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Schwannoma and angiosarcoma are rare occurrences. Angiosarcoma’s occurrence in a preexisting schwannoma is a very rare event with only fifteen cases reported in the literature. We report the sixteenth case of angiosarcoma arising in a schwannoma, a 30-year-old male patient with a long-standing (15 years) history of right neck lump. The lump measured around 10x7 cm at the time of presentation and all cranial nerves were intact. We performed a fiberoptic laryngoscopy and a computed tomography scan of the head and neck with contrast. Our provisional diagnosis was a parapharyngeal space neoplasm, most likely a salivary gland malignancy. The tumor was excised surgically. On histopathology it contained two distinct tissue architectures representing a schwannoma and epithelioid angiosarcoma, also confirmed on immunohistochemistry. Literature review of these limited cases implicates a poor prognosis of the disease. The pathogenesis is uncertain, but the theories put forward suggest chronic vascular stasis or vascular endothelial proliferation as possible etiologies. The main takeaway of our report is to consider the potential of malignancy in long standing cases of schwannomas. Prompt surgical treatment should be offered, and the patient and their family be counselled for postoperative adjuvant treatment for better prognosis.

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. [ABSTRACT FROM AUTHOR]

Malignant Peripheral Nerve Sheath Tumors (MPNSTs) are aggressive sarcomas that can arise both sporadically and in patients with the genetic syndrome Neurofibromatosis type 1 (NF1). Prognosis is dismal, as large dimensions, risk of relapse, and anatomical localization make surgery poorly effective, and no therapy is known. Hence, the identification of MPNST molecular features that could be hit in an efficient and selective way is mandatory to envision treatment options. Here, we find that MPNSTs express high levels of the glycolytic enzyme Hexokinase 2 (HK2), which is known to shield cancer cells from noxious stimuli when it localizes at MAMs (mitochondria-associated membranes), contact sites between mitochondria and endoplasmic reticulum. A HK2-targeting peptide that dislodges HK2 from MAMs rapidly induces a massive death of MPNST cells. After identifying different matrix metalloproteases (MMPs) expressed in the MPNST microenvironment, we have designed HK2-targeting peptide variants that harbor cleavage sites for these MMPs, making such peptides activatable in the proximity of cancer cells. We find that the peptide carrying the MMP2/9 cleavage site is the most effective, both in inhibiting the in vitro tumorigenicity of MPNST cells and in hampering their growth in mice. Our data indicate that detaching HK2 from MAMs could pave the way for a novel anti-MPNST therapeutic strategy, which could be flexibly adapted to the protease expression features of the tumor microenvironment. [ABSTRACT FROM AUTHOR]

Schwannoma and angiosarcoma are rare occurrences. Angiosarcoma's occurrence in a preexisting schwannoma is a very rare event with only fifteen cases reported in the literature. We report the sixteenth case of angiosarcoma arising in a schwannoma, a 30-year-old male patient with a long-standing (15 years) history of right neck lump. The lump measured around 10x7 cm at the time of presentation and all cranial nerves were intact. We performed a fiberoptic laryngoscopy and a computed tomography scan of the head and neck with contrast. Our provisional diagnosis was a parapharyngeal space neoplasm, most likely a salivary gland malignancy. The tumor was excised surgically. On histopathology it contained two distinct tissue architectures representing a schwannoma and epithelioid angiosarcoma, also confirmed on immunohistochemistry. Literature review of these limited cases implicates a poor prognosis of the disease. The pathogenesis is uncertain, but the theories put forward suggest chronic vascular stasis or vascular endothelial proliferation as possible etiologies. The main takeaway of our report is to consider the potential of malignancy in long standing cases of schwannomas. Prompt surgical treatment should be offered, and the patient and their family be counselled for postoperative adjuvant treatment for better prognosis. [ABSTRACT FROM AUTHOR]

Neurofibromatosis type 1 (NF1) is a neurocutaneous disorder. Plexiform neurofibromas (PNFs) are benign tumors commonly formed in patients with NF1. PNFs have a high incidence of developing into malignant peripheral nerve sheath tumors (MPNSTs) with a 5-year survival rate of only 30%. Therefore, the accurate diagnosis and differentiation of MPNSTs from benign PNFs are critical to patient management. We studied a fluorine-18 labeled tryptophan positron emission tomography (PET) radiotracer, 1-(2-[18F]fluoroethyl)-L-tryptophan (L-[18F]FETrp), to detect NF1-associated tumors in an animal model. An ex vivo biodistribution study of L-[18F]FETrp showed a similar tracer distribution and kinetics between the wild-type and triple mutant mice with the highest uptake in the pancreas. Bone uptake was stable. Brain uptake was low during the 90-min uptake period. Static PET imaging at 60 min post-injection showed L-[18F]FETrp had a comparable tumor uptake with [1⁸F]fluorodeoxyglucose (FDG). However, L-[18F]FETrp showed a significantly higher tumor-to-brain ratio than FDG (n = 4, p < 0.05). Sixty-minute-long dynamic PET scans using the two radiotracers showed similar kidney, liver, and lung kinetics. A dysregulated tryptophan metabolism in NF1 mice was further confirmed using immunohistostaining. L-[18F]FETrp is warranted to further investigate differentiating malignant NF1 tumors from benign PNFs. The study may reveal the tryptophan–kynurenine pathway as a therapeutic target for treating NF1. [ABSTRACT FROM AUTHOR]

IntroductionMalignant 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. MethodsHere 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. ResultsMyelomodulatory 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. DiscussionIn summary, our findings provide compelling evidence for the potential to leverage viroimmunotherapy with myeloid cell targeting against MPNST and warrant further investigation.

Abstract Background Malignant peripheral nerve sheath tumors (MPNSTs) account for 3–10% of pediatric sarcomas, 50% of which occur in neurofibromatosis type 1 (NF1). Sporadic MPNSTs diagnosis may be challenging due to the absence of specific markers, apart from immunohistochemical H3K27me3 loss. DNA methylation (DNAm) profiling is a useful tool for brain and mesenchymal neoplasms categorization, and MPNSTs exhibit a specific DNAm signature. An MPNST-like group has recently been recognized, including pediatric tumors with retained H3K27me3 mark and clinical/histological features not yet well explored. This study aims to characterize the DNAm profile of pediatric/juvenile MPNSTs/MPNST-like entities and its diagnostic/prognostic relevance. Results We studied 42 tumors from two groups. Group 1 included 32 tumors histologically diagnosed as atypical neurofibroma (ANF) (N = 5) or MPNST (N = 27); group 2 comprised 10 tumors classified as MPNST-like according to Heidelberg sarcoma classifier. We performed further immunohistochemical and molecular tests to reach an integrated diagnosis. In group 1, DNAm profiling was inconclusive for ANF; while, it confirmed the original diagnosis in 12/27 MPNSTs, all occurring in NF1 patients. Five/27 MPNSTs were classified as MPNST-like: Integrated diagnosis confirmed MPNST identity for 3 cases; while, the immunophenotype supported the change to high-grade undifferentiated spindle cell sarcoma in 2 samples. The remaining 10/27 MPNSTs variably classified as schwannoma, osteosarcoma, BCOR-altered sarcoma, rhabdomyosarcoma (RMS)-MYOD1 mutant, RMS-like, and embryonal RMS or did not match with any defined entity. Molecular analysis and histologic review confirmed the diagnoses of BCOR, RMS-MYOD1 mutant, DICER1-syndrome and ERMS. Group 2 samples included 5 high-grade undifferentiated sarcomas/MPNSTs and 5 low-grade mesenchymal neoplasms. Two high-grade and 4 low-grade lesions harbored tyrosine kinase (TRK) gene fusions. By HDBSCAN clustering analysis of the whole cohort we identified two clusters mainly distinguished by H3K27me3 epigenetic signature. Exploring the copy number variation, high-grade tumors showed frequent chromosomal aberrations and CDKN2A/B loss significantly impacted on survival in the MPNSTs cohort. Conclusion DNAm profiling is a useful tool in diagnostic work-up of MPNSTs. Its application in a retrospective series collected during pre-molecular era contributed to classify morphologic mimics. The methylation group MPNST-like is a ‘hybrid’ category in pediatrics including high-grade and low-grade tumors mainly characterized by TRK alterations.

Abstract Introduction Malignant peripheral nerve sheath tumors (MPNSTs) are malignancies that demonstrate nerve sheath differentiation in the peripheral nervous system. They can occur sporadically or be associated with neurofibromatosis type 1 (NF1), an autosomal dominant neurocutaneous disorder, with up to 13% of patients developing MPNSTs in their lifetimes. Previous studies have suggested conflicting findings regarding the prognosis of NF1 for patients with MPNSTs. The elucidation of NF1 as an independent prognostic factor on mortality has implications for clinical management. We aim to investigate the role of NF1 status as an independent prognostic factor of overall survival (OS) and disease-specific survival (DSS) in MPNSTs. Methods An electronic literature search of PubMed and MEDLINE was performed on studies reporting OS or DSS outcomes of MPNSTs with and without NF1. A grey literature search by reviewing bibliographies of included studies and review articles was performed to find pertinent studies. Data was extracted and assessed in accordance with the PRISMA guidelines. A meta-analysis was performed to calculate hazard ratios (HRs) using a random-effects model. The primary and secondary outcomes were all-cause and disease-specific mortality, respectively, with NF1 as an independent prognostic factor of interest. Results A total of 59 retrospective studies involving 3602 patients fulfilled the inclusion criteria for OS analysis, and 23 studies involving 704 MPNST patients were included to evaluate DSS outcomes. There was a significant increase in the hazard of all-cause mortality (HR 1.63, 95% CI 1.45 to 1.84) and disease-specific mortality (HR 1.52, 95% CI 1.24 to 1.88) among NF1 as compared to sporadic cases. Subgroup analyses and meta-regression showed that this result was consistent regardless of the quality of the study and year of publication. Conclusion NF1 is associated with a substantially higher risk of all-cause and disease-specific mortality. This finding suggests that closer surveillance is required for NF1 patients at risk of developing MPNSTs.

Malignant peripheral nerve sheath tumors (MPNSTs) are rare sarcomas associated with Schwann cells and neurofibromatosis type 1. The cutaneous subtype of MPNST is diagnosed primarily through histological findings, but immunohistochemistry is limited because of the overlap of markers with other soft tissue tumors. Treatment involves surgical excision followed by radiotherapy. Herein, we report a 37-year-old female patient who presented with a progressive, painless, cutaneous lesion in the left frontal region. Histopathological and immunohistochemical analyses revealed spindle cell neoplastic proliferation with strong S100 and SOX10 positivity, confirming the diagnosis of cutaneous malignant peripheral nerve sheath tumors (C-MPNST). The tumor was excised, and adjuvant radiotherapy at a dose of 64 Gy. Our findings provide valuable insights into the clinical and pathological characteristics, management strategies, and prognostic factors of C-MPNSTs. [ABSTRACT FROM AUTHOR]

Abstract Background Malignant peripheral nerve sheath tumor (MPNST) is an exceedingly rare and aggressive tumor, with limited literature on its management. Herein, we present our series of surgically managed craniospinal MPNSTs, analyze their outcomes, and review the literature. Methods We retrospectively reviewed surgically managed primary craniospinal MPNSTs treated at our institution between January 2005 and May 2023. Patient demographics, tumor features, and treatment outcomes were assessed. Neurological function was quantified using the Frankel grade and Karnofsky performance scores. Descriptive statistics, rank-sum tests, and Kaplan–Meier survival analyses were performed. Results Eight patients satisfied the inclusion criteria (4 male, 4 female). The median age at presentation was 38 years (range 15–67). Most tumors were localized to the spine (75%), and 3 patients had neurofibromatosis type 1. The most common presenting symptoms were paresthesia (50%) and visual changes (13%). The median tumor size was 3 cm, and most tumors were oval-shaped (50%) with well-defined borders (75%). Six tumors were high grade (75%), and gross total resection was achieved in 5 patients, with subtotal resection in the remaining 3 patients. Postoperative radiotherapy and chemotherapy were performed in 6 (75%) and 4 (50%) cases, respectively. Local recurrence occurred in 5 (63%) cases, and distant metastases occurred in 2 (25%). The median overall survival was 26.7 months. Five (63%) patients died due to recurrence. Conclusions Primary craniospinal MPNSTs are rare and have an aggressive clinical course. Early diagnosis and treatment are essential for managing these tumors. In this single-center study with a small cohort, maximal resection, low-grade pathology, young age (

Abstract Background Malignant peripheral nerve sheath tumors (MPNSTs) are malignancies that arise or differentiate from or infiltrate peripheral nerves and account for approximately 5% of soft-tissue malignancies. Approximately half of MPNSTs develop in patients with neurofibromatosis type 1 (NF1), a hereditary disease. MPNSTs occur mainly in the trunk, proximal extremities, and neck, but can on rare occasion arise in or near the gastrointestinal tract, and intestinal complications have been reported. We describe herein a case with resection of an MPNST arising in the pelvic region. Case presentation A 51-year-old woman had undergone repeated resections for systemic neurofibrosis associated with NF1. This time, a pelvic tumor was noted on follow-up positron emission tomography computed tomography (CT). She presented with slowly progressive radiating pain in the lower extremities and was referred to our hospital for tumor resection. Contrast-enhanced CT showed a 75 × 58-mm mass in the right greater sciatic foramen directly below a 24 × 28-mm mass. Open pelvic tumor resection was performed for pelvic neurofibroma. The obturator nerve was identified lateral to the main tumor and the sciatic nerve was identified dorsally, then dissection was performed. The closed nerve was spared, while the sciatic nerve was partially dissected and the two tumors were removed. Both tumors were elastic and hard. Pathologic findings were MPNST for the large specimen and neurofibroma with atypia for the small specimen. The patient developed temporary postoperative ileus, but is generally doing well and is currently free of recurrence or radiating pain. The patient is at high risk of recurrence and close monitoring should be continued. Conclusions We encountered a rare case of MPNST. Due to the high risk of recurrence, surgery with adequate margins was performed, with a requirement for appropriate follow-up.

Immune-based therapies represent a new paradigm in the treatment of multiple cancers, where they have helped achieve durable and safe clinical responses in a growing subset of patients. While a wealth of information is available concerning the use of these agents in treating the more common malignancies, little has been reported about the use of immunotherapies against malignant peripheral nerve sheath tumors (MPNSTs), a rare form of soft tissue sarcoma that arises from the myelin sheaths that protect peripheral nerves. Surgical resection has been the mainstay of therapy in MPNSTs, but the recurrence rate is as high as 65%, and chemotherapy is generally ineffective. The immune contexture of MPNSTs, replete with macrophages and a varying degree of T cell infiltration, presents multiple opportunities to design meaningful therapeutic interventions. While preliminary results with macrophage-targeting strategies and oncolytic viruses are promising, identifying the subset of patients that respond to immune-based strategies will be a milestone. As part of our effort to help advance the use of immunotherapy for MPNSTs, here we describe recent insights regarding the immune contexture of MPNSTs, discuss emerging immune-based strategies, and provide a brief overview of potential biomarkers of response.

Purpose: Neurofibromatosis type 1 (NF1) is a complex, multisystem disorder that is characterized, among other features, by a higher risk of developing benign and malignant tumors. Despite NF1 being one of the most common autosomal dominant genetic disorders, data from adult individuals in several world regions remain elusive, including Hispanics. Methods: The present is a retrospective cohort study conducted among adult patients with a confirmed diagnosis of NF1 who attended a single cancer-reference center, the Instituto Nacional de Cancerologia in Mexico City from 2001 to 2021. Data were extracted from electronic health records and collected in an anonymous database by an NF1-expert physician in order to obtain demographic characteristics and detailed information regarding the development of tumors among this patient subgroup. All patients with malignant tumors or with benign tumors, which severely affected their quality of life, were included in this study. Results: Patient records were reviewed from 2001 to 2021. A total of N = 29 patients met the criteria, with a higher proportion of female compared with male subjects [N = 22 (75.9%) vs. N = 7 (24.1%)]. Patients had a mean age at diagnosis of tumors of 32.2 years (SD = 11.2 years). In terms of malignant neoplasms, the most frequent malignant tumor presented by patients in this cohort was malignant peripheral nerve sheath tumors (N = 7, 24.1%), this was followed by breast cancer (n = 4, 13.8% among all patients, 18.2% among female patients). Other tumors also identified in this cohort included melanoma, gastrointestinal stromal tumors, and rectal cancer. Conclusion: In Mexico, patients diagnosed with NF1 develop diverse tumors as adults. As described in other studies, the most frequent malignant tumor in this patient population is the malignant peripheral nerve sheath tumor. Further studies are required to increase the scarce information available for adult Hispanics with NF1. [ABSTRACT FROM AUTHOR]

Malignant Peripheral Nerve Sheath Tumors (MPNSTs) are aggressive sarcomas that can arise both sporadically and in patients with the genetic syndrome Neurofibromatosis type 1 (NF1). Prognosis is dismal, as large dimensions, risk of relapse, and anatomical localization make surgery poorly effective, and no therapy is known. Hence, the identification of MPNST molecular features that could be hit in an efficient and selective way is mandatory to envision treatment options. Here, we find that MPNSTs express high levels of the glycolytic enzyme Hexokinase 2 (HK2), which is known to shield cancer cells from noxious stimuli when it localizes at MAMs (mitochondria-associated membranes), contact sites between mitochondria and endoplasmic reticulum. A HK2-targeting peptide that dislodges HK2 from MAMs rapidly induces a massive death of MPNST cells. After identifying different matrix metalloproteases (MMPs) expressed in the MPNST microenvironment, we have designed HK2-targeting peptide variants that harbor cleavage sites for these MMPs, making such peptides activatable in the proximity of cancer cells. We find that the peptide carrying the MMP2/9 cleavage site is the most effective, both in inhibiting the in vitro tumorigenicity of MPNST cells and in hampering their growth in mice. Our data indicate that detaching HK2 from MAMs could pave the way for a novel anti-MPNST therapeutic strategy, which could be flexibly adapted to the protease expression features of the tumor microenvironment.

Neurofibromatosis type 1 (NF1) is a neurocutaneous disorder. Plexiform neurofibromas (PNFs) are benign tumors commonly formed in patients with NF1. PNFs have a high incidence of developing into malignant peripheral nerve sheath tumors (MPNSTs) with a 5-year survival rate of only 30%. Therefore, the accurate diagnosis and differentiation of MPNSTs from benign PNFs are critical to patient management. We studied a fluorine-18 labeled tryptophan positron emission tomography (PET) radiotracer, 1-(2-[18F]fluoroethyl)-L-tryptophan (L-[18F]FETrp), to detect NF1-associated tumors in an animal model. An ex vivo biodistribution study of L-[18F]FETrp showed a similar tracer distribution and kinetics between the wild-type and triple mutant mice with the highest uptake in the pancreas. Bone uptake was stable. Brain uptake was low during the 90-min uptake period. Static PET imaging at 60 min post-injection showed L-[18F]FETrp had a comparable tumor uptake with [1⁸F]fluorodeoxyglucose (FDG). However, L-[18F]FETrp showed a significantly higher tumor-to-brain ratio than FDG (n = 4, p < 0.05). Sixty-minute-long dynamic PET scans using the two radiotracers showed similar kidney, liver, and lung kinetics. A dysregulated tryptophan metabolism in NF1 mice was further confirmed using immunohistostaining. L-[18F]FETrp is warranted to further investigate differentiating malignant NF1 tumors from benign PNFs. The study may reveal the tryptophan–kynurenine pathway as a therapeutic target for treating NF1.

PurposeNeurofibromatosis type 1 (NF1) is a complex, multisystem disorder that is characterized, among other features, by a higher risk of developing benign and malignant tumors. Despite NF1 being one of the most common autosomal dominant genetic disorders, data from adult individuals in several world regions remain elusive, including Hispanics.MethodsThe present is a retrospective cohort study conducted among adult patients with a confirmed diagnosis of NF1 who attended a single cancer-reference center, the Instituto Nacional de Cancerología in Mexico City from 2001 to 2021. Data were extracted from electronic health records and collected in an anonymous database by an NF1-expert physician in order to obtain demographic characteristics and detailed information regarding the development of tumors among this patient subgroup. All patients with malignant tumors or with benign tumors, which severely affected their quality of life, were included in this study.ResultsPatient records were reviewed from 2001 to 2021. A total of N = 29 patients met the criteria, with a higher proportion of female compared with male subjects [N = 22 (75.9%) vs. N = 7 (24.1%)]. Patients had a mean age at diagnosis of tumors of 32.2 years (SD = 11.2 years). In terms of malignant neoplasms, the most frequent malignant tumor presented by patients in this cohort was malignant peripheral nerve sheath tumors (N = 7, 24.1%), this was followed by breast cancer (n = 4, 13.8% among all patients, 18.2% among female patients). Other tumors also identified in this cohort included melanoma, gastrointestinal stromal tumors, and rectal cancer.ConclusionIn Mexico, patients diagnosed with NF1 develop diverse tumors as adults. As described in other studies, the most frequent malignant tumor in this patient population is the malignant peripheral nerve sheath tumor. Further studies are required to increase the scarce information available for adult Hispanics with NF1.

Background: Malignant peripheral nerve sheath tumor (MPNST) is an exceedingly rare and aggressive tumor, with limited literature on its management. Herein, we present our series of surgically managed craniospinal MPNSTs, analyze their outcomes, and review the literature. Methods: We retrospectively reviewed surgically managed primary craniospinal MPNSTs treated at our institution between January 2005 and May 2023. Patient demographics, tumor features, and treatment outcomes were assessed. Neurological function was quantified using the Frankel grade and Karnofsky performance scores. Descriptive statistics, rank-sum tests, and Kaplan–Meier survival analyses were performed. Results: Eight patients satisfied the inclusion criteria (4 male, 4 female). The median age at presentation was 38 years (range 15–67). Most tumors were localized to the spine (75%), and 3 patients had neurofibromatosis type 1. The most common presenting symptoms were paresthesia (50%) and visual changes (13%). The median tumor size was 3 cm, and most tumors were oval-shaped (50%) with well-defined borders (75%). Six tumors were high grade (75%), and gross total resection was achieved in 5 patients, with subtotal resection in the remaining 3 patients. Postoperative radiotherapy and chemotherapy were performed in 6 (75%) and 4 (50%) cases, respectively. Local recurrence occurred in 5 (63%) cases, and distant metastases occurred in 2 (25%). The median overall survival was 26.7 months. Five (63%) patients died due to recurrence. Conclusions: Primary craniospinal MPNSTs are rare and have an aggressive clinical course. Early diagnosis and treatment are essential for managing these tumors. In this single-center study with a small cohort, maximal resection, low-grade pathology, young age (< 30), and adjuvant radiotherapy were associated with improved survival. [ABSTRACT FROM AUTHOR]

Malignant peripheral nerve sheath tumors (MPNSTs) arising from the trigeminal nerves are extremely rare (only 45 cases, including the present case, have been published) and have been reported to develop de novo from the peripheral nerve sheath and are not transformed from a schwannoma or neurofibroma. Here, we report a case of MPNSTs of the trigeminal nerve caused by the malignant transformation of a trigeminal schwannoma, with a particular focus on genetic considerations. After undergoing a near-total resection of a histologically typical benign schwannoma, the patient presented with regrowth of the tumor 10 years after the primary excision. Histopathologic and immunochemical examinations confirmed the recurrent tumor to be an MPNST. Comprehensive genomic analyses (FoundationOne panel-based gene assay) showed that only the recurrent MPNST sample, not the initial diagnosis of schwannoma, harbored genetic mutations, including NF1-p.R2637* and TP53-p.Y234H, candidate gene mutations associated with malignant transformation. Moreover, the results of reverse transcription polymerase chain reaction showed that the fusion of SH3PXD2A and HTRA1, which has been reported as one of the responsible genetic aberrations of schwannoma, was detected in the recurrent tumor. Taken together, we could illustrate the accumulation process of gene abnormalities for developing MPNSTs from normal cells via schwannomas. [ABSTRACT FROM AUTHOR]

Background: Malignant peripheral nerve sheath tumors (MPNSTs) are malignancies that arise or differentiate from or infiltrate peripheral nerves and account for approximately 5% of soft-tissue malignancies. Approximately half of MPNSTs develop in patients with neurofibromatosis type 1 (NF1), a hereditary disease. MPNSTs occur mainly in the trunk, proximal extremities, and neck, but can on rare occasion arise in or near the gastrointestinal tract, and intestinal complications have been reported. We describe herein a case with resection of an MPNST arising in the pelvic region. Case presentation: A 51-year-old woman had undergone repeated resections for systemic neurofibrosis associated with NF1. This time, a pelvic tumor was noted on follow-up positron emission tomography computed tomography (CT). She presented with slowly progressive radiating pain in the lower extremities and was referred to our hospital for tumor resection. Contrast-enhanced CT showed a 75 × 58-mm mass in the right greater sciatic foramen directly below a 24 × 28-mm mass. Open pelvic tumor resection was performed for pelvic neurofibroma. The obturator nerve was identified lateral to the main tumor and the sciatic nerve was identified dorsally, then dissection was performed. The closed nerve was spared, while the sciatic nerve was partially dissected and the two tumors were removed. Both tumors were elastic and hard. Pathologic findings were MPNST for the large specimen and neurofibroma with atypia for the small specimen. The patient developed temporary postoperative ileus, but is generally doing well and is currently free of recurrence or radiating pain. The patient is at high risk of recurrence and close monitoring should be continued. Conclusions: We encountered a rare case of MPNST. Due to the high risk of recurrence, surgery with adequate margins was performed, with a requirement for appropriate follow-up. [ABSTRACT FROM AUTHOR]

Background. Peripheral nerve sheath malignancies (PNSM) are a rare and aggressive group of sarcomas that can occur sporadically, after radiation therapy, or related to neurofibromatosis type 1. Loss of function of NF1, TP53, and CDKN2A genes is thought to contribute to the progression of benign neurofibroma to PNSM and is a poor prognostic sign. The optimal management of patients with this disease is currently unresolved, and specific prognostic factors have not been established. Aim. To analyze the results of surgical treatment in patients with PNSM and establish prognostic factors of overall and recurrence-free survival rate. Materials and methods. The retrospective and prospective studies enrolled adult patients with histologically confirmed PNSM treated between 1998 and 2021 at the N.N. Blokhin National Medical Research Center for Oncology. Surgical intervention was performed on 61 patients, 38 (62%) females and 23 (38%) males. The most common PNSM localization was paravertebral (22 [36%] patients), followed by retroperitoneal (14 [23%] patients), and upper and lower extremities (13 [21%] and 12 [20%] patients, respectively). Results. For PNSM patients with a history of surgery, the median overall survival (OS) was 46 months (95% confidence interval 26.165.9). The 3-year and 5-year OS was 46% and 31%, respectively. The median recurrence-free survival (RFS) was 27 months (8.745.3), and 3-year and 5-year RFS was 26% and 13%, respectively. Median OS for grade 1 malignancies was not achieved, while grade 2 and grade 3 malignancy was 53 and 33 months, respectively (p=0.033). The median RFS for grade 1, 2, and 3 tumors was 119, 43, and 15 months, respectively (p=0.078). Patients who underwent radical (R0) surgery had higher RFS (p=0.006) and OS (p0.0001). After radical (R0) surgery, the median OS was not achieved; after nonradical (R1/R2) surgery, the median was 34 months. The median RFS was 124 months after R0-resection and 48 months after R1/R2. Conclusion. The most significant prognostic factors in PNSM patients are the radicality of the surgery performed and the malignancy grade. In our study, tumor size and localization did not affect the long-term treatment results.

Background Evaluation of prior phase II trials for malignant peripheral nerve sheath tumors (MPNST) may help develop more suitable trial endpoints in future studies. Methods We analyzed outcomes of patients with recurrent or unresectable/metastatic MPNST enrolled on prior Sarcoma Alliance for Research through Collaboration (SARC) phase II trials and estimated the progression-free survival (PFS). PFS from SARC006 (NCT 00304083), the phase II trial of upfront chemotherapy in chemotherapy naïve patients, was analyzed separately. Impact of baseline enrollment characteristics on PFS was evaluated. Results Sixty-four patients (29 male, 35 female, median age 39 years (range 15-81)) with MPNST were enrolled on 1 of 5 trials of single agent or combination therapy that were determined to be inactive. Patients had received a median of 1 (range 0-5) prior systemic therapy, and most had undergone prior surgery (77%) and radiation (61%). Seventy-three percent had metastatic disease at enrollment. Median PFS was 1.77 months (95% CI, 1.61-3.45), and the PFS rate at 4 months was 15%. Greater number of prior systemic therapies and worse performance status were associated with inferior PFS. There was no significant difference in PFS based on age at enrollment, treatment trial, response criteria, presence of metastatic disease, disease site at enrollment, and prior surgery or radiation. In comparison, on the SARC006 trial the PFS rate at 4 months was 94% in 40 patients. Conclusion These data provide a historical baseline PFS that may be used as a comparator in future clinical trials for patients with MPNST. [ABSTRACT FROM AUTHOR]

Peripheral nerve sheath tumors (PNST) are one of the most common neoplasms, with classical morphology and histopathological features, but they can be diagnostically challenging at times. Albeit well defined subtypes of PNST have been described in literature, but controversies regarding reporting and typing of these tumors persists. Malignant PNSTs represent a diagnostically challenging group. Although the diagnosis and classification of most PNST are relatively straightforward, borderline grey zone neoplasms continue to be a diagnostic difficulty. In our case series, we attempt in providing some useful information for the oncopathologist to help navigate these persistent and challenging problems. In the present study, we found 26 cases of PNST, out of which the most common was schwannoma (n=18), followed by neurofibroma (n=7) and one case of malignant type, that is, malignant PNST. The cases involving all age from 12 to 65 years, showing slight male preponderance.

Tumor hypoxia drives resistance to many cancer therapies, including radiotherapy and chemotherapy. Methods that increase tumor oxygen pressures, such as hyperbaric oxygen therapy and microbubble infusion, are utilized to improve the responses to current standard‐of‐care therapies. However, key obstacles remain, in particular delivery of oxygen at the appropriate dose and with optimal pharmacokinetics. Toward overcoming these hurdles, gas‐entrapping materials (GeMs) that are capable of tunable oxygen release are formulated. It is shown that injection or implantation of these materials into tumors can mitigate tumor hypoxia by delivering oxygen locally and that these GeMs enhance responsiveness to radiation and chemotherapy in multiple tumor types. This paper also demonstrates, by comparing an oxygen (O2)‐GeM to a sham GeM, that the former generates an antitumorigenic and immunogenic tumor microenvironment in malignant peripheral nerve sheath tumors. Collectively the results indicate that the use of O2‐GeMs is promising as an adjunctive strategy for the treatment of solid tumors. [ABSTRACT FROM AUTHOR]

Abstract Tumor hypoxia drives resistance to many cancer therapies, including radiotherapy and chemotherapy. Methods that increase tumor oxygen pressures, such as hyperbaric oxygen therapy and microbubble infusion, are utilized to improve the responses to current standard‐of‐care therapies. However, key obstacles remain, in particular delivery of oxygen at the appropriate dose and with optimal pharmacokinetics. Toward overcoming these hurdles, gas‐entrapping materials (GeMs) that are capable of tunable oxygen release are formulated. It is shown that injection or implantation of these materials into tumors can mitigate tumor hypoxia by delivering oxygen locally and that these GeMs enhance responsiveness to radiation and chemotherapy in multiple tumor types. This paper also demonstrates, by comparing an oxygen (O2)‐GeM to a sham GeM, that the former generates an antitumorigenic and immunogenic tumor microenvironment in malignant peripheral nerve sheath tumors. Collectively the results indicate that the use of O2‐GeMs is promising as an adjunctive strategy for the treatment of solid tumors.

Background: Currently, malignant peripheral nerve sheath tumors (MPNST) are the subject of intense research interest. However, bibliometric studies have not been conducted in this field. The purpose of the study was to identify historical trends and presents a bibliometric analysis of the MPNST literature from 2000 to 2022. Methods: For the bibliometric analysis, publications were retrieved from the Web of Science database based on the following search terms: [TI = (MPNST) OR TI= (malignant peripheral nerve sheath tumors) AND PY = (2000-2022)]. The following information was collected for each document: the publication trends and geographical distribution, important authors and collaboration, keyword distribution and evaluation, most popular journals, and most influential articles. Results: We included 1400 documents for bibliometric analysis, covering five categories: 824 articles, 17 proceedings papers, 68 letters, 402 meeting abstracts, and 89 reviews. Corrections, editorials, book chapters, data papers, publications with expressed concerns, and retractions were excluded from our research. Conclusion: Since 2000, the number of publications on MPNST has continuously increased. Among all countries that contributed to the MPNST research, the USA, Japan, and China were the three most productive countries. The journal Modern Pathology has the most publications on MPNST, while those in the Cancer Research journal were the most frequently cited. The University of Texas MD Anderson Cancer Center may be a good partner to collaborate with. Recent research trends in MPNST have focused on tumorigenesis, clinical management, and predictive biomarkers. [ABSTRACT FROM AUTHOR]

Brachial plexopathy (BP) is easily misdiagnosed due to its complexity and varying clinical presentation. Malignant peripheral nerve sheath tumors (MPNST) can accumulate in the brachial plexus and share symptoms with BP, which may hinder the differential diagnosis between BP induced by radiation or metastases, and MPNST-derived BP, in patients with a history of breast cancer and radiation exposure. A 34-year-old Chinese female presented with MPNST. The tumor involved the brachial plexus. She had a history of breast cancer and radiotherapy. The first consideration was radiation- or breast cancer metastasis-derived BP. Clinical examination was performed. Finally, a diagnosis of MPNST of the brachial plexus was made, which guided an accurate treatment plan. This report highlights the importance of correctly diagnosing BP etiology for guiding precise treatment. BP caused by MPNST needs to be considered in clinical practice, and biopsy plays a central role in the differential diagnosis. Complete local surgical resection can prolong survival of patients with MPNST and improve treatment prognosis. [ABSTRACT FROM AUTHOR]

Objectives: The objectives were to identify the key features of malignant and benign peripheral nerve sheath tumors (PNSTs) and determine a strategy for differentiating them using sonography. Methods: Forty‐six malignant peripheral nerve sheath tumors (MPNSTs) and 83 benign peripheral nerve sheath tumors (BPNSTs) confirmed by pathology from April 2010 to July 2021 were included. The general data and grayscale and color Doppler ultrasonic manifestations were compared between the two groups. We used single factor, multifactor, and area under the receiver operating characteristic (ROC) curve analyses to extract significant malignant risk factors and then established a scoring system with these factors. Results: The significant variables identified in univariate analysis (P <.05) were maximum diameter, location, shape, boundary, encapsulation, echogenicity, texture pattern, calcification, entering or exiting nerve, and vascularity. Shape, boundary and vascularity were significant risk factors, and a scoring system was established. The area under the ROC curve (0.925) confirmed the usefulness of the scoring system for differentiating MPNSTs and BPNSTs. Conclusions: Ultrasonography is an effective method for differentiating MPNSTs from BPNSTs. [ABSTRACT FROM AUTHOR]

Malignant peripheral nerve sheath tumors (MPNSTs) are rare and aggressive soft tissue sarcomas of neural origin. Approximately 50% of MPNSTs are associated with neurofibromatosis type 1 (NF1), a neurocutaneous condition characterized by skin discoloration. MPNSTs occur in approximately 4% of patients with NF1. Malignancy should be suspected when a large mass consistent with a neurofibroma is observed with heterogeneity on a radiologic examination. In our case, immunohistochemistry revealed the presence of antigens for both the tumor protein p53 and the proliferation marker Ki-67 (MKI67). In particular, MKI67 positivity helped to differentiate MPNST from neurofibroma. Complete surgical resection is the standard treatment. After surgery, radiation therapy is typically administered to the resection area to reduce the likelihood of recurrence. Following treatment, patients should undergo regular clinical follow-up using a combination of magnetic resonance imaging, computed tomography, and bone scanning for several years to monitor them for possible metastasis.

Background: Malignant peripheral nerve sheath tumors (MPNSTs) are an aggressive form of sarcomas with a poor prognosis and limited treatment options. Therefore, new therapeutic targets are urgently needed to identify novel drugs. Methods: Based on the Gene Expression Omnibus database, an integrated analysis was performed to identify differentially expressed genes (DEGs) in MPNSTs compared to neurofibromas (NFs). Then functional enrichment analyses, protein-protein interaction (PPI) network construction, and hub gene selection were conducted. We explored DEG-guided repurposable drugs to treat MPNST based on the Library of Integrated Network-Based Cellular Signatures (LINCS) database. Furthermore, the binding affinity between predicted drug candidates and the MPNST-associated hub gene was calculated using molecular docking. Results: We identified 89 DEGs in common with all three MPNSTs datasets. In the PPI networks, twist family bHLH transcription factor 1 (Twist1) with higher node degrees was further evaluated as a therapeutic target. Cytochalasin-d, cabozantinib, everolimus, refametinib, and BGT-226 were extracted from the LINCS database, which showed lower normalized connectivity scores (–1.88, –1.81, –1.78, –1.76, and –1.72, respectively) and was considered as drug candidates. In addition, the results of molecular docking between the five drugs and Twist1 showed a binding affinity of –6.61, –7.03, –7.73, –3.94, and –7.07 kcal/mol, respectively. Conclusions: Overall, our results describe the importance of Twist1 in MPNST pathogenesis. Everolimus was also found to be a potential therapeutic drug for MPNSTs.

This document is a corrigendum for an article titled "Myelomodulatory treatments augment the therapeutic benefit of oncolytic viroimmunotherapy in murine models of malignant peripheral nerve sheath tumors." The corrigendum addresses an error in the legend for Figure 1, where the tumor models were mistakenly referred to as xenografts instead of syngeneic models. The corrected legend clarifies that the study used syngeneic tumor models. The authors apologize for the error and state that it does not affect the scientific conclusions of the article. [Extracted from the article]

Peripheral nerve sheath tumors (PNST) are one of the most common neoplasms, with classical morphology and histopathological features, but they can be diagnostically challenging at times. Albeit well defined subtypes of PNST have been described in literature, but controversies regarding reporting and typing of these tumors persists. Malignant PNSTs represent a diagnostically challenging group. Although the diagnosis and classification of most PNST are relatively straightforward, borderline grey zone neoplasms continue to be a diagnostic difficulty. In our case series, we attempt in providing some useful information for the oncopathologist to help navigate these persistent and challenging problems. In the present study, we found 26 cases of PNST, out of which the most common was schwannoma (n=18), followed by neurofibroma (n=7) and one case of malignant type, that is, malignant PNST. The cases involving all age from 12 to 65 years, showing slight male preponderance. [ABSTRACT FROM AUTHOR]

Pseudoprogression, defined as the radiographic false appearance of disease progression, is not frequently observed in patients with malignant peripheral nerve sheath tumor (MPNST). We report on a case of a patient with neurofibromatosis type 1 (NF1) MPNST pseudoprogression that presented as suspected local recurrence 9.5 years after last treatment. The patient underwent surgical resection following growth of a mass on sequential MRI imaging; surgical pathology, however, showed skeletal muscle with atrophy, fibroadipose tissue, and fat necrosis, without any evidence of tumor. As MPNST survival rates increase, physicians should consider pseudoprogression as a potential presentation after prior treatment.

Background: Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive sarcomas that typically carry a dismal prognosis. Given the insensitivity of these tumors to traditional chemotherapy and the absence of effective targeted drugs, new therapeutic strategies are urgently needed. Photothermal therapy (PTT) including near-infrared laser at the third biowindow (NIR-III) has demonstrated significant potential in cancer theranostics due to its minimally invasive nature and excellent therapeutic outcomes. However, the passive utilization of photothermal agents (PTAs) with poor target specificity and biocompatibility substantially hinders the clinical translation and application of this method. Methods: We evaluated the efficiency, safety, and underlying mechanisms of NIR-III without PTAs in the treatment of MPNSTs. The photothermal performance and tissue penetration capability of the NIR-III laser were evaluated in human MPNST cell lines using CCK-8, Calcein-AM and propidium iodide (PI) staining, and Annexin V-FITC/PI assays. The tumor xenografted mice model was used for evaluating the efficacy and biosafety of NIR-III photothermal ablation. Finally, the underlying mechanisms of NIR-III treatment, explored by whole-transcriptome sequencing, are further verified by RT-qPCR. Results: We found that although the NIR-III photothermal treatment efficiency varied among individuals, which was possibly influenced by different endoplasmic reticulum stress responses, the expected antineoplastic effect was ultimately achieved after adjustment of the power density and radiation duration. Conclusions: The present study provides an intriguing noninvasive therapy for MPNSTs that accelerates the clinical translation of PTT while avoiding the biocompatibility issues arising from PTAs. Funding: This work was supported by grants from National Natural Science Foundation of China (82102344; 82172228); Shanghai Rising Star Program supported by Science and Technology Commission of Shanghai Municipality (20QA1405600); Natural Science Foundation of Shanghai (22ZR1422300); Science and Technology Commission of Shanghai Municipality (19JC1413) ; “Chenguang Program” supported by Shanghai Education Development Foundation (SHEDF) (19CG18); Shanghai Municipal Key Clinical Specialty (shslczdzk00901); Innovative research team of high-level local universities in Shanghai (SSMU-ZDCX20180700).

Neurofibromatosis type 1 (NF1) is among the most common neurogenic disorders, characterized by loss of function mutations in the neurofibromin gene (NF1). NF1 patients are extremely susceptible to developing neurofibromas, which can transform into deadly malignant peripheral nerve sheath tumors (MPNSTs). At the center of these tumors are NF1-null Schwann cells. Here, we found that nanomedicine shows promise in the treatment of NF1-associated MPNSTs. We assessed the cytotoxicity of silver nanoparticles (AgNPs) in NF1-null NF1-associated MPNSTs, NF1-wildtype sporadic MPNST, and normal Schwann cells. Our data show that AgNP are selectivity cytotoxic to NF1-associated MPNSTs relative to sporadic MPNST and Schwann cells. Furthermore, we found that sensitivity to AgNPs is correlated with the expression levels of functional neurofibromin. The restoration of functional neurofibromin in NF1-associated MPNSTs reduces AgNP sensitivity, and the knockdown of neurofibromin in Schwann cells increases AgNP sensitivity. This finding is unique to AgNPs, as NF1 restoration does not alter sensitivity to standard of care chemotherapy doxorubicin in NF1-associated MPNSTs. Using an in vitro model system, we then found that AgNP can selectively eradicate NF1-associated MPNSTs in co-culture with Schwann cells at doses tolerable to normal cells. AgNP represents a novel therapy for the treatment of NF1-associated MPNSTs and addresses significant unmet clinical need. [ABSTRACT FROM AUTHOR]

Objective: Peripheral nerve sheath tumors (PNSTs) commonly arise from peripheral nerve roots and grow locally invasive. Malignant PNSTs (mPNSTs) represent aggressive sarcomas of neural origin that can originate from PNSTs. Radiation therapy is commonly used as part of the required multimodal treatment. However, both entities tend to occur early in life and are associated with the genetic disorder neurofibromatosis type 1 (NF-1), which is known to cause increased radiosensitivity. Pencil beam scanning proton therapy (PBSPT) allows for a minimization of the dose delivered to organs at risk and the integral dose and, thus, potentially also a reduction of radiation-induced adverse events. We report the clinical outcome and toxicity rates of patients with (m)PNSTs treated with PBSPT. Methods: We retrospectively reviewed 36 patients who received PBSPT (median dose, 64 GyRBE) with curative intent for (m)PNSTs between 1999 and 2020 at our institute. Twenty-eight (78%) and 8 (22%) patients were treated at diagnosis and for tumor recurrence/progression, respectively. The median age was 32 years (range, 3–75), and 25 (69%) patients were male. mPNST and PNST were diagnosed in 31 (86%) and 5 (14%) patients, respectively. Underlying NF-1 disease was found in 8 (22%) patients. Acute and late toxicities were recorded according to Common Terminology Criteria for Adverse Events, version 4.1 (CTCAE v4.1). Overall survival (OS), local control (LC), and distant control (DC) were estimated using the Kaplan–Meier method. Results: With a median follow-up time of 31 months (range, 4–194), 13 (36%) patients died from a progressive disease, 8 (22%) experienced local failure, and 14 (39%) experienced distant failure after PBSPT. Estimated 2-year OS, LC, and DC were 75.5%, 73.5%, and 61.2%, respectively. Acute grade 3 toxicity (dermatitis, mucositis, and pain) was observed in 5 (14%) patients. Late grade 3 cataract and osteonecrosis were both observed in 1 (3%) patient at 34 and 194 months after PBSPT, respectively. There was no late grade >3 toxicity or radiation-induced secondary cancer. Conclusion: To our knowledge, this is the first study to analyze the outcome of (m)PNSTs treated with proton therapy using a PBS delivery paradigm. In our cohort, consisting mainly of patients with mPNSTs, we report reasonable oncological outcomes and low toxicity rates after PBSPT. [ABSTRACT FROM AUTHOR]

ObjectivePeripheral nerve sheath tumors (PNSTs) commonly arise from peripheral nerve roots and grow locally invasive. Malignant PNSTs (mPNSTs) represent aggressive sarcomas of neural origin that can originate from PNSTs. Radiation therapy is commonly used as part of the required multimodal treatment. However, both entities tend to occur early in life and are associated with the genetic disorder neurofibromatosis type 1 (NF-1), which is known to cause increased radiosensitivity. Pencil beam scanning proton therapy (PBSPT) allows for a minimization of the dose delivered to organs at risk and the integral dose and, thus, potentially also a reduction of radiation-induced adverse events. We report the clinical outcome and toxicity rates of patients with (m)PNSTs treated with PBSPT.MethodsWe retrospectively reviewed 36 patients who received PBSPT (median dose, 64 GyRBE) with curative intent for (m)PNSTs between 1999 and 2020 at our institute. Twenty-eight (78%) and 8 (22%) patients were treated at diagnosis and for tumor recurrence/progression, respectively. The median age was 32 years (range, 3–75), and 25 (69%) patients were male. mPNST and PNST were diagnosed in 31 (86%) and 5 (14%) patients, respectively. Underlying NF-1 disease was found in 8 (22%) patients. Acute and late toxicities were recorded according to Common Terminology Criteria for Adverse Events, version 4.1 (CTCAE v4.1). Overall survival (OS), local control (LC), and distant control (DC) were estimated using the Kaplan–Meier method.ResultsWith a median follow-up time of 31 months (range, 4–194), 13 (36%) patients died from a progressive disease, 8 (22%) experienced local failure, and 14 (39%) experienced distant failure after PBSPT. Estimated 2-year OS, LC, and DC were 75.5%, 73.5%, and 61.2%, respectively. Acute grade 3 toxicity (dermatitis, mucositis, and pain) was observed in 5 (14%) patients. Late grade 3 cataract and osteonecrosis were both observed in 1 (3%) patient at 34 and 194 months after PBSPT, respectively. There was no late grade >3 toxicity or radiation-induced secondary cancer.ConclusionTo our knowledge, this is the first study to analyze the outcome of (m)PNSTs treated with proton therapy using a PBS delivery paradigm. In our cohort, consisting mainly of patients with mPNSTs, we report reasonable oncological outcomes and low toxicity rates after PBSPT.

Malignant peripheral nerve sheath tumors (MPNSTs) are a rare subtype of mesenchymal tumors that arise from the sheath of peripheral nerves. MPNSTs exhibit strong metastatic potential, leading to poor clinical outcomes. The clinical utility of radiation therapy and chemotherapy is marginal with respect to overall survival and effective systematic therapies for MPNSTs are still needed to improve patient outcome. Although patient-derived cell lines are an essential tool for the development of novel therapies, only a limited number of cell lines have been reported and are available from cell banks. Thus, we established the novel MPNST cell line, NCC-MPNST6-C1, using surgically resected MPNST tissue. The NCC-MPNST6-C1 cells retained copy-number alterations similar to those of the original tumors and demonstrated constant proliferation, spheroid formation, and invasion capability in vitro, which reflected the malignant features of the original tumor tissue. While the NCC-MPNST6-C1 cells did not exhibit tumorigenesis in nude mice, their use in drug screening resulted in anti-cancer agents with low IC50 values. Hence, we conclude that the NCC-MPNST6-C1 cell line is a useful resource for the study of MPNSTs. [ABSTRACT FROM AUTHOR]

Background: Malignant peripheral nerve sheath tumors (MPNSTs) typically found in the trunk, limbs, head, and neck represent 3-10% of all soft-tissue sarcomas. Although they typically originating from peripheral nerve Schwann cells, 2-3% arise from the spinal nerves and may be found within the spinal canal. Here, we present a 43-year-old male with an extradural thoracic MPNST contributing to marked cord compression and a progressive paraparesis. Case Description: A 43-year-old male presented with a progressive paraparesis of 16 months' duration. The MRI showed a posterior T2-T4 extradural tumor in the thoracic spine resulting in significant cord compression. Following a T2-T4 laminectomy and gross total excision of the epidural mass, the patient regained modest neurological function. Immunohistochemistry staining supported the diagnosis of thoracic spinal MPNST. Conclusion: Rarely, spinal MPNST can be considered amongst the differential diagnoses of an extradural spinal tumor. In this case, gross total excision of a posterior T2-T4 epidural MPNST resulted in improvement in the patient's original paraparesis. Notably, immunohistochemistry staining helped confirm the diagnosis of a MPNST. [ABSTRACT FROM AUTHOR]

Neurofibromatosis 1 is a relatively rare genetic disease characterized by widespread neurofibromas originating from the peripheral nervous system. Most growths are benign, but some carry a risk of transformation to malignant peripheral nerve sheath tumors. Although these growths can be found anywhere in the body, they are rarely found in the male external genitalia. This report discusses a case of a 25-year-old male patient with neurofibromatosis 1 presenting with a scrotal mass found to have a very large para-testicular intra-scrotal malignant peripheral nerve sheath tumor that required testicle-sparing radical penectomy.

Pseudoprogression, defined as the radiographic false appearance of disease progression, is not frequently observed in patients with malignant peripheral nerve sheath tumor (MPNST). We report on a case of a patient with neurofibromatosis type 1 (NF1) MPNST pseudoprogression that presented as suspected local recurrence 9.5 years after last treatment. The patient underwent surgical resection following growth of a mass on sequential MRI imaging; surgical pathology, however, showed skeletal muscle with atrophy, fibroadipose tissue, and fat necrosis, without any evidence of tumor. As MPNST survival rates increase, physicians should consider pseudoprogression as a potential presentation after prior treatment. [ABSTRACT FROM AUTHOR]

Abstract Although extremely rare, sarcomas including malignant peripheral nerve sheath tumors should be considered in the differential diagnosis of sino‐nasal tract lesions. Long‐term cure is possible through definitive operative management followed by adjuvant therapy.