depletion experiments confirmed that the enhanced survival benefit relied on a T cell response. Furthermore, flow cytometry analysis following combination viroimmunotherapy revealed decreased M2 macrophages and myeloid-derived suppressor cells and increased tumor-specific gp70+ CD8 T cells within the tumor microenvironment., Discussion: In summary, our findings provide compelling evidence for the potential to leverage viroimmunotherapy with myeloid cell targeting against MPNST and warrant further investigation., Competing Interests: LB was employed by JJP Biologics. MSC has served as a consultant for Jazz Pharmaceuticals, Omeros Pharmaceuticals, Servier Pharmaceuticals, Abbvie and Novartis Pharmaceuticals; Speakers Bureau for Jazz Pharmaceuticals, Amgen, Inc., Sanofi and Sobi; Advisory Board for Astra Zeneca; and research funding from Celularity, Merck, Miltenyi Biotec, Servier, Omeros, Jazz and Janssen. KC holds intellectual property for oncolytic virus C134, which was licensed to Mustang Bio. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Paudel, Hutzen, Miller, Garfinkle, Chen, Wang, Glaspell, Currier, Ringwalt, Boon, Mardis, Cairo, Ratner, Dodd, Cassady and Cripe.)

Most malignant peripheral nerve sheath tumors (MPNSTs) are clinically aggressive high-grade sarcomas, arising in individuals with neurofibromatosis type 1 (NF1) at a significantly elevated estimated lifetime frequency of 8%-13%. In the setting of NF1, MPNSTs arise from malignant transformation of benign plexiform neurofibroma and borderline atypical neurofibromas. Composed of neoplastic cells from the Schwannian lineage, these cancers recur in approximately 50% of individuals, and most patients die within five years of diagnosis, despite surgical resection, radiation, and chemotherapy. Treatment for metastatic disease is limited to cytotoxic chemotherapy and investigational clinical trials. In this article, we review the pathophysiology of this aggressive cancer and current approaches to surveillance and treatment.

This article reviews the pathology and management of peripheral nerve tumours, including a framework for investigation and decision-making. Most tumours are benign, including schwannomas and neurofibromas, but malignant peripheral nerve sheath tumours can occur. The risk of malignant change is remote for schwannomas but higher for neurofibromas, particularly in neurofibromatosis type 1. Magnetic resonance imaging is useful for defining the relationship of a swelling with adjacent nerves but is not definitive for tissue diagnosis. Increasing size, pain and neurological deficit suggest malignant change and TruCut needle biopsy is indicated, although there is a risk of sampling error. Excision biopsy preserving nerve function may be carried out for benign tumours to relieve symptoms. Malignant tumours require a multidisciplinary approach. Complete surgical excision with clear margins is the only curative treatment and may be supplemented with radiotherapy and chemotherapy. However, prognosis remains poor, particularly for patients with neurofibromatosis., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Neurofibromatosis type 1 (NF1) is caused by mutations in the NF1 gene that encodes neurofibromin, a RAS GTPase-activating protein. Inactivating NF1 mutations cause hyperactivation of RAS-mediated signaling, resulting in the development of multiple neoplasms, including malignant peripheral nerve sheath tumors (MPNSTs). MPNSTs are an aggressive tumor and the main cause of mortality in patients with NF1. MPNSTs are difficult to resect and refractory to chemo- and radiotherapy, and no molecular therapies currently exist. Immune checkpoint blockade (ICB) is an approach to treat inoperable, undruggable cancers like MPNST, but successful outcomes require an immune cell-rich tumor microenvironment. While MPNSTs are noninflamed "cold" tumors, here, we converted MPNSTs into T cell-inflamed "hot" tumors by activating stimulator of IFN genes (STING) signaling. Mouse genetic and human xenograft MPNST models treated with a STING agonist plus ICB exhibited growth delay via increased apoptotic cell death. This strategy offers a potential treatment regimen for MPNSTs.

Purpose: Malignant peripheral nerve sheath tumors (MPNSTs) are malignant tumors that arise from peripheral nerves and are the leading cause of mortality in Neurofibromatosis Type 1 (NF1). In this study, we characterized whether transcriptomic signatures of T-cell dysfunction (TCD) and exclusion (TCE) that inversely correlate with response to immune checkpoint blockade (ICB) immunotherapy exist in MPNSTs., Methods: MPNST transcriptomes were pooled from Gene Expression Omnibus (GEO). For each sample, a tumor immune dysfunction and exclusion (TIDE) score, TCD and TCE subscores, and cytotoxic T-cell(CTL) level were calculated. In the TIDE predictive algorithm, tumors are predicted to have an ICB response if they are either immunologically hot (CTL-high) without TCD or immunologically cold (CTL-low) without TCE. TIDE scores greater than zero correspond with ICB nonresponse., Results: 73 MPNST samples met inclusion criteria, including 50 NF1-associated MPNSTs (68.5%). The average TIDE score was + 0.41 (SD = 1.16) with 22 (30.1%) predicted ICB responders. 11 samples were CTL-high (15.1%) with an average TCD score of + 0.99 (SD = 0.63). Among 62 CTL-low tumors, 21 were predicted to have ICB response with an average TCE score of + 0.31(SD = 1.20). Age(p = 0.18), sex(p = 0.41), NF1 diagnosis (p = 0.17), and PRC2 loss(p = 0.29) were not associated with ICB responder status., Conclusions: Transcriptomic analysis of TCD and TCE signatures in MPNST samples reveals that a select subset of patients with MPNSTs may benefit from ICB immunotherapy., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Schwann cell-derived neoplasms known as malignant peripheral nerve sheath tumors (MPNSTs) are the most common malignancy and the leading cause of death in individuals with neurofibromatosis Type 1. Using genome-scale shRNA screens, we have previously found evidence suggesting that lysophosphatidic acid receptors (LPARs) are essential for MPNST proliferation and/or survival. Here, we examine the expression and mutational status of all six LPA receptors in MPNSTs, assess the role that individual LPA receptors play in MPNST physiology and examine their ability to activate key neurofibromin-regulated signaling cascades. We found that human Schwann cells express LPAR1 and LPAR6, while MPNST cells express predominantly LPAR1 and LPAR3. Whole exome sequencing of 16 MPNST cell lines showed no evidence of mutations in any LPAR genes or ENPP2, a gene encoding a major LPA biosynthetic enzyme. Oleoyl-LPA, an LPA variant with an unsaturated side chain, promoted MPNST cell proliferation and migration. LPAR1 knockdown ablated the promigratory effect of LPA, while LPAR3 knockdown decreased proliferation. Inhibition of R-Ras signaling with a doxycycline-inducible dominant negative (DN) R-Ras mutant, which inhibits both R-Ras and R-Ras2, blocked LPA's promigratory effect. In contrast, DN R-Ras did not affect migration induced by neuregulin-1β (NRG1β), suggesting that LPA and NRG1β promote MPNST migration via distinct pathways. LPA-induced migration was also inhibited by Y27632, an inhibitor of the ROCK1/2 kinases that mediate R-Ras effects in MPNSTs. Thus, LPAR1 and aberrantly expressed LPAR3 mediate distinct effects in MPNSTs. These receptors and the signaling pathways that they regulate are potentially useful therapeutic targets in MPNSTs., (© 2022 Wiley Periodicals LLC.)

Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive, invasive cancer that comprise around 10% of all soft tissue sarcomas and develop in about 8-13% of patients with Neurofibromatosis Type 1. They are associated with poor prognosis and are the leading cause of mortality in NF1 patients. MPNSTs can also develop sporadically or following exposure to radiation. There is currently no effective targeted therapy to treat MPNSTs and surgical removal remains the mainstay treatment. Unfortunately, surgery is not always possible due to the size and location of the tumor, thus, a better understanding of MPNST initiation and development is required to design novel therapeutics. Here, we provide an overview of MPNST biology and genetics, discuss findings regarding the developmental origin of MPNST, and summarize the various model systems employed to study MPNST. Finally, we discuss current management strategies for MPNST, as well as recent developments in translating basic research findings into potential therapies., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Malignant triton tumor (MTT) is a rare subtype of malignant peripheral nerve sheath tumor with additional rhabdomyolysis differentiation that shows rapid progression and poor clinical outcomes., Case Report: We report the case of an adult male with a metastatic MTT. Despite extensive counseling, the patient initially refused recommended treatment. Upon disease progression, the patient was admitted to our institution and multiple distant organ metastases were found. The patient underwent an above-knee amputation followed by palliative chemotherapy. The patient died a few months later due to rapid disease progression., Conclusion: To our knowledge, this is the first report of a case of MTT with multiple splenic metastases. We also describe the first finding of a frame-shift mutation in the tuberous sclerosis complex 2 (TSC2) gene in a patient with MTT. Because of limited clinical experience and the lack of clinical trials, the effects of chemotherapy and radiation therapy for MTT remain controversial. However, given the aggressive nature of these tumors and the tendency for early recurrence and metastasis, prompt diagnosis and early surgical treatment are crucial for the best outcomes., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Opinion Statement: Malignant peripheral nerve sheath tumors (MPNSTs) are rare mesenchymal neoplasms that represent a profound therapeutic challenge due to their high proclivity for recurrence and metastasis and relatively poor response to systemic therapy regimens. While our understanding of the pathophysiology of MPNST is growing, including loss of the tumor suppressor gene neurofibromin and subsequent activation of the Ras pathway, targeted therapy to modify the poor prognosis seen in MPNST patients has thus far been without success. Correspondingly, MPNST patients are treated as per soft tissue sarcoma treatment algorithms with anthracycline-based therapy as the front-line therapy of choice for patients with unresectable, locally advanced, or metastatic MPNST. Beyond first-line anthracycline-based therapy, other standard cytotoxic chemotherapy agents used in advanced MPNST include the alkylating agent ifosfamide and the topoisomerase II inhibitor etoposide. Notably, soft tissue sarcoma regimens are used in MPNST despite distinct systemic therapy sensitivity and prognosis. This is particularly notable for neurofibromatosis type 1 (NF1)-associated MPNST, which is associated with poorer response to systemic therapy and prognosis than sporadic MPNST. As such, NF1-associated MPNST is a particular area in need of novel therapeutic strategies. Given the lack of benefit in the targeting of unique aspects of MPNST disease biology thus far, pre-clinical studies to identify novel rational therapies are critical to inform future clinical trials.

Neurofibromatosis type 1, the most common phakomatoses, can present with a host of signs and symptoms, usually involving the skin and the peripheral nervous system. It is characterized by a mutation in the neurofibromatosis type 1 gene on chromosome 17q11.2 that codes for the protein neurofibromin. Neurofibromin acts as a tumor suppressor gene by inhibiting rat sarcoma (Ras) activity and its deficiency leads to increased Ras activity, cellular proliferation and tumor formation. This review was conducted to analyze the various targeted therapies at the genetic and molecular level employed to manage the tumors and other clinical presentations associated with neurofibromatosis type 1. Twenty-eight studies of treatment modalities for the conditions associated with neurofibromatosis and which involved either targeted gene therapy or molecular level therapies, including the latest advances, were included in this review. Mitogen-activated protein kinase kinase inhibition, mammalian target of Rapamycin inhibition and Tyrosine kinase inhibition, represent some of the newer treatment options in this category. Although there are a number of trials for providing therapeutic options at the genetic and molecular level for the various physical and psychological morbidities associated with neurofibromatosis type 1, most of them are in the preclinical stage. Increased clinical trials of the molecules and gene therapies could significantly help in managing the various chronic and sometimes, life-threatening conditions associated with neurofibromatosis 1 and these will probably represent the preferred treatment direction of the future.

Background and Objectives: Malignant peripheral nerve sheath tumors (MPNST) are aggressive soft tissue sarcomas that present as large, invasive tumors. Our aim was to assess outcomes, identify prognostic factors, and analyze treatment strategies in a prospectively collected pediatric cohort., Methods: Patients less than 21 years with MPNST treated in the consecutive prospective European Cooperative Weichteilsarkom Studiengruppe (CWS)-trials (1981-2009) and the CWS-SoTiSaR registry (2009-2015) were analyzed., Results: A total of 159 patients were analyzed. Neurofibromatosis type I (NF1) was reported in thirty-eight patients (24%). Most were adolescents (67%) with large (>10 cm, 65%) tumors located at extremities (42%). Nodal involvement was documented in 15 (9%) and distant metastases in 15 (9%) upon diagnosis. Overall, event-free survival (EFS) was 40.5% at 5 and 36.3% at 10 years, and overall survival (OS) was 54.6% at 5 and 47.1% at 10 years. Age, NF1 status, tumor site, tumor size, Intergroup Rhabdomyosarcoma Study (IRS) group, metastatic disease, and achieving first complete remission (CR1) were identified as prognostic factors for EFS and/or OS in the univariate analysis., Conclusions: Prognostic factors were identified and research questions for future clinical trials were addressed., (© 2020 Wiley Periodicals LLC.)

Background: We sought to analyze the clinical data and imaging features from a rare case presenting an intravertebral mobile nerve sheath tumor of the lumbar spine, review the relevant literature, discuss the imaging features and possible causes of the tumor, and propose preventive measures and solutions., Case Description: The clinical data and imaging data of a patient with a lumbar spinal canal mobile nerve sheath tumor were retrospectively analyzed in conjunction with the relevant literature. The first preoperative lumbar spine magnetic resonance imaging (MRI) showed the tumor located at level L1-2. Further lumbar spine MRI, which was performed 5 days later, showed the tumor was at level L3-4, with a range of motion of 8 cm. End spinal resection of the tumor was performed under general anesthesia, and a tumor, which was cystic solid, was found to be located at level L3-4. The tumor originated from a distinctly twisted and elongated posterior root of the spinal cord, with complete fusion of the tumor-bearing nerve. Both the tumor and tumor-carrying nerve were removed. Postoperative pathologic examination confirmed that the tumor was a nerve sheath tumor. Lumbar MRI on postoperative day 10 showed complete resection of the tumor in the L3-4 spinal canal. The patient was discharged with normal urination and defecation, normal sensation in both lower extremities, grade 5 muscle strength, normal muscle tone, and normal reflexes in both knee and Achilles tendons., Conclusions: Intravertebral mobile nerve sheath tumors are rare, and the marked distortion and elongation of the carrier nerve seen on MRI are important imaging features of this disease. The possible causes of tumor movement include tumor texture, location, positional changes, and altered cerebrospinal fluid dynamics. Acute changes in intraabdominal pressure caused by forceful defecation may be a high-risk factor for tumor migration. Multiple preoperative MRIs to localize the tumor are particularly important., (Copyright © 2020 Elsevier Inc. All rights reserved.)

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.

Background: No available meta-analysis was printed to systematically introduce the MPNST clinic outcome and risk factors based on largely pooled data. This systematic review and meta-analysis aimed to investigate 5-year OS rate, 5-year EFS rate, and LR rate for MPNST, and to assess potential risk factors for prognosis., Methods: Electronic articles published between January 1, 1966 and February 29, 2020 were searched and critically evaluated. The authors independently reviewed the abstracts and extracted data for 5-year OS rate, 5-year EFS rate, LR rate, and potential risk factors for prognosis., Results: Twenty-eight literatures were finally included for meta-analysis. The pooled 5-year OS rate, 5-year EFS rate, and LR rate were 49%, 37%, and 38%, respectively. The significant prognostic factors for survival were NF1 status, tumor size, depth, location, malignant grade, margin status, chemotherapy, and radiotherapy. Age and sex were not associated with survival., Conclusion: Survival and local recurrence of MPNST are poor. Worse prognosis is mainly associated with NF 1, large size, deep to fascia, high grade, metastases, and location (trunk and head and neck). Complete resection with adequate surgical margins is the mainstay protective factor of MPNST patients, following necessary adjuvant therapies.

Malignant peripheral nerve sheath tumors (MPNST) are a rare and aggressive group of tumors that are challenging to treat. Neurofibromatosis type 1 (NF-1)-associated MPNSTs have been associated with poorer clinical outcomes. The treatment options for NF-1-associated MPNSTs broadly include surgery (SG), chemotherapy (CT), and adjuvant radiotherapy (RT). Overall, the role and efficacy of CT and RT are unclear. Examination of existing literature for studies reporting on NF-1-associated MPNSTs and respective treatment-related outcomes was conducted. We conducted a systematic review according to PRISMA guidelines in PubMed/Medline and Cochrane databases of studies which reported treatment-specific outcomes in NF-1-associated MPNSTs. The literature search found 444 records after removal of duplicates. The present study included 50 patients across 12 observational studies. All of the included studies reported data on overall survival (OS 52%, n = 26/50) but mean follow-up in months among the studies and among patients varied widely, between 10.85 (SD, ± 10.38) and 192 (SD, ± 98.22). From the included studies, patients underwent either SG alone (n = 21), SG + CT (n = 10), SG + RT (n = 7), or SG + CT + RT (n = 12). The quality of evidence in the literature regarding optimal treatment options for NF-1-associated MPNSTs remains tenuous. Future retrospective and prospective comparative trials should consider adherence to a set of reporting guidelines to improve the quality of evidence in the literature with respect to individual treatment-related outcomes. The need for prospective multi-institutional efforts cannot be overstated.

Malignant peripheral nerve sheath tumours of thyroid are rare entities that can present a diagnostic dilemma. We present the case of a patient who presented with neck mass with a history of multiple neck surgeries and airway compression. The patient's previous histopathology was mistaken for Riedel's thyroiditis in an outside hospital, which delayed appropriate treatment leading to suffering on part of the patient and frustration on part of the physician. We emphasise that rare malignancies should be considered in rapidly growing neck masses that are causing airway compression, and histopathology of such tumours should be reported by expert pathologists., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Despite curative intents of treatment in localized malignant peripheral nerve sheath tumours (MPNSTs), prognosis remains poor. This study investigated survival and prognostic factors for overall survival in non-retroperitoneal and retroperitoneal MPNSTs in the Netherlands., Methods: Data were obtained from the Netherlands Cancer Registry and the Dutch Pathology Database. All primary MPNSTs were collected. Paediatric cases (age ≤18 years) and synchronous metastases were excluded from analyses. Separate Cox proportional hazard models were made for retroperitoneal and non-retroperitoneal MPNSTs., Results: A total of 629 localized adult MPNSTs (35 retroperitoneal cases, 5.5%) were included for analysis. In surgically resected patients (88.1%), radiotherapy and chemotherapy were administered in 44.2% and 6.7%, respectively. In retroperitoneal cases, significantly less radiotherapy and more chemotherapy were applied. In non-retroperitoneal MPNSTs, older age (60+), presence of NF1, size >5 cm, and deep-seated tumours were independently associated with worse survival. In retroperitoneal MPNSTs, male sex and age of 60+ years were independently associated with worse survival. Survival of R1 and that of R0 resections were similar for any location, whereas R2 resections were associated with worse outcomes. Radiotherapy and chemotherapy administrations were not associated with survival., Conclusion: In localized MPNSTs, risk stratification for survival can be done using several patient- and tumour-specific characteristics. Resectability is the most important predictor for survival in MPNSTs. No difference is present between R1 and R0 resections in both retroperitoneal and non-retroperitoneal MPNSTs. The added value of radiotherapy and chemotherapy is unclear., (Copyright © 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Malignant peripheral nerve sheath tumors (MPNSTs) are soft tissue sarcomas that arise from peripheral nerve fibers and primarily occur in the setting of neurofibromatosis (NF1). MPNST arising from the penis is very rare and may require mutilating surgery to achieve surgical cure. We previously reported a case of MPNST involving the penis in a 14-month-old boy treated with neoadjuvant chemotherapy, total penectomy, and adjuvant radiation. Here we report intermediate follow-up of the same patient, describe his subsequent genitourinary reconstruction, and discuss management dilemmas that arise following treatment of penile MPNST., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Management of intraneural perineuriomas remains controversial, largely due to the lack of knowledge regarding the natural history of these lesions., Objective: To describe the typical radiological growth pattern of intraneural perineuriomas and to determine how the pattern of growth relates to clinical progression., Methods: We performed a retrospective review of the magnetic resonance imaging (MRI) studies and serial clinical examinations of a cohort of patients with biopsy-proven intraneural perineuriomas who had 2 MRI studies at least 2 yr apart. The outcome of interest was radiological growth in length or width of the intraneural perineurioma. Radiological growth was tested for association with clinical progression., Results: Twenty patients were included in the study. By width, the lesions were on average larger on repeat imaging (P = .009). By absolute length, the lesions were on average longer on repeat imaging (P = .02). By lesion:landmark ratio, there was no difference in length of the lesions between sequential images (P = .09), with 10 (50%) lesions being shorter and 7 (35%) showing no change. No lesions grew to involve a new nerve or division of a nerve on sequential imaging. None of the variables tested were associated with clinical progression., Conclusion: We found that intraneural perineuriomas only rarely grow in length, do not grow to involve new nerves or nerve divisions, and growth does not correlate with clinical progression. These findings have significant ramifications for management of these tumors., (Copyright © 2018 by the Congress of Neurological Surgeons.)

Objectives: Malignant peripheral nerve sheath tumor (MPNST) is a rare type of soft tissue sarcoma (STS) that carries significant mortality. Given the rarity of MPNST, current knowledge on the disease is limited. We aim to characterize patient, tumor, and treatment factors, and determine variables associated with 5-year overall survival (OS) in individuals with MPNST., Materials and Methods: We utilized the National Cancer Database (NCDB) to identify adult patients diagnosed with MPNST from 2004 to 2015, and analyze patient, tumor, treatment, and survival data. American Joint Committee on Cancer (AJCC 8) staging criteria for STS was utilized., Results: In our cohort of 2,858 patients with MPNST, median age at diagnosis was 47. The 5-year OS rate was 52%. Age, race, tumor size, and treatment regimen significantly predicted 5-year OS on univariate analysis. AJCC 8 stage appeared to predict 5-year OS in head and neck tumors (though not significantly), but not trunk and extremity tumors., Conclusion: While our cohort of patients with MPNST are typically relatively young and healthy, 5-year OS is only 52%. Notably, age extremes, large tumor size, and certain treatment regimens are associated with worse outcomes. While AJCC 8 staging guidelines may have some value in predicting OS in head and neck tumors, they do not reliably risk stratify patients with trunk and extremity MPNST. Ultimately, MPNST is associated with high mortality with few modifiable risk factors, and survival may not be adequately predicted by current staging systems., (Published by Elsevier Ltd.)

A 41-year-old woman presented with a 16-year history of lumbar pain and right leg paresthesia. Twenty-four years previously, she had been diagnosed with neurofibromatosis type 1 syndrome. Magnetic resonance imaging showed a heterogeneous mass extending through widened lumbar neural foramina to the psoas muscles bilaterally, with a dumbbell-like appearance. Biopsy led to the diagnosis of a malignant peripheral nerve sheath tumor, an uncommon soft tissue sarcoma of neural origin that may occur in the context of neurofibromatosis type 1 syndrome. Given the aggressive behavior of these tumors, prompt and accurate diagnosis is critical to improve patient outcomes., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Malignant peripheral nerve sheath tumor (MPNST) is a rare invasive soft tissue sarcoma that originates from peripheral nerve branches and peripheral nerve sheaths. Early radical surgery is an effective treatment for MPNST. Since it is insensitive to radiotherapy and chemotherapy, the disease manifests a rapid progression, poor prognosis and high mortality. In recent years, the translational researches on the driving factors and therapeutic targets of MPNST have been rapidly developed, including the pathways of NF1-Ras, Raf-MEK-ERK, PI3K-AKT-mTOR, Wnt signaling, and abnormal expressions of apoptotic proteins, the general loss of polycomb repressive complex 2 (PRC2), upregulation of the HDAC family, abnormal expressions of receptor tyrosine kinases, expressions of programmed cell death ligand (PD-L1), aurora kinase and various microRNAs.This review summarizes the current translational researches on potential therapeutic targets of MPNST, and the clinical trials which provide helpful information for MPNST targeted therapy.

Malignant triton tumor (MTT) is an extraordinarily uncommon and aggressive tumor which have poor prognosis. Malignant peripheral nerve sheath tumors with additional rhabdomyoblasts are found in MTT histologically. The prognosis of patients is poor. The goal of our study is to describe the largest number of cases characteristic and outcome, to our knowledge, such a presentation was not described in the English-language literature until now.From 1999 to 2014, 10 patients (5 women and 5 men) with a malignant triton tumor were treated at our institution. All these cases were followed-up and patient charts were analyzed for outcome.In our study, 3 cases of the Malignant triton tumors originate in the head, 2 cases in the joints, 2 cases in the retroperitoneum, 2 cases in the soft tissues of the thoracic wall, and 1 case in the prostate. Neoplasm associated with pain was the main manifestation. Patients have a poor prognosis. Completely surgical excision of the tumor is the only treatment. Additional radiation or chemotherapy show little effect.Malignant triton tumor is a rare sarcoma. The high probability of developing local recurrence and distant metastases could account for its poor prognosis.

Background: Malignant peripheral nerve sheath tumors (MPNST) may be sporadic or associated with neurofibromatosis or prior radiation. MPNST may behave aggressively with a high rate of local recurrence and distant metastasis., Methods: In an IRB approved protocol, we reviewed the clinical characteristics, treatment, and outcomes of 280 patients treated for MPNST at Massachusetts General Hospital (MGH) between 1960 and 2016., Results: There were 138 men and 142 women with a median age of 41 (range: 3-95) years. Tumors were classified as neurofibromatosis-associated (nfMPNST, n = 77), radiation-induced (rMPNST, n = 21), or sporadic (sMPNST, n = 182) MPNST. The median time to development of rMPNST from prior radiation was 15 years. With a median follow-up of 43.1 months, the median overall survival (OS) was 65.3 months. Older age, nfMPNST, rMPNST, increased tumor size, lymph node involvement, metastatic disease, intermediate to high grade, radiotherapy alone, and R2 resection were related to worse OS, whereas surgery with radiotherapy was associated with improved OS. Among the 251 patients without metastasis, nfMPNST, rMPNST, and increased tumor size were correlated with worse metastasis-free survival; nfMPNST, radiotherapy alone, and R1/R2 resection were associated with local recurrence, whereas surgery with adjuvant radiotherapy was related to improved local control in patients with R1/R2 resection., Conclusions: Both radiation-induced and neurofibromatosis-associated MPNSTs have poorer prognosis than sporadic MPNSTs. Complete resection of the tumor is a significant prognostic factor for MPNST. The addition of radiotherapy after surgery should be considered especially when the surgical margins are positive., (Copyright © 2019. Published by Elsevier B.V.)

Background: Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive soft tissue sarcomas. Once metastasized, prognosis is poor despite regular treatment with conventional cytotoxic drugs. This study reviews the preclinical and clinical results of non-cytotoxic systemic therapy in MPNST., Methods: A systematic search was performed in PubMed and Embase databases according to the PRISMA guidelines. Search terms related to 'MPNST', 'targeted therapy', 'immunotherapy', and 'viral therapy' were used. Only in vivo studies and clinical trials were included. Clinicaltrials.gov was also searched for any ongoing trials including MPNST patients. Qualitative synthesis was performed on all studies stratifying per target: membrane, cytoplasmic, nuclear, immunotherapy and oncolytic viruses, and other. In vivo studies were assessed for treatment effect on tumor growth (low/intermediate/high), survival, and metastases. Clinical trials were assessed on response rate, progression-free survival, and overall survival., Results: After full-text screening, 60 in vivo studies and 19 clinical trials were included. A total of 13 trials are ongoing and unpublished. The included trials displayed relatively poor response rates thus far, with patients achieving stable disease at best. Inhibiting cytoplasmic targets most commonly yielded high treatment effect, predominantly after mTOR inhibition. Oncolytic viruses and angiogenesis inhibition also demonstrate intermediate to high effect. Therapies including a combination of drugs were most effective in controlling tumor growth. Several ongoing trials investigate potentially promising pathways, while others have yet to be established., Conclusion: Targeting the PI3K/Akt/mTOR pathway seems most promising in the treatment of MPNSTs. Oncolytic viruses and angiogenesis inhibition represent emerging therapies that require further study. Combinations of targeted therapies are most likely key to maximize treatment effect., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Malignant granular cell tumors are an extremely rare, high-grade sarcoma with a schwannian phenotype and are composed of malignant granular cells with cytoplasmic lysosomal inclusion. To date, 157 cases of malignant granular cell tumors have been reported. We report the first case of a malignant granular cell tumor arising from the digital nerve to the median nerve in the palm, and we review the 157 previously reported cases and summarize the clinical profile, treatment, and outcome of this tumor. The median age, tumor size, and follow-up periods were 51 years, 6 cm, and 24 months respectively. With respect to the oncological result, 53 patients (33.8%) had no evidence for disease, 31 (19.7%) were alive with the disease, and 51 (32.5%) died because of the disease. Our case report indicates that rare malignant tumors can arise from the digital nerve to the median nerve in the palm, an anatomical site that is usually affected by benign lesions. Exhaustive discussions between surgeons and pathologists are necessary for the treatment of this rare malignant tumor.

Malignant peripheral nerve sheath tumors (MPNSTs) are soft tissue sarcomas that develop from peripheral nerve sheath cells (T. Hirose, B.W. Scheithauer). These tumors are characterized by aggressive growth with an unfavorable outcome and may develop de novo or through malignant transformation of schwannomas, neurofibromas, or ganglioneuromas. MPNSTs are characterized by a rapid course and a poor prognosis. In this article, we reported cases of patients with malignant peripheral nerve tumors of the brachial plexus trunks and spinal localization.

Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive soft-tissue sarcomas resistant to most cancer treatments. Surgical resection remains the primary treatment, but this is often incomplete, ultimately resulting in high mortality and morbidity rates. There has been a resurgence of interest in oncolytic virotherapy because of encouraging preclinical and clinical trial results. Oncolytic herpes simplex virus (oHSV) selectively replicates in cancer cells, lysing the cell and inducing antitumor immunity. We previously showed that basal interferon (IFN) signaling increases interferon-stimulated gene (ISG) expression, restricting viral replication in almost 50% of MPNSTs. The FDA-approved drug ruxolitinib (RUX) temporarily resets this constitutively active STAT signaling and renders the tumor cells susceptible to oHSV infection in cell culture. In the studies described here, we translated our in vitro results into a syngeneic MPNST tumor model. Consistent with our previous results, murine MPNSTs exhibit a similar IFN- and ISG-mediated oHSV-resistance mechanism, and virotherapy alone provides no antitumor benefit in vivo However, pretreatment of mice with ruxolitinib reduced ISG expression, making the tumors susceptible to oHSV infection. Ruxolitinib pretreatment improved viral replication and altered the oHSV-induced immune-mediated response. Our results showed that this combination therapy increased CD8 + T-cell activation in the tumor microenvironment and that this population was indispensable for the antitumor benefit that follows from the combination of RUX and oHSV. These data suggest that JAK inhibition prior to oncolytic virus treatment augments both oHSV replication and the immunotherapeutic efficacy of oncolytic herpes virotherapy., (©2018 American Association for Cancer Research.)

The purpose of this retrospective, multicentre case series was to describe the outcome following surgery and/or radiation of spinal meningiomas and nerve sheath tumours (NSTs) based upon treatment modality, with a specific aim to evaluate the survival times and time to recurrence following treatment for each histopathological diagnosis. Our hypothesis was that the addition of radiation therapy modalities to treatment will yield longer time to recurrence of clinical signs and survival time. Thirty-four dogs met the inclusion criteria of histopathologically diagnosed extramedullary spinal meningioma or NST. Sixteen extramedullary spinal meningiomas and 18 NSTs were diagnosed. A diagnosis of meningioma was associated with a significantly longer survival time compared with NSTs, with median survival times (MST) of 508 days (95% confidence interval [CI]: 66-881) vs 187 days (95% CI: 76-433; P = .02). Dogs (seven) treated with stereotactic radiation therapy (SRT) for recurrence after surgery alone or SRT alone as their initial treatment gained an additional 125 to 346 days survival time., (© 2018 John Wiley & Sons Ltd.)

Rationale: Prostate sarcoma has been reported to represent 0.7% of primary prostate malignancies. Leiomyosarcoma and rhabdomyosarcoma are the most common sarcomas of the prostate. Malignant peripheral nerve sheath tumor (MPNST) of the prostate is very rare., Patient Concerns: A 22-year-old man presented with gross hematuria and voiding difficulty for 2 weeks. Magnetic resonance imaging showed a 6-cm mass in the left lobe of the prostate., Diagnoses: Core needle biopsy results revealed high-grade sarcoma, suggestive of poorly differentiated synovial sarcoma. The final diagnosis of laparoscopic prostatectomy was MPNST, because it did not show the presence of SYT-SSX fusion transcripts on reverse transcription polymerase chain reaction analysis., Interventions: Adjuvant radiotherapy was planned because preoperative positron emission tomography-computed tomography (CT) did not show any metastatic lesion and the resection margin was microscopically involved. However, chest CT showed multiple lung metastases a month after prostatectomy. A chemotherapeutic regimen of doxorubicin and ifosfamide was administered., Outcomes: The best response to chemotherapy was partial response. After several courses of chemotherapy, he died 9 months after the surgery., Lessons: Primary prostate sarcoma and even MPNST are extremely rare. MPNST of the prostate has seldom been reported. This report may help diagnose and manage the disease.

Intraneural perineurioma is a benign neoplasm of peripheral nerve sheath with perineurial cell origin that typically affects teenagers and young adults and tends to result in a motor-predominant neuropathy. The aim of our study is to present the epidemiology, clinical presentation, way of diagnosis and management plan in a consecutive patient series. Ninteen patients diagnosed as having intraneural perineurioma were retrospectively chart reviewed. Diagnosis was done by MRI and/or biopsy with morphological, immunohistochemical staining study confirmation. Patients assessments included gender, age, symptoms, tumor localization, radiological aspect, management and pathological confirmation.Sex ratio was 10 males to 9 females with mean age of 31.2 (15-64). All the patients presented with motor deficit, ten with sensory deficit. Upper limb was involved in 11 cases (among them 4 lesions of brachial plexus), the lower limb in 8 cases. On magnetic resonance imaging, 16 patients showed a nerve enlargement whereas 5 presented with atypical fusiform tumor. Eighteen patients were operated for excision biopsy and/or palliative treatment for their motor deficit. Anatomopathological analysis confirmed the diagnosis in seventeen cases with a morphological pseudo-onion bulb shape and/or specific immunohistochemical assay. One patient had only palliative treatment without excision biopsy. Our data confirmed the equal penetration of intraneural perineurioma to both sex and affected limb. Because of the benignity of the tumor, the surgical treatment focused on optimizing the functional outcome. A prospective study with long term follow-up is required for this under-diagnosed tumor.

Background: The aim of this study was to determine the frequency of alterations in BRAF and other RAS/RAF genes, as well as other targetable pathways in malignant peripheral nerve sheath tumors (MPNSTs). Patients and Methods: Pathology specimens were available for 2 cohorts: (1) patients with MPNST at Swedish Cancer Institute (n=17) from 2004 through 2016, and (2) patients with MPNST evaluated for >300 genomic alterations at Foundation Medicine from 2014 through 2016 (n=186; including 2 Swedish patients with BRAF -mutated MPNST). Results: Of 201 MPNSTs, 13 (6.5%) demonstrated BRAF alterations. In the Foundation Medicine cohort, 10 of 84 tumors (11.9%) with no NF1 alterations had BRAF mutations (5 were V600E, 5 other), as did 3 of 102 (2.9%) tumors with NF1 alterations (1 V600E, 2 other). In the Foundation Medicine cohort, 47% of patients had an alteration in at least one other gene in the RAS/RAF pathway (not including NF1 or BRAF ); 46% had alterations in the PI3 pathway, with 70% having alterations in at least 1 of the 2 pathways; 57% had a CDKN2A alteration (80% in BRAF -mutated and 71% in NF1 -altered patients); and 70% had an alteration in DNA repair genes. MPNST, both NF1 wild-type and NF1 -mutated, often harbor alterations in the RAS/RAF pathway as well as changes related to DNA repair and CDKN2A/B V600E and other mutations occur in BRAF , suggesting the need for second-generation activating BRAF inhibitors. The concurrence of BRAF and/or NF1 alterations with CDKN2A/B mutations, in particular, may be significant in the transformation of neurologic tumors from benign to malignant. Conclusions: All MPNSTs would benefit from a comprehensive genomic analysis. Treatments targeted to RAS/RAF , DNA repair, and CDKN2A/B pathways should be used and/or developed to treat this uncommon tumor., (Copyright © 2018 by the National Comprehensive Cancer Network.)

The future of precision medicine is heavily reliant on the use of human tissues to identify the key determinants that account for differences between individuals with the same disorder. This need is exemplified by the neurofibromatosis type 1 (NF1) neurogenetic condition. As such, individuals with NF1 are born with a germline mutation in the NF1 gene, but may develop numerous distinct neurological problems, ranging from autism and attention deficit to brain and peripheral nerve sheath tumors. Coupled with accurate preclinical mouse models, the availability of NF1 patient-derived induced pluripotent stem cells (iPSCs) provides new opportunities to define the critical factors that underlie NF1-associated nervous system disease pathogenesis and progression. In this review, we discuss the generation and potential applications of iPSC technology to the study of NF1., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The histological diagnosis of malignant peripheral nerve sheath tumor (MPNST) is challenging because of the wide morphological spectrum and suboptimal performance of conventional immunohistochemical markers. MPNST arising primarily in the bone is exceptional, and its definitive diagnosis, particularly out of the neurofibromatosis type 1 (NF1) context, is even more problematic. Recurrent inactivation of EED or SUZ12 in a majority of MPNSTs results in a complete loss of trimethylated histone H3 at lysine 27 (H3K27me3) immunoreactivity, making it a highly specific biomarker of MPNSTs. In this article, we report a case of sporadic MPNST of the proximal femur that showed complete loss of H3K27me3. The patient was treated with limb-sparing surgery and postoperative radiotherapy. He developed multiple lung and bone metastases 4 months after surgery. Our case confirms the utility of H3K27me3 immunohistochemistry to yield a definitive diagnosis of sporadic MPNST in a rare primary site.

Malignant peripheral nerve sheath tumor (MPNST) is an aggressive soft tissue sarcoma for which the only effective therapy is surgery. In 2016, an international meeting entitled "MPNST State of the Science: Outlining a Research Agenda for the Future" was convened to establish short- and long-term research priorities. Key recommendations included the: 1) development of standardized, cost-efficient fluorodeoxyglucose positron emission tomography and whole-body magnetic resonance imaging guidelines to evaluate masses concerning for MPNST; 2) development of better understanding and histologic criteria for the transformation of a plexiform neurofibroma to MPNST; 3) establishment of a centralized database to collect genetic, genomic, histologic, immunohistochemical, molecular, radiographic, treatment, and related clinical data from MPNST subspecialty centers in a standardized manner; 4) creation of accurate mouse models to study the plexiform neurofibroma-to-MPNST transition, MPNST metastasis, and drug resistance; 5) use of trial designs that minimize regulatory requirements, maximize availability to patients, consider novel secondary end points, and study patients with newly diagnosed disease. Lastly, in order to minimize delays in developing novel therapies and promote the most efficient use of research resources and patient samples, data sharing should be incentivized., (© The Author 2017. Published by Oxford University Press.)

Background: Sarcomas are a rare type of breast malignancies and malignant peripheral nerve sheath tumors of the breast are even rarer. There are no specific clinical and radiological features for the diagnosis of this tumor and histological features are also reported to be nonspecific. Therefore, immunohistochemistry is required for its diagnosis. A definitive treatment protocol is unavailable because of its rarity., Case Presentation: We report a case of a sporadic form of breast malignant peripheral nerve sheath tumor found in a 16-year-old Asian Bangladeshi girl. She experienced local recurrence and she had multiple left breast lumps four times in a very short period after repeated surgeries. However, she was later managed successfully with chemotherapy and locoregional radiotherapy. A chemotherapy protocol with ifosfamide, vincristine, and actinomycin was used and radiotherapy was given with a total dose of 50 Gy given in 25 fractions of 2 Gy by a 6 MV photon linear accelerator followed by 10 Gy boost given in 5 fractions of 2 Gy by 9 MeV electron energy. With more than 3 years of periodic follow-up, she is still well without any locoregional and metastatic recurrence., Conclusions: This report suggests proper immunohistochemical analysis whenever a breast sarcoma is found in order to find a rare histological variety. We believe that malignant peripheral nerve sheath tumor of the breast can be managed by total mastectomy followed by adjuvant chemotherapy and radiotherapy. Long-term meticulous follow-up is required to develop an optimum therapeutic strategy.

Objective: In this study, we review the institution's experience in treating malignant peripheral nerve sheath tumors (MPNSTs). A secondary aim was to compare outcomes between MPNSTs with and without neurofibromatosis type 1 (NF1)., Methods: Ninety-two patients with MPNSTs, over a period of 20 years, were reviewed. A retrospective chart review was performed. The median age was 43.5 years (range, 3-84 years) and 55.4% were female; 41 patients (44.6%) had NF1-associated tumors., Results: Mean tumor sizes were 15.8 ± 8.2 cm and 10.8 ± 6.3 cm for patients with and without NF1, respectively. Combined two- and five-year overall survival was 48.5% and 29%. Multivariate analysis confirmed the association of tumor size greater than 10 cm (hazard ratio (HR) 2.99; 95% confidence interval (CI) 1.14-7.85; p = 0.0258) and presence of NF1 (HR 3.41; 95%CI 1.88-6.19; p < 0.001) with a decreased overall survival., Conclusion: Tumor size and NF1 status were the most important predictors of overall survival in our population.

Primary chest wall tumors are rare and represent a challenging clinical entity. Preoperative work-up includes a thorough history, radiographic imaging, and a biopsy approach that does not make a future definitive resection more difficult. Treatment decisions are based on tumor histology, stage, local aggressiveness, and responsiveness to chemotherapy and radiation. Wide excision is the foundation of treatment of most malignant primary chest wall tumors. The role of radiation therapy in the neoadjuvant or adjuvant setting is to reduce local recurrence. The use of adjuvant chemotherapy is more controversial. For most primary chest wall malignancies, margin-negative resection remains the best chance of cure., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Primary neural tumors of the orbit account for approximately 10% of all orbital tumors. Different tumor entities include meningiomas, optic nerve gliomas, neurofibromas, schwannomas, malignant peripheral nerve sheath tumors, and granular cell tumors. This review summarizes current concepts regarding epidemiology, clinical presentation, diagnosis, pathology, immunohistochemistry, prognosis, and treatment for neural tumors of the orbit based on the available literature., (Copyright 2017 Asia-Pacific Academy of Ophthalmology.)

Background: Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive sarcomas that arise at an estimated frequency of 8% to 13% in individuals with neurofibromatosis type 1 (NF1). Compared with their sporadic counterparts, NF1-associated MPNSTs (NF1-MPNSTs) develop in young adults, frequently recur (approximately 50% of cases), and carry a dismal prognosis. As such, most individuals affected with NF1-MPNSTs die within 5 years of diagnosis, despite surgical resection combined with radiotherapy and chemotherapy., Methods: Clinical genomic profiling was performed using 1000 ng of DNA from 7 cases of NF1-MPNST, and bioinformatic analyses were conducted to identify genes with actionable mutations., Results: A total of 3 women and 4 men with NF1-MPNST were identified (median age, 38 years). Nonsynonymous mutations were discovered in 4 genes (neurofibromatosis type 1 [NF1], ROS proto-oncogene 1 [ROS1], tumor protein p53 [TP53], and tyrosine kinase 2 [TYK2]), which in addition were mutated in other MPNST cases in this sample set. Consistent with their occurrence in individuals with NF1, all tumors had at least 1 mutation in the NF1 gene. Whereas TP53 gene mutations are frequently observed in other cancers, ROS1 mutations are common in melanoma (15%-35%), another neural crest-derived malignancy. In contrast, TYK2 mutations are uncommon in other malignancies (<7%). In the current series, recurrent TYK2 mutations were identified in 2 cases of NF1-MPNST (30% of cases), whereas TYK2 protein overexpression was observed in 60% of MPNST cases using an independently generated tissue microarray, regardless of NF1 status., Conclusions: Clinical genomic analysis of the current series of NF1-MPNST cases found that TYK2 is a new gene mutated in MPNST. Future work will focus on examining the utility of TYK2 expression as a biomarker and therapeutic target for these cancers. Cancer 2017;123:1194-1201. © 2016 American Cancer Society., (© 2016 American Cancer Society.)

Reticular perineurioma is a rare and recently delineated morphologic variant of benign perineurioma of skin and soft tissues. Because of its nonspecific gross appearance, varying histologic patterns, and potential range of cellularity, perineurioma of the hand is likely to be confused with more commonly encountered tumor or tumor-like conditions such as schwannoma, neurofibroma, fibromyxoid tumors, and giant tumor of tendon sheath. We report the case of a 20-year-old woman who presented with a slowly growing mass of the hand, which was eventually identified as a reticular perineurioma., (Copyright © 2017 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)

Background: Immunotherapy targeting cancer-testis antigen NY-ESO-1 shows promise for tumors with poor response to chemoradiation. Malignant peripheral nerve sheath tumors (MPNSTs) and liposarcomas (LPS) are chemoresistant and have few effective treatment options. Materials Methods: Using a comprehensive tissue microarray (TMA) of both benign and malignant tumors in primary, recurrent, and metastatic samples, we examined NY-ESO-1 expression in peripheral nerve sheath tumor (PNST) and adipocytic tumors. The PNST TMA included 42 MPNSTs (spontaneous n = 26, NF1-associated n = 16), 35 neurofibromas (spontaneous n = 22, NF-1 associated n = 13), 11 schwannomas, and 18 normal nerves. The LPS TMA included 48 well-differentiated/dedifferentiated (WD/DD) LPS, 13 myxoid/round cell LPS, 3 pleomorphic LPS, 8 lipomas, 1 myelolipoma, and 3 normal adipocytic tissue samples. Stained in triplicate, NY-ESO-1 intensity and density were scored., Results: NY-ESO-1 expression was exclusive to malignant tumors. 100% of myxoid/round cell LPS demonstrated NY-ESO-1 expression, while only 6% of WD/DD LPS showed protein expression, one of which was WD LPS. Of MPNST, 4/26 (15%) spontaneous and 2/16 (12%) NF1-associated MPNSTs demonstrated NY-ESO-1 expression. Strong NY-ESO-1 expression was observed in myxoid/round cell and dedifferentiated LPS, and MPNST in primary, neoadjuvant, and metastatic settings., Conclusions: We found higher prevalence of NY-ESO-1 expression in MPNSTs than previously reported, highlighting a subset of MPNST patients who may benefit from immunotherapy. This study expands our understanding of NY-ESO-1 in WD/DD LPS and is the first demonstration of staining in a WD LPS and metastatic/recurrent myxoid/round cell LPS. These results suggest immunotherapy targeting NY-ESO-1 may benefit patients with aggressive tumors resistant to conventional therapy.

The clinical management of malignant peripheral nerve sheath tumors (MPNSTs) is challenging not only due to its aggressive and invasive nature, but also limited therapeutic options. Using gene expression profiling, our lab identified BMP2-SMAD1/5/8 pathway as a potential therapeutic target for treating MPNSTs. In this study, we explored the therapeutic impact of targeting BMP2-SMAD1/5/8 pathway in conjunction with RAS-MEK-ERK signaling, which is constitutively activated in MPNSTs. Our results indicated that single agent treatment with LDN-193189, a BMP2 Type I receptor inhibitor, did not affect the growth and survival of MPNST cells at biochemically relevant inhibitory concentrations. However, addition of a MEK1/2 inhibitor, selumetinib, to LDN-193189-treated cells resulted in significant inhibition of cell growth and induction of cell death. LDN-193189 at biochemically effective concentrations significantly inhibited motility and invasiveness of MPNST cells, and these effects were enhanced by the addition of selumetinib. Overall, our results advocate for a combinatorial therapeutic approach for MPNSTs that not only targets the growth and survival via inhibition of MEK1/2, but also its malignant spread by suppressing the activation of BMP2-SMAD1/5/8 pathway. Importantly, these studies were conducted in low-passage patient-derived MPNST cells, allowing for an investigation of the effects of the proposed drug treatments in a biologically-relevant context., Competing Interests: The authors do not have any potential conflicts of interest in regards to the submitted work.