• cosmesis
• function
• preservation
• recurrence
• vagal schwannoma

• Humans
• Female
• Male
• Middle Aged
• Neurilemmoma/surgery
• Neurilemmoma/pathology
• Adult
• Treatment Outcome
• Longitudinal Studies
• Magnetic Resonance Imaging
• Cranial Nerve Neoplasms/surgery
• Cranial Nerve Neoplasms/pathology
• Aged
• Vagus Nerve Diseases/surgery
• Vagus Nerve Diseases/pathology
• Follow-Up Studies

• CDKN2A
• NF1
• PRC2
• Genome instability
• Malignant peripheral nerve sheath tumors
• Neurofibromas

• Lesions
• Magnetic resonance imaging
• Multiparametric
• Neurofibromatosis type 1
• Whole-body MRI

• Humans
• Neurofibromatosis 1/diagnostic imaging
• Neurofibromatosis 1/pathology
• Whole Body Imaging/methods
• Multiparametric Magnetic Resonance Imaging/methods

• Brachial plexopathy
• Cancer
• Case report
• Radiation

• abdominal hemorrhage
• heterogeneous differentiation
• malignant peripheral nerve sheath tumors
• neurofibromatosis type i

• Humans
• Male
• Adult
• Neurofibromatosis 1/complications
• Retroperitoneal Neoplasms/surgery
• Retroperitoneal Neoplasms/complications
• Retroperitoneal Neoplasms/diagnosis
• Fatal Outcome
• Hemorrhage/etiology
• Nerve Sheath Neoplasms/surgery

• 20ZFY34001 the Fundamental Research Funds for the Central Universities

• Humans
• Male
• Clavicle/pathology
• Adolescent
• Nerve Sheath Neoplasms/pathology
• Nerve Sheath Neoplasms/radiotherapy
• Bone Neoplasms/pathology
• Bone Neoplasms/radiotherapy

• immunotherapy
• lung
• malignant peripheral nerve sheath tumor
• programmed death-ligand 1 expression
• sintilimab

• hoffman tinel sign
• neurilemmoma
• neurofibroma
• peripheral nerve sheath tumors
• schwannoma

• Malignant peripheral nerve sheath tumor
• Neurofibroma
• Perineurioma
• Schwannoma

• Humans
• Peripheral Nervous System Neoplasms/pathology
• Nerve Sheath Neoplasms/pathology
• Nerve Sheath Neoplasms/diagnosis
• Neurilemmoma/pathology
• Neurilemmoma/diagnosis
• Neurofibroma/pathology

• Craniospinal axis
• MPNST
• Malignant Triton tumor
• Malignant peripheral nerve sheath tumors
• Mesenchymal tumors

• Humans
• Male
• Female
• Adolescent
• Young Adult
• Adult
• Middle Aged
• Aged
• Neurofibrosarcoma/pathology
• Nerve Sheath Neoplasms/surgery
• Nerve Sheath Neoplasms/diagnosis
• Retrospective Studies
• Treatment Outcome
• Neurofibromatosis 1/pathology

• MPNST
• drug delivery
• intratumoral administration
• malignant peripheral nerve sheath tumor
• targeted therapy

• Humans
• Neurofibrosarcoma
• Nerve Sheath Neoplasms/drug therapy
• Nerve Sheath Neoplasms/pathology
• Drug Delivery Systems

• Humans
• Male
• Female
• Adult
• Neurofibrosarcoma/complications
• Nerve Sheath Neoplasms/surgery
• Neurofibroma
• Neurofibromatosis 1/complications
• Neurofibromatosis 1/diagnosis
• Neurofibromatosis 1/pathology
• Brachial Plexus
• Margins of Excision

• Adnexal mass
• Magnetic resonance imaging
• Malignant peripheral nerve sheath tumor
• Pathology

• MPNST
• MRI
• PET-scan
• nerve biopsy
• nerve tumor

• Antibodies, Monoclonal, Humanized
• B7-H1 Antigen/genetics
• B7-H1 Antigen/metabolism
• Benchmarking
• Humans
• Male
• Middle Aged
• Neoplasm Recurrence, Local
• Neurofibrosarcoma

• diagnosis
• magnetic resonance imaging
• neoplasm
• soft tissue mass
• ultrasonography

• National Natural Science Foundation of China

• neurofibromatosis type 1
• nf1
• neurofibroma
• plexiform neurofibroma
• malignant peripheral nerve sheath tumor
• mpnst

Malignant peripheral nerve sheath tumor (MPNST) is a rare soft tissue sarcoma mainly treated via surgical resection. Herein, we report a case of MPNST wherein a massive tumor thrombus extended to the major veins and heart.

A 39-year-old female with a history of neurofibromatosis type 1 developed MPNST from the right radial nerve. In addition to adjuvant chemotherapy, she underwent wide tumor resection and concomitant radial nerve resection, followed by postoperative radiotherapy. Histological evaluation revealed marked venous invasion. The 2-year follow-up CT revealed an asymptomatic recurrent tumor thrombus extending from the right subclavian vein to the heart. An urgent life-saving operation was performed to ligate the base of the right subclavian vein and remove the entire intravenous thrombus that extended to the right ventricle. The remaining tumor in the right subclavian vein increased in size 3 months after thrombectomy. After confirming the absence of any metastatic lesions, the patient underwent extended forequarter amputation to achieve surgical remission. One year later, a new metastasis to the right diaphragm was safely resected. The patient remains alive without any evidence of disease 2 years after the extended forequarter amputation.

In cases of a previous history of microscopic venous invasion, recurrence can occur as a massive tumor thrombus that extends to the great vessels.

The online version contains supplementary material available at 10.1186/s12957-021-02473-2.

• MPNST
• Tumor thrombus
• Venous invasion

Schwannoma is a benign, encapsulated and slowly growing tumor originating from Schwann cells and is rarely seen in the peripheral nerve system. Typical symptoms are soreness, radiating pain and sensory loss combined with a soft tissue mass.

To evaluate pre- and postoperative symptoms in patients operated for schwannomas in the extremities and investigate the rate of malignant transformation.

In this single center retrospective study design, all patients who had surgery for a benign schwannoma in the extremities from May 1997 to January 2018 were included. The location of the tumor in the extremities was divided into five groups; forearm, arm, shoulder, thigh and leg including foot. The locations of the tumor in the nerves were also categorized as either; proximal, distal, minor or major nerve. During the pre- and postoperative clinical evaluation, symptoms were classified as paresthesia, local pain, radiating pain, swelling, impairment of mobility/strength and asymptomatic tumors that were found incidentally (with magnetic resonance imaging). The patients were evaluated after surgery using the following categories: Asymptomatic or symptomatic patients (radiating and/or local pain) and those with complications. The follow up period was from the time of surgery until last examination of the particular physician. Multivariate logistic regression analysis was performed to identify independent prognostic factors for postoperative significant symptoms at follow-up.

We identified 858 cases from the institutional pathology register. We excluded cases with duplicate diagnoses (n = 407), pathology not including schwannomas (n = 157), lesions involving the torso, spine and neck (n = 150) leaving 144 patients for further analysis. In this group 99 patients underwent surgery and there were five complications recorded: 2 infections (treated with antibiotics) and 3 nerve palsies (2 involving the radial nerve and one involving the median nerve) that recovered spontaneously. At the end of follow-up, 1.4 mo (range 0.5-76) postoperatively, we recorded a post-operative decrease in clinical symptoms: Local pain 76% (6/25), radiating pain 97% (2/45), swelling 20% (8/10). Symptoms of paresthesia increased by 2.8% (37/36) and there was no change in motor weakness before and after surgery 1% (1/1). Multivariate analysis showed that tumors located within minor nerves had a significantly higher prevalence of postoperative symptoms compared with tumors in major nerves (odds ratio: 2.63; confidence intervals: 1.22-6.42, P = 0.029). One patient with schwannoma diagnosed by needle biopsy was diagnosed to have malignant transformation diagnosed in the surgically removed tumor. No local recurrences were reported.

Surgery of schwannomas can be conducted with low risk of postoperative complications, acceptable decrease in clinical symptoms and risk of malignant transformation is low.

• Schwannoma
• Extremities
• Surgery
• Removal
• Symptoms
• Outcome

• 3-dimensional
• exoscope
• illumination
• microscope
• neurosurgical technology
• operative field
• optics
• visualization

Atypical lipomatous tumor (ALT) has been defined as a well-differentiated liposarcoma exhibiting a higher frequency of a local recurrence after surgical resection. ALT is mainly classified into deep type and superficial type. Compared with deep type ALT, superficial type ALT is rarely observed. One of the most important issues is that little has been known about superficial type ALT and it is not easy to predict the presence of superficial type ALT before surgical resection. To clarify the clinical manifestations of superficial type ALT, we examined 15 cases with superficial type ALT and 118 cases with benign lipoma, and analyzed their differences in clinical characteristics and the findings of MRI test. In clinical characteristics, the tumor size of superficial type ALT was significantly greater than that of benign lipoma, and superficial type ALT showed a significantly higher frequency of the tumor size of more than 4 cm. Superficial type ALT exhibited poor tumor mobility and hardness with elastic soft. In addition, a significantly higher frequency of tumor location of superficial type ALT was observed in extremities. Among tumor sites at the trunk, buttocks, and shoulder were high frequent location in superficial type ALT. In an MRI examination, superficial type ALT exhibited a significantly higher frequency of the septal structures compared with benign lipoma. The combinations of clinical characteristics, including physical examinations, MRI, and histological examinations, are helpful for the diagnosis of superficial type ALT.

• atypical lipomatous tumor (ALT)
• clinical characteristics
• magnetic resonance imaging (MRI)
• physical examination
• tumor size

Among the diverse causes of posterior mediastinal masses, malignant peripheral nerve sheath tumors is a very rare neurogenic tumor. Imaging features tend to be variable. A 20-month-old toddler presented with a 3-month history of persistent diffuse thoracic and abdominal pain. A chest magnetic resonance imaging was taken and shown a posterior mediastinal lesion. Histopathology and immunohistochemical analysis confirmed the diagnosis of a malignant peripheral nerve sheath tumor with myxoid areas.

Malignant peripheral nerve sheath tumors are an uncommon entity in the children with a poor prognosis. Magnetic resonance imaging is the preferred technique in children to limit the use of ionizing radiation and because has a higher contrast resolution; however, all suspicious tumors should be biopsied to make an appropriate diagnosis. Treatment is radical surgery with excision of the entire mass; however, there is a high incidence of local recurrence.

• Child
• Malignant peripheral nerve sheath tumor
• Nerve sheath neoplasms
• Neurofibroma
• Peripheral nerve
• Schwannoma

•

MPNST arising from a gynaecological origin is rare.

Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive soft tissue sarcomas that can arise most frequently in patients with neurofibromatosis type 1 (NF1). Despite an increasing understanding of the molecular mechanisms that underlie these tumors, there remains limited therapeutic options for this aggressive disease. One potentially critical finding is that a significant proportion of MPNSTs exhibit recurrent mutations in the genes EED or SUZ12, which are key components of the polycomb repressive complex 2 (PRC2). Tumors harboring these genetic lesions lose the marker of transcriptional repression, trimethylation of lysine residue 27 on histone H3 (H3K27me3) and have dysregulated oncogenic signaling. Given the recurrence of PRC2 alterations, intensive research efforts are now underway with a focus on detailing the epigenetic and transcriptomic consequences of PRC2 loss as well as development of novel therapeutic strategies for targeting these lesions. In this review article, we will summarize the recent findings of PRC2 in MPNST tumorigenesis, including highlighting the functions of PRC2 in normal Schwann cell development and nerve injury repair, as well as provide commentary on the potential therapeutic vulnerabilities of a PRC2 deficient tumor cell.

• MPNST
• PRC2
• malignant peripheral nerve sheath tumor
• neurofibromatosis
• polycomb repressive complex

• Animals
• Humans
• Mutation
• Nerve Sheath Neoplasms/genetics
• Nerve Sheath Neoplasms/metabolism
• Nerve Sheath Neoplasms/pathology
• Polycomb Repressive Complex 2/genetics
• Polycomb Repressive Complex 2/metabolism
• Schwann Cells/metabolism
• Schwann Cells/pathology

Persistent signalling via the PI3K/AKT/mTOR pathway is a major driver of malignancy in NF1-associated malignant peripheral nerve sheath tumours (MPNST). Nevertheless, single targeting of this pathway is not sufficient to inhibit MPNST growth. In this report, we demonstrate that combined treatment with the allosteric pan-AKT inhibitor MK-2206 and the mTORC1/mTORC2 inhibitor AZD8055 has synergistic effects on the viability of MPNST cell lines in comparison to the treatment with each compound alone. However, when treating animals bearing experimental MPNST with the combined AKT/mTOR regime, no influence on tumour growth was observed. Further analysis of the MPNST xenograft tumours resistant to AKT/mTOR treatment revealed a reactivation of both AKT and mTOR in several tumour samples. Additional targeting of the RAS/RAF/MEK/MAPK pathway with the allosteric MEK1/2 inhibitor AZD6244 showed synergistic effects on the viability of MPNST cell lines in vitro in comparison to the dual AKT/mTOR inhibition. In summary, these data indicate that combined treatment with AKT and mTOR inhibitors is effective on MPNST cells in vitro but tumour resistance can occur rapidly in vivo by restoration of AKT/mTOR signalling. Our data further suggest that a triple treatment with inhibitors against AKT, mTORC1/2 and MEK1/2 may be a promising treatment option that should be further analysed in an experimental MPNST mouse model in vivo.

• AKT
• MPNST
• neurofibromatosis Type 1
• signaling
• targeted therapy
• xenograft model

Malignant peripheral nerve sheath tumors (MPNSTs) are a rare subtype of soft-tissue sarcoma, derived from a peripheral branch or the sheath of the sciatic nerve, brachial plexus, or sacral plexus. The clinical outcomes for MPNST patients with unresectable or metastatic tumors are dismal, and novel therapeutic strategies are required. Although patient-derived cancer cell lines are vital for basic research and preclinical studies, few MPNST cell lines are available from public cell banks. Therefore, the aim of this study was to establish cancer cell lines derived from MPNST patients.

We used tumor tissues from five patients with MPNSTs, including one derived from a rare bone tissue MPNST. The tumor tissues were obtained at the time of surgery and were immediately processed to establish cell lines. A patient-derived xenograft was also established when a sufficient amount of tumor tissue was available. The characterization of established cells was performed with respect to cell proliferation, spheroid formation, and invasion. The mutation status of actionable genes was monitored by NCC Oncopanel, by which the mutation of 114 genes was assessed by next-generation sequencing. The response to anti-cancer agents, including anti-cancer drugs approved for the treatment of other malignancies was investigated in the established cell lines.

We established five cell lines (NCC-MPNST1-C1, NCC-MPNST2-C1, NCC-MPNST3-C1, NCC-MPNST4-C1, and NCC-MPNST5-C1) from the original tumors, and also established patient-derived xenografts (PDXs) from which one cell line (NCC-MPNST3-X2-C1) was produced. The established MPNST cell lines proliferated continuously and formed spheroids while exhibiting distinct invasion abilities. The cell lines had typical mutations in the actionable genes, and the mutation profiles differed among the cell lines. The responsiveness to examined anti-cancer agents differed among cell lines; while the presence of an actionable gene mutation did not correspond with the response to the anticipated anti-cancer agents.

The established cell lines exhibit various characteristics, including proliferation and invasion potential. In addition, they had different mutation profiles and response to the anti-cancer agents. These observations suggest that the established cell lines will be useful for future research on MPNSTs.

• Drug screening
• Malignant peripheral nerve sheath tumor
• Primary culture
• Xenograft

• carbon ion radiotherapy
• cervical spine
• conventional radiotherapy
• malignant peripheral nerve sheath tumor

Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive soft tissue sarcomas. Combining Hsp90 inhibitors to enhance endoplasmic reticulum stress with mTOR inhibition results in dramatic MPNST shrinkage in a genetically engineered MPNST mouse model. Ganetespib is an injectable potent small molecule inhibitor of Hsp90. Sirolimus is an oral mTOR inhibitor. We sought to determine the safety, tolerability, and recommended dose of ganetespib and sirolimus in patients with refractory sarcomas and assess clinical benefits in patients with unresectable/refractory MPNSTs. Patients and Methods. In this multi-institutional, open-label, phase 1/2 study of ganetespib and sirolimus, patients ≥16 years with histologically confirmed refractory sarcoma (phase 1) or MPNST (phase 2) were eligible. A conventional 3 + 3 dose escalation design was used for phase 1. Pharmacokinetic and pharmacodynamic measures were evaluated. Primary objectives of phase 2 were to determine the clinical benefit rate (CBR) of this combination in MPNSTs. Patient-reported outcomes assessed pain.

Twenty patients were enrolled (10 per phase). Toxicities were manageable; most frequent non-DLTs were diarrhea, elevated liver transaminases, and fatigue. The recommended dose of ganetespib was 200 mg/m² intravenously on days 1, 8, and 15 with sirolimus 4 mg orally once daily with day 1 loading dose of 12 mg. In phase 1, one patient with leiomyosarcoma achieved a sustained partial response. In phase 2, no responses were observed. The median number of cycles treated was 2 (1–4). Patients did not meet the criteria for clinical benefit as defined per protocol. Pain ratings decreased or were stable.

Despite promising preclinical rationale and tolerability of the combination therapy, no responses were observed, and the study did not meet parameters for further evaluation in MPNSTs. This trial was registered with (NCT02008877).

• Epigenomics
• MPNST
• NF1
• genomics
• transcriptome

• Sarcoma of nasal cavity and para nasal sinus
• head and neck sarcoma
• malignant peripheral nerve sheath tumors

•

Malignant triton tumor (MTT) is extremely rare subset of malignant peripheral nerve sheath tumor (MPNST) which accounts for < 10% of all MPNST.

In 1938, the Malignant Triton Tumor (MTT) was first explained by Mason.

Case 1: A man aged 28 years presented with chest pain and difficulty in breathing since last five months, there was no history of cough fever or night sweats. Clinical examination was unremarkable. His routine hematological tests including tumor markers were within normal range, testicular ultrasound was normal. CT scan of thorax revealed a mass in the anterior mediastinum. CT guided biopsy revealed a malignant triton tumor.

Case 2: A 30 years old man, nonsmoker presented with history of chest tightness and feeling pressure while kneeling down since last 3 months, otherwise fit and healthy. His routine hematological investigations including tumor markers were within normal range. A CT scan of thorax revealed a large mass in the right posterior mediastinum. CT guided biopsy showed malignant triton tumor.

Case 3: A man aged 28 years presented with chest pain and difficulty in breathing since last five months, there was no history of cough fever or night sweats. Clinical examination was unremarkable. His routine hematological tests including tumor markers were within normal range, testicular ultrasound was normal. CT scan of thorax revealed a mass in the anterior mediastinum. CT guided biopsy revealed a malignant triton tumor.

Malignant peripheral nerve sheath tumors (MPNST) are uncommon sarcomatous tumors that are believed to be derived from Schwann cell or neighboring cells with perineurial differentiation. MTT is rarely reported in mediastinum, lung and heart (<10%) To the best of our knowledge, only few cases of MTT in the mediastinum have been reported in English literature, including, four were reported in the anterior mediastinum, three in the posterior mediastinum, one in the middle mediastinum and one between the ascending aorta and the main pulmonary artery. Most of the patients were young adults. We report three cases of rare mediastinal malignant triton tumors. They have been treated with palliative surgery/radical surgery +/− adjuvant therapy. The prognosis varied from a 3 month overall survival time to being alive at a 53 month follow-up period.

In conclusion we report three rare cases of mediastinal malignant triton tumor treated with radical surgical resection and post-operative radiotherapy, one patient developed lung metastasis, and two had late local recurrence. The malignant triton tumor is a lethal neoplasm which carries very poor prognosis particularly when they occur in the mediastinum because it’s very difficult to obtain wider tumor free margin due to the nature of location site.

• Chemotherapy
• Malignant triton tumor
• Mediastinum
• Radiotherapy
• Surgery

• continuous intraoperative nerve monitoring
• nerve sheath tumor
• neurilemmoma
• vagal schwannoma
• vagus nerve

• MLN8237
• MPNST
• alisertib
• aurora kinase
• malignant peripheral nerve sheath tumor
• neurofibromatosis
• oncology
• small-molecule inhibitor

• bone graft
• foot
• limb salvage
• malignant peripheral nerve sheath tumor

Autophagy is an evolutionarily conserved lysosomal degradation pathway that plays an essential role in enabling eukaryotic organisms to adapt to nutrient deprivation and other forms of environmental stress. In metazoan organisms, autophagy is essential for differentiation and normal development; however, whether the autophagy pathway promotes or inhibits tumorigenesis is controversial, and the possible mechanisms linking defective autophagy to cancer remain unclear. To determine if autophagy is important for tumor suppression, we inhibited autophagy in transgenic zebrafish via stable, tissue-specific expression of a dominant-negative autophagy protein Atg5^K130R. In heterozygous tp53 mutants, expression of dominant-negative atg5^K130R increased tumor incidence and decreased tumor latency compared to non-transgenic heterozygous tp53 mutant controls. In a tp53-deficient background, Tg(mitfa:atg5^K130R) mutantsdeveloped malignant peripheral nerve sheath tumors (MPNSTs), neuroendocrine tumors and small-cell tumors. Expression of a Sox10-dependent GFP transgene in the tumors demonstrated their origin from neural crest cells, lending support to a model in which mitfa-expressing cells can arise from sox10+ Schwann cell precursors. Tumors from the transgenic animals exhibited increased DNA damage and loss-of-heterozygosity of tp53. Taken together, our data indicate that genetic inhibition of autophagy promotes tumorigenesis in tp53 mutant zebrafish, and suggest a possible role for autophagy in the regulation of genome stability during oncogenesis.

• MPNST
• loss-of-heterozygosity
• p53
• zebrafish
• Autophagy

• Magnetic resonance imaging compatible
• malignant peripheral nerve sheath tumor
• pacemaker

Malignant peripheral nerve sheath tumors (MPNST) are rare, highly malignant, and poorly understood sarcomas. The often poor outcome of MPNST highlights the necessity of identifying prognostic predictors for this aggressive sarcoma. Here, we investigate the role of fibroblast growth factor receptor (FGFR) family members in human MPNSTs.

aCGH and bioinformatics analysis identified frequent amplification of the FGFR1 gene. FISH analysis revealed that 26.9% MPNST samples had amplification of FGFR1, with both focal and polysomy patterns observed. IHC identified that FGFR1 protein expression was positively correlated with FGFR1 gene amplification. High expression of FGFR1 protein was associated with better overall survival (OS) and was an independent prognostic predictor for OS of MPNST patients. Additionally, combined expression of FGFR1 and FGFR2 protein characterized a subtype of MPNST with better OS. FGFR4 protein was expressed 82.3% of MPNST samples, and was associated with poor disease-free survival.

We performed microarray-based comparative genomic hybridization (aCGH) profiling of two cohorts of primary MPNST tissue samples including 25 patients treated at The University of Texas MD Anderson Cancer Center and 26 patients from Tianjin Medical University Cancer Institute and Hospital. Fluorescence in situ hybridization (FISH) was used to validate the gene amplification detected by aCGH analysis. Another cohort of 63 formalin-fixed paraffin-embedded MPNST samples (including 52 samples for FISH assay) was obtained to explore FGFR1, 2, 3, and 4 protein expression by immunohistochemical (IHC) analysis.

Our integrated genomic and molecular studies provide evidence that FGFRs play different prognostic roles in MPNST.

• fibroblast growth factor receptor
• fluorescence in situ hybridization
• malignant peripheral nerve sheath tumor
• microarray-based comparative genomic hybridization
• prognosis

• PEComa
• malignant peripheral nerve sheath tumor
• perivascular epithelioid cell tumor
• retroperitoneal
• sarcoma
• solitary fibrous tumor
• undifferentiated pleomorphic sarcoma

• CK7 = cytokeratin 7
• TENS = transcutaneous electrical nerve stimulation
• eccrine spiradenoma
• neuroma
• neuropathic pain
• peripheral nerve