Materiały źródłowe

• #1 Diagnosis and management of malignant peripheral nerve sheath tumors: Current practice and future perspectives

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7317062/

  One of the most common malignancies affecting adults with the neurofibromatosis type 1 (NF1) cancer predisposition syndrome is the malignant peripheral nerve sheath tumor (MPNST), a highly aggressive sarcoma that typically develops from benign plexiform neurofibromas. […] This manuscript will review the current understanding of the cellular and molecular progression of MPNST, diagnostic workup of patients with these tumors, current treatment paradigms, and investigational treatment options. Additionally, we highlight novel areas of preclinical research, which may lead to future clinical trials. In summary, MPNST remains a diagnostic and therapeutic challenge, and future work is needed to develop novel and rational combinational therapy for these tumors. […] Establishing an accurate diagnosis represents a major challenge in managing patients with NF1-associated PN, AN, and MPNST.

• #1 Malignant Peripheral Nerve Sheath Tumors—A Comprehensive Review of Pathophysiology, Diagnosis, and Multidisciplinary Management

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8774267/

  MPNSTs are the former, as their presence does not specifically define the presence of Neurofibromatosis type 1 (NF1), nor are they required for its diagnosis. […] Although the most common neoplasms seen in patients with NF1 are benign neurofibromas, MPNSTs are the most common malignant neoplasm in this population, occurring in approximately 10% of patients with NF1. […] Patients with NF1 are therefore at increased risk for multiple neoplastic processes including MPNSTs. […] A particular characteristic of NF1 is the extreme heterogeneity of its clinical manifestations, which may vary wildly even among members of the same kindred. […] Patients with whole-gene deletions of NF1, subcutaneous neurofibromas, or a larger number of plexiform neurofibromas are at particular risk of developing MPNST.

• #1 Malignant Peripheral Nerve Sheath Tumour – SFA

  https://curesarcoma.org/sarcoma-subtypes/malignant-peripheral-nerve-sheath-tumour/

  Malignant peripheral nerve sheath tumor (MPNST) is a malignant spindle cell tumor often arising from a peripheral nerve, from a pre-existing benign nerve sheath tumor, or in a patient with neurofibromatosis type 1 (NF1). […] In the absence of these settings, particularly in sporadic de novo or radiotherapy-associated tumors, the diagnosis can be more challenging and is based on the histological and immunohistochemical features suggesting Schwannian differentiation. […] The presenting symptoms are an enlarging painful or painless mass that may be palpable or identified on imaging studies. […] There are no specific imaging characteristics that distinguish MPNST from other sarcomas, except possible origin from a large nerve or from neurofibromas in patients with NF1. […] The FDG PET imaging technique is sensitive but not specific in detecting MPNSTs in patients with NF1.

• #1 A Discussion of Malignant Peripheral Nerve Sheath Tumors (MPNSTs) – Neurofibromatosis Program

  https://www.uab.edu/medicine/nfprogram/blog/blog-archive/a-discussion-of-malignant-peripheral-nerve-sheath-tumors-mpnsts

  The focus of this months blog post is a discussion of malignant peripheral nerve sheath tumors (MPNSTs), which represent one of the few potentially life-threatening complications of neurofibromatosis type 1. […] Because MPNSTs are very challenging to treat, early diagnosis is critical. MPNSTs can be hard to recognize, and the diagnosis is often late because individuals are either not aware the tumors are there or do not recognize changes in neurofibromas that should be investigated. […] If a malignancy is suspected based on clinical features, an MRI is usually performed. While MRI will not diagnose a malignancy, it can indicate areas of a tumor where cells have deteriorated that are characteristic of a malignancy. […] Treatment of MPNSTs usually involves surgery to resect the tumor, if possible. […] In conclusion, because MPNSTs are difficult to treat, early detection is critically important. Individuals with NF1 should report instances of chronic pain or rapidly growing tumors.

• #1 Malignant peripheral nerve sheath tumors | UM Health-Sparrow

  https://www.uofmhealthsparrow.org/departments-conditions/conditions/malignant-peripheral-nerve-sheath-tumors

  Tests and procedures used to diagnose malignant peripheral nerve sheath tumors include: […] A detailed exam of the nervous system, known as a neurological exam, helps a health care provider gather clues for diagnosis. […] Imaging tests make pictures of the body. The pictures might help providers see the size of the cancer and whether it has spread to other parts of the body. Tests might include magnetic resonance imaging, also called MRI, or magnetic resonance neurography. Other tests might include computed tomography, also called CT scan, and positron emission tomography, also called PET scan. […] A biopsy is a procedure to remove a sample of tissue for testing in a lab. The tissue might be removed using a needle that is put through the skin and into the cancer. Sometimes surgery is needed to get the tissue sample. […] The sample is tested in a lab to see if it is cancer. Other special tests give more details about the cancer cells. The health care team uses this information to make a treatment plan.

• #1 Malignant Peripheral Nerve Sheath Tumors: Latest Concepts in Disease Pathogenesis and Clinical Management

  https://www.mdpi.com/2072-6694/15/4/1077

  Magnetic resonance imaging (MRI) is one of the most commonly utilized imaging techniques for soft tissue sarcomas. With the advancement of MRI technology, its sensitivity and specificity in tumor diagnosis are constantly improving. MRI images of MPNST revealed a low signal in T1WI and a strong signal in T2WI. Some unusual symptoms, such as invasion of fat planes, heterogeneity, ill-defined margins, and edema surrounding the lesion, have been linked to MPNST. Broski et al. found that perilesional edema, cystic degeneration or necrosis, and irregular margins can attain 100% specificity when these three signs are met simultaneously. Yun et al. devised a scoring system combining the clinical presentations and imaging characteristics to achieve 100% sensitivity and specificity in MPNST diagnosis, although further validation is still needed. A meta-analysis summarized the role of different MRI sequences in the differential diagnosis of MPNST and benign peripheral nerve sheath tumor (BPNST) and found that minimum apparent diffusion coefficient (ADCmin) alone could achieve nearly 100% sensitivity. In comparison, diffusion weighted imaging (DWI) and ADC sequences could achieve 95% specificity. The studies above have proven the efficacy of MRI in MPNST diagnosis; however, it is seldom used as a gold standard in clinical practice.

• #1 Malignant peripheral nerve sheath tumor | Radiology Reference Article | Radiopaedia.org

  https://radiopaedia.org/articles/malignant-peripheral-nerve-sheath-tumour?lang=us

  Malignant peripheral nerve sheath tumors (MPNSTs) are forms of peripheral nerve sheath tumors occurring either de novo or arising from pre-existing tumors (e.g. neurofibromas, schwannomas etc.). Approximately half of such tumors are seen in individuals with neurofibromatosis type I (NF1), in such cases arising from pre-existing neurofibromas. […] Diagnostic criteria according to the WHO classification of soft tissue and bone tumors (5th edition): essential: sarcoma arising from a nerve or pre-existing nerve sheath tumor or in an NF1 patient. […] Imaging criteria are generally considered unreliable in differentiating from a more benign neurofibroma or schwannoma and there are no features to differentiate MPNST from other sarcomas. However, general rules favoring an MPNST include: the larger the lesion, the more likely for it to be malignant; irregular borders (although most MPNSTs can have well-defined margins); rapid growth in interval imaging. […] MPNST are aggressive tumors that carry a poor prognosis, with 20-25% of patients developing metastases. Overall 5-year survival for sporadic tumors is 65%. Poor prognostic factors include NF1, large size, location on the trunk, high-grade histological features.

• #1 Malignant Peripheral Nerve Sheath Tumors: Latest Concepts in Disease Pathogenesis and Clinical Management

  https://www.mdpi.com/2072-6694/15/4/1077

  The NCCN guidelines recommend using PET/CT for MPNST diagnosis, as MPNST usually results in a significant increase in 18F-FDG uptake. PET/CT is a well-studied technique that is thought to be more sensitive than conventional MRI; however, its diagnostic cutoff value is debatable. It is mainly believed that there is no possibility of malignancy when the standard uptake value (SUV) is less than 2.5, and MPNST should be addressed when the maximum standard uptake value (SUVmax) is greater than 3.5. However, some other studies suggest that SUVmax values greater than 4.0 or 6.1 have a higher specificity in MPNST diagnosis. Considering the poor prognosis of MPNST, the SUVmax cutoff of 3.5 is still commonly used. PET-guided biopsies provide a higher diagnostic value for tumors with intermediate SUVmax (2.5–3.5) and higher detection sensitivity. PET/CT can also detect metastasis in real-time, which is of great significance for the classification and prognosis of MPNST. It is worth noting that PET/CT and MRI serve complementary roles. However, there have been few studies on the effects of combining PET/CT and MRI, and only a few institutions are equipped to perform PET/MR; thus, additional research is needed.

• #1 Diagnosis and management of malignant peripheral nerve sheath tumors: Current practice and future perspectives

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7317062/

  The use of WB-MRI has allowed us to follow the natural course of PN development over time, which has expanded our understanding of the progression of PN to MPNST. […] Despite these advances, MRI is still unable to reliably differentiate between benign and malignant tumors. […] Numerous reports have suggested that FDG-PET is more sensitive in the detection of MPNST, and has more significant utility for making a diagnosis than MRI, with sensitivities nearing 90%. […] In contrast to some soft tissue sarcomas, there is no pathognomonic genetic alteration or immunohistochemical stain to diagnose MPNST. […] Given the lack of specific morphological criteria or immunohistochemical/molecular tests, it can be difficult to distinguish MPNST from other sarcomas. […] While this testing may be useful to identify and characterize these tumors, there is no standardized set of immunohistochemical markers that have been applied across clinical laboratories to diagnose MPNST. […] Given the lack of specific pathologic diagnostic criteria, the field would benefit from identification of more accurate biomarkers for this disease. […] The decision to pursue a biopsy versus upfront resection of a suspected MPNST is another area of controversy.

• #1

  https://link.springer.com/article/10.1007/s40336-024-00669-6

  Malignant peripheral nerve sheath tumors (MPNSTs) are rare tumors that show high metastatic potential and have a poor prognosis. [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) is helpful for diagnosing MPNSTs, but the ideal parameters and threshold values remain unclear. The purpose of our study was to evaluate visual assessment and quantitative analysis of [18F]FDG PET/CT for differentiating between benign peripheral nerve sheath tumors (BPNSTs) and MPNSTs. […] Among the visual parameters, uptake intensity greater than liver (P=0.001) and heterogenous uptake (P=0.004) were significant parameters for diagnosing MPNSTs. All of the quantitative parameters analysed were significant for diagnosing MPNSTs, with SUVmax showing the largest area under the curve (AUC) of 0.87 (P0.001) with an optimal threshold of 6.9 (sensitivity 76.8% and specificity 87.2%). In addition, the SUVmax of high-grade MPNSTs were significantly higher than those of low-grade MPNSTs (P=0.039). […] Of the [18F]FDG PET/CT measures investigated, SUVmax showed the highest accuracy for diagnosing MPNSTs, and also showed an association with the grade of MPNSTs.

• #1 Malignant peripheral nerve sheath tumour (MPNST) | Czarnecka | Oncology in Clinical Practice

  https://journals.viamedica.pl/oncology_in_clinical_practice/article/view/60061

  Pathology of peripheral nerve sheath tumors: diagnostic overview and update on selected diagnostic problems. […] The cytopathology of malignant peripheral nerve sheath tumor: a report of 55 fine-needle aspiration cases. […] Comparative effectiveness of 18F-FDG PET/CT versus whole-body MRI for detection of malignant peripheral nerve sheath tumors in neurofibromatosis type 1. […] [18F]2-fluoro-2-deoxy-D-glucose positron emission tomography (FDG PET) as a diagnostic tool for neurofibromatosis 1 (NF1) associated malignant peripheral nerve sheath tumours (MPNSTs): a long-term clinical study. […] 18F-FDG PET/CT for detection of malignant peripheral nerve sheath tumours in neurofibromatosis type 1: tumour-to-liver ratio is superior to an SUVmax cut-off. […] Guidelines for the diagnosis and management of individuals with neurofibromatosis 1.

• #1

  https://journals.lww.com/md-journal/fulltext/2019/03290/neurofibromatosis_type_i_with_malignant_peripheral.49.aspx

  In the current case, the radiological characteristics could not yield a definitive diagnosis of malignant peripheral nerve sheath tumor; however, the large size and irregular shape of the tumor, involvement of a large nerve trunk, abundant intratumoral feeding arteries, and intratumoral calcifications supported the diagnosis. […] Currently, the standard treatment regimen for malignant peripheral nerve sheath tumor is extensive surgical resection. […] Moreover, postoperative adjuvant radiotherapy can help control local recurrence and improve the 5-year survival rate. […] Malignant peripheral nerve sheath tumor in NF1 is an extremely rare entity that is challenging to diagnose. High-frequency ultrasound can facilitate the identification of intratumoral vessels and suggest the diagnosis of malignant peripheral nerve sheath tumor.

• #1 Malignant Peripheral Nerve Sheath Tumors—A Comprehensive Review of Pathophysiology, Diagnosis, and Multidisciplinary Management

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8774267/

  In most series, patients with either a diagnosis of NF1 or prior radiotherapy have shown a worse overall survival compared to those with sporadic MPNSTs likely due to the greater propensity towards metastases and/or local invasion demonstrated by tumors in these patients. […] The survival gap does appear to be narrowing, however, with patients with NF1-related MPNSTs faring better in studies performed more recently though still not as well as those with sporadic MPNSTs. […] Imaging studies are necessary to delineate tumor extent and may also be of some use in differentiating MPNSTs versus plexiform neurofibromas. […] Definitive diagnosis of an MPNST requires histologic examination. […] A biopsy specimen may be insufficient to characterize the tumor adequately, and resection is preferred where possible.

• #1 Diagnosis, Treatment and Survival of 65 Patients with Malignant Peripheral Nerve Sheath Tumors | Anticancer Research

  https://ar.iiarjournals.org/content/34/2/777

  Background: Malignant peripheral nerve sheath tumors (MPNST) account for up to 10% of all malignant soft tissue tumors in adults. Insufficient data are available on diagnosis, differential diagnosis and treatment modalities as well as prognosis. […] Histopathological diagnosis of MPNST may be difficult, since there is a variety of differential diagnoses. As the tumor is rare, re-classification may be necessary in terms of special tertiary reference centers. […] The diagnosis should begin with a complete medical and family history and a physical examination, focusing on the skin and neurology. The most important known risk factor for MPNST development is NF1, in which 10% of patients develop an MPNST during their lifetime. […] After imaging (magnetic resonance imaging or computer tomography with contrast medium) a biopsy should be performed. In our experience, open biopsies result in superior histological evaluation because more tissue is gathered which is more representative especially for inhomogeneous tumors.

• #1 Diagnostic Accuracy of PET/CT-Guided Percutaneous Biopsies for Malignant Peripheral Nerve Sheath Tumors in Neurofibromatosis Type 1 Patients | PLOS One

  https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0138386

  PET/CT-guided percutaneous biopsies are an effective and relatively non-traumatic procedure for diagnosis of NF1-related MPNST. It is the most reliable approach for early detection of MPNST. […] We conducted the present study to evaluate the diagnostic accuracy, suitability, and complications associated with PET/CT-guided percutaneous biopsies for the diagnosis of NF1-related MPNST. […] The current method using PET/CT-guided percutaneous biopsies is the best approach for an NF1-related MPNST diagnosis and for assessing the type of surgery necessary for treatment. […] This diagnosis strategy provided only a single false negative (BPNST with atypical cells on the biopsy and MPNST on the resected tumor). […] In conclusion, PET/CT-guided percutaneous biopsies provide a rapid, relatively non-traumatic, and effective procedure for diagnosing NF1-related MPNST. This combination is the most reliable approach for early detection of MPNST, reducing the need for more invasive surgical procedures.

• #1 Clinicopathological and Therapeutic Challenge: A Case Report of a Malignant Peripheral Nerve Sheath Tumor – Turkish Journal of Dermatology

  https://turkjdermatol.com/articles/clinicopathological-and-therapeutic-challenge-a-case-report-of-a-malignant-peripheral-nerve-sheath-tumor/doi/tjd.galenos.2024.18209

  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. […] Diagnosis primarily relies on histopathological examination, which typically reveals spindle cell neoplastic proliferation with varying cell densities and patterns, such as storiform or whorled arrangements. Immunohistochemical markers frequently used to support diagnosis include S100, SOX10, and CD34, although their expression can overlap with that of other soft tissue tumors, thereby complicating the diagnosis. […] Histopathological findings of spindle cell proliferation and immunohistochemical positivity for S100 and SOX10 were crucial for diagnosis. The absence of HMB45 and Melan-A indicated no melanocytic differentiation, which helps exclude melanoma and supports the diagnosis of MPNST by focusing on its neuroectodermal origin.

• #1 Malignant Peripheral Nerve Sheath Tumor

  https://www.webpathology.com/images/soft-tissue/peripheral-nerve/malignant-peripheral-nerve-sheath-tumor

  Malignant peripheral nerve sheath tumors (MPNST) are a group of high-grade sarcomas that show differentiation along one of the nerve sheath elements such as Schwann cell, perineural cell, and fibroblast. They make up 5% to 10% of all soft tissue sarcomas. The diagnosis of MPNST is made if a fibrosarcomatous-appearing tumor: 1) obviously arises from a peripheral nerve; or 2) the tumor arises from a preexisting neurofibroma in NF1; or 3) the tumor has histologic features of a malignant Schwann cell tumor – including hyper- and hypocellular areas, irregular wavy hyperchromatic nuclei with tapered ends, whorled structures, epithelioid appearance of perivascular tumor cells, and immunohistochemical or ultrastructural evidence of Schwann cell differentiation. The diagnosis of MPNST is favored by positivity for S-100, nestin, HMGA2, and SOX10. MPNSTs are high-grade sarcomas with a tendency to local recurrences (about 40% of cases) as well as distant metastases (40% to 60% of cases) after resection. […] The differential diagnosis of MPNST includes fibrosarcoma, monophasic synovial sarcoma, leiomyosarcoma, desmoplastic melanoma, as well as neurofibromas with atypical features.

• #1 Malignant Peripheral Nerve Sheath Tumour – SFA

  https://curesarcoma.org/sarcoma-subtypes/malignant-peripheral-nerve-sheath-tumour/

  Recently, diagnostic criteria to distinguish these tumors from other types of NF1-associated nerve sheath tumors have been established. […] Essential: sarcoma arising from a nerve or pre-existing nerve sheath tumor or in a patient with NF1; tumors with a spindle fascicular growth, geographical necrosis, and often a limited degree of nuclear pleomorphism; in the sporadic setting, diagnosis is most often based on the identification of Schwann cell differentiation (S100/SOX10 focal positivity) and/or loss of H3K27me3 expression in a soft tissue mass; heterologous elements in a sarcoma should suggest MPNST; epithelioid MPNSTs occur outside the NF1 setting and often show diffuse S100 and SOX10 positivity and loss of SMARCB1 expression.

• #1 Significance of H3K27me3 loss in the diagnosis of malignant peripheral nerve sheath tumors | Modern Pathology

  https://www.nature.com/articles/modpathol201797

  The diagnosis of malignant peripheral nerve sheath tumors can be challenging and other spindle cell sarcomas commonly enter in the differential diagnosis. […] Loss of trimethylation at lysine 27 of histone-H3 (H3K27me3) by immunohistochemistry was recently described in malignant peripheral nerve sheath tumors. […] Complete H3K27me3 loss is a moderately sensitive and relatively specific marker for the diagnosis of malignant peripheral nerve sheath tumor when the differential diagnosis includes synovial sarcoma and fibrosarcomatous dermatofibrosarcoma protuberans. […] The main aim of the present study is to evaluate H3K27me3 staining pattern in malignant peripheral nerve sheath tumor, synovial sarcoma and fibrosarcomatous dermatofibrosarcoma protuberans diagnosed in our institution and assess its utility in this differential diagnosis.

• #1 MPNST : Differential Diagnosis

  https://www.webpathology.com/images/soft-tissue/peripheral-nerve/malignant-peripheral-nerve-sheath-tumor/44877

  The differential diagnosis of a malignant peripheral nerve sheath tumor includes fibrosarcoma, monophasic synovial sarcoma, leiomyosarcoma, desmoplastic melanoma, as well as neurofibroma with atypical features. […] The diagnosis of MPNST is made if a fibrosarcomatous-appearing tumor: 1) obviously arises from a peripheral nerve; or 2) the tumor arises from a preexisting neurofibroma in NF1; or 3) the tumor has histologic features of a malignant Schwann cell tumor – including hyper- and hypocellular areas, irregular wavy hyperchromatic nuclei with tapered ends, whorled structures, epithelioid appearance of perivascular tumor cells, and immunohistochemical or ultrastructural evidence of Schwann cell differentiation. […] The diagnosis of MPNST is favored by positivity for S-100, nestin, HMGA2, and SOX10.

• #1 Malignant Peripheral Nerve Sheath Tumors: Differentiation Patterns and Immunohistochemical Features – A Mini-Review and Our New Findings

  https://www.jcancer.org/v03p0303.htm

  Malignant peripheral nerve sheath tumors (MPNST) represent a group of highly heterogeneous human malignancies often with multiple histological origins, divergent differentiation patterns, and diverse immunohistochemical presentations. The differential diagnosis of MPNST from other spindle cell neoplasms poses great challenges for pathologists. […] The diagnosis of MPNST with multiple mesenchymal differentiations is difficult, and sometimes should be differentiated from rhabdomyosarcoma, osteosarcoma, chondrosarcoma or liposarcoma. […] Additionally, MPNST with glandular differentiation must be differentiated from metastatic carcinoma. […] MPNST is a tumor associated with an aggressive behavior and its prognosis is poor with death occurring in 63%, usually with 2-year of diagnosis. […] The 2-year and 5-year overall survival rate are reported to be 57% and 39%, with the median survival period is 32 months.

• #1 Malignant Peripheral Nerve Sheath Tumors—A Comprehensive Review of Pathophysiology, Diagnosis, and Multidisciplinary Management

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8774267/

  Given MPNSTs locally aggressive nature and tendency to metastasize, multidisciplinary, multi-modality management is frequently a feature of many patients treatment courses. […] The MPNST treatment philosophy can therefore be summarized as thus: maximal surgical resection, potentially in combination with neoadjuvant chemotherapy or radiotherapy to render an initially inoperable tumor operable, followed by adjuvant chemotherapy or radiotherapy when the margins of resection are positive or metastatic disease exists.

• #1 A detailed landscape of genomic alterations in malignant peripheral nerve sheath tumor cell lines challenges the current MPNST diagnosis | bioRxiv

  https://www.biorxiv.org/content/10.1101/2022.05.07.491026.full

  Malignant peripheral nerve sheath tumors (MPNSTs) are soft tissue sarcomas that arise from the peripheral nervous system. The diagnosis of MPNSTs can be challenging, especially outside of the NF1 context since specific histological criteria have not been completely established. […] Genomic analysis may both facilitate differential diagnoses and suggest precision medicine strategies. […] MPNSTs are usually high-grade malignant spindle cell neoplasms arising in association with large peripheral nerves. Their diagnosis can be challenging, especially outside of individuals with NF1, since MPNSTs are rare tumors and specific histological criteria have not been completely established. […] Established cell lines are an important tool for gaining insight into cancer biology and treatment. However, there are also different caveats in their use as faithful and useful models, with issues including misidentification and cross-contamination and poor characterization of similarity to their tumor source.

• #1 Malignant Peripheral Nerve Sheath Tumors—A Comprehensive Review of Pathophysiology, Diagnosis, and Multidisciplinary Management

  https://www.mdpi.com/2227-9067/9/1/38

  MPNSTS are most often characterized by the second variety of mutations—specifically by loss of function of the tumor suppressor gene NF1. […] Although bi-allelic NF1 inactivation or mutation appears necessary for MPNST development, it does not seem sufficient. […] Therefore, one potential model for MPNST development proposes that bi-allelic NF1 loss occurs in nerve-sheath precursor cells, resulting in benign neurofibroma formation. […] Patients with MPNSTs were eligible for inclusion in the recently reported COG ARST0332 trial. […] Given MPNSTs’ locally aggressive nature and tendency to metastasize, multidisciplinary, multi-modality management is frequently a feature of many patients’ treatment courses. […] The MPNST treatment philosophy can therefore be summarized as thus: maximal surgical resection, potentially in combination with neoadjuvant chemotherapy or radiotherapy to render an initially inoperable tumor operable, followed by adjuvant chemotherapy or radiotherapy when the margins of resection are positive or metastatic disease exists.

• #1 A detailed landscape of genomic alterations in malignant peripheral nerve sheath tumor cell lines challenges the current MPNST diagnosis | bioRxiv

  https://www.biorxiv.org/content/10.1101/2022.05.07.491026.full

  Genomic analysis such as copy number profiles, structural variants, mutation frequencies and signatures, presence of gain-of-function mutations, and the inactivation of specific TSGs, together with methylome-based sarcoma classification and cell identity marker analysis, emerge as valuable tools for a better differential diagnosis and classification of MPNSTs.

• #1 Malignant Peripheral Nerve Sheath Tumor (MPNST)

  https://my.clevelandclinic.org/health/diseases/malignant-peripheral-nerve-sheath-tumor-mpnst

  A malignant peripheral nerve sheath tumor (MPNST) is a very rare type of soft tissue sarcoma. […] How is a malignant peripheral nerve sheath tumor diagnosed? […] A healthcare provider will perform a physical exam and assess your overall health. This includes a review of your medical history, family history and symptoms. They may do: […] Providers may do magnetic resonance imaging (MRI) and positron emission tomography (PET) scans. […] Providers may do a biopsy to obtain tissue for a medical pathologist to examine under a microscope. […] If you have a malignant peripheral nerve sheath tumor, your provider may recommend you and close family members have genetic tests to find out if you or they have neurofibromatosis type 1 (NF1) or neurofibromatosis type 2 (schwannomatosis), another type of nerve sheath tumor.

• #1 Malignant Peripheral Nerve Sheath Tumors—A Comprehensive Review of Pathophysiology, Diagnosis, and Multidisciplinary Management

  https://www.mdpi.com/2227-9067/9/1/38

  Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive soft tissue sarcomas (STS) with nerve sheath differentiation and a tendency to metastasize. […] The staging of MPNSTs is complicated and requires close multi-disciplinary collaboration. […] Their primary management is most often surgical in nature, with non-surgical modalities playing a supportive, necessary role, particularly in metastatic, invasive, or widespread disease. […] We, therefore, sought to provide a comprehensive review of the relevant literature describing the characteristics of these tumors, their pathophysiology and risk factors, their diagnosis, and their multi-disciplinary treatment. […] Advances in the molecular characterization of these tumors have also begun to allow the integration of targeted RAS/RAF/MEK/ERK pathway inhibitors into MPNST management.

• #1 Malignant Peripheral Nerve Sheath Tumor (MPNST)

  https://my.clevelandclinic.org/health/diseases/malignant-peripheral-nerve-sheath-tumor-mpnst

  Healthcare providers typically do surgery to remove a malignant peripheral nerve sheath tumor. […] Providers may treat MPNST by combining surgery and chemotherapy or radiation therapy. […] Researchers are studying immunotherapy or targeted therapy as potential new or additional treatments. […] Your prognosis is what your healthcare team believes will happen after you finish treatment. […] The prognosis for people with NF1 who have these tumors is less positive than the prognosis for people who dont have NF1. […] Pathologists classify tumors as being high-grade or low-grade, based on how cells appear when viewed under a microscope. […] MPNSTs may grow up to 10 centimeters. […] Tumors that spread from where they started are more difficult to treat. […] Survival rates are estimates based on other peoples experiences with malignant peripheral nerve sheath tumors. […] According to the National Cancer Institute (U.S.), 23% to 69% of people with MPNST were alive five years after they were diagnosed.

• #1 Malignant peripheral nerve sheath tumors and neurofibromatosis 1

  https://www.hcplive.com/view/2008-01_02_

  Adjuvant radiotherapy is indicated for intermediate-to high-grade lesions and low-grade MPNSTs following a marginal excision. […] Chemotherapy for MPNSTs is usually reserved to treat metastatic disease. […] Primary prognostic indicators include tumor size (prognosis is worse if the tumor exceeds 5 cm), tumor grade (grade 1 is best, grade 3 is worst), and positive surgical margins (poor prognosis). […] Even after surgical excision and radiation therapy for local control, patients with intermediate- or high-grade tumors are at high risk of developing metastatic disease. […] The future in treating MPNSTs revolves around improving our understanding of the disease’s molecular biology and developing molecular-based therapies. […] Although MPNSTs are rare, they remain a common and serious disease among patients with NF1.

• #1 Malignant Peripheral Nerve Sheath Tumors—A Comprehensive Review of Pathophysiology, Diagnosis, and Multidisciplinary Management

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8774267/

  Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive soft tissue sarcomas (STS) with nerve sheath differentiation and a tendency to metastasize. […] The staging of MPNSTs is complicated and requires close multi-disciplinary collaboration. […] Their primary management is most often surgical in nature, with non-surgical modalities playing a supportive, necessary role, particularly in metastatic, invasive, or widespread disease. […] A close partnership between surgical and medical oncologists is therefore necessary. […] Advances in the molecular characterization of these tumors have also begun to allow the integration of targeted RAS/RAF/MEK/ERK pathway inhibitors into MPNST management. […] MPNSTs may arise de novo from a peripheral nerve OR as a malignant transformation of a pre-existing benign nerve sheath tumor especially neurofibromas.

• #1 Peripheral nerve tumors – Diagnosis and treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/peripheral-nerve-tumors/diagnosis-treatment/drc-20355075

  To diagnose a peripheral nerve tumor, your health care provider will ask about your symptoms and medical history. You may undergo a general physical exam and a neurological exam. Several tests may help pinpoint the cause of your symptoms. […] A tumor biopsy. If you have a nerve tumor, you may need a biopsy. A small sample of cells from the tumor is removed and analyzed. Depending on the tumor’s size and location, you may need to have medicine that numbs an area of the body, called local anesthesia, or medicine that puts you to sleep, called general anesthesia, during the biopsy. Sometimes a biopsy is the only way to determine whether a tumor is cancerous. […] Peripheral nerve tumors aren’t common. It’s important to find a provider who is experienced in diagnosing and treating them. If needed, seek a second opinion. […] Cancerous tumors are treated with standard cancer therapies. These include surgery, chemotherapy and radiation therapy. Early diagnosis and treatment are the most important factors for a good outcome. Tumors may come back after treatment.

• #2 Malignant Peripheral Nerve Sheath Tumors—A Comprehensive Review of Pathophysiology, Diagnosis, and Multidisciplinary Management

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8774267/

  Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive soft tissue sarcomas (STS) with nerve sheath differentiation and a tendency to metastasize. […] The staging of MPNSTs is complicated and requires close multi-disciplinary collaboration. […] Their primary management is most often surgical in nature, with non-surgical modalities playing a supportive, necessary role, particularly in metastatic, invasive, or widespread disease. […] A close partnership between surgical and medical oncologists is therefore necessary. […] Advances in the molecular characterization of these tumors have also begun to allow the integration of targeted RAS/RAF/MEK/ERK pathway inhibitors into MPNST management. […] MPNSTs may arise de novo from a peripheral nerve OR as a malignant transformation of a pre-existing benign nerve sheath tumor especially neurofibromas.

• #2 Diagnosis, Treatment and Survival of 65 Patients with Malignant Peripheral Nerve Sheath Tumors | Anticancer Research

  https://ar.iiarjournals.org/content/34/2/777

  Background: Malignant peripheral nerve sheath tumors (MPNST) account for up to 10% of all malignant soft tissue tumors in adults. Insufficient data are available on diagnosis, differential diagnosis and treatment modalities as well as prognosis. […] Histopathological diagnosis of MPNST may be difficult, since there is a variety of differential diagnoses. As the tumor is rare, re-classification may be necessary in terms of special tertiary reference centers. […] The diagnosis should begin with a complete medical and family history and a physical examination, focusing on the skin and neurology. The most important known risk factor for MPNST development is NF1, in which 10% of patients develop an MPNST during their lifetime. […] After imaging (magnetic resonance imaging or computer tomography with contrast medium) a biopsy should be performed. In our experience, open biopsies result in superior histological evaluation because more tissue is gathered which is more representative especially for inhomogeneous tumors.

• #2 Malignant peripheral nerve sheath tumors | Beacon Health System

  https://www.beaconhealthsystem.org/library/diseases-and-conditions/malignant-peripheral-nerve-sheath-tumors?content_id=CON-20313998

  Malignant peripheral nerve sheath tumors are rare cancers that start in the lining of the nerves. […] Tests and procedures used to diagnose malignant peripheral nerve sheath tumors include: […] A detailed exam of the nervous system, known as a neurological exam, helps a health care provider gather clues for diagnosis. […] Imaging tests make pictures of the body. The pictures might help providers see the size of the cancer and whether it has spread to other parts of the body. […] A biopsy is a procedure to remove a sample of tissue for testing in a lab. The sample is tested in a lab to see if it is cancer. Other special tests give more details about the cancer cells. The health care team uses this information to make a treatment plan.

• #2 Malignant peripheral nerve sheath tumor | Radiology Reference Article | Radiopaedia.org

  https://radiopaedia.org/articles/malignant-peripheral-nerve-sheath-tumour?lang=us

  Malignant peripheral nerve sheath tumors (MPNSTs) are forms of peripheral nerve sheath tumors occurring either de novo or arising from pre-existing tumors (e.g. neurofibromas, schwannomas etc.). Approximately half of such tumors are seen in individuals with neurofibromatosis type I (NF1), in such cases arising from pre-existing neurofibromas. […] Diagnostic criteria according to the WHO classification of soft tissue and bone tumors (5th edition): essential: sarcoma arising from a nerve or pre-existing nerve sheath tumor or in an NF1 patient. […] Imaging criteria are generally considered unreliable in differentiating from a more benign neurofibroma or schwannoma and there are no features to differentiate MPNST from other sarcomas. However, general rules favoring an MPNST include: the larger the lesion, the more likely for it to be malignant; irregular borders (although most MPNSTs can have well-defined margins); rapid growth in interval imaging. […] MPNST are aggressive tumors that carry a poor prognosis, with 20-25% of patients developing metastases. Overall 5-year survival for sporadic tumors is 65%. Poor prognostic factors include NF1, large size, location on the trunk, high-grade histological features.

• #2 Diagnosis and management of malignant peripheral nerve sheath tumors: Current practice and future perspectives

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7317062/

  The use of WB-MRI has allowed us to follow the natural course of PN development over time, which has expanded our understanding of the progression of PN to MPNST. […] Despite these advances, MRI is still unable to reliably differentiate between benign and malignant tumors. […] Numerous reports have suggested that FDG-PET is more sensitive in the detection of MPNST, and has more significant utility for making a diagnosis than MRI, with sensitivities nearing 90%. […] In contrast to some soft tissue sarcomas, there is no pathognomonic genetic alteration or immunohistochemical stain to diagnose MPNST. […] Given the lack of specific morphological criteria or immunohistochemical/molecular tests, it can be difficult to distinguish MPNST from other sarcomas. […] While this testing may be useful to identify and characterize these tumors, there is no standardized set of immunohistochemical markers that have been applied across clinical laboratories to diagnose MPNST. […] Given the lack of specific pathologic diagnostic criteria, the field would benefit from identification of more accurate biomarkers for this disease. […] The decision to pursue a biopsy versus upfront resection of a suspected MPNST is another area of controversy.

• #2

  https://link.springer.com/article/10.1007/s40336-024-00669-6

  Malignant peripheral nerve sheath tumors (MPNSTs) are rare tumors that show high metastatic potential and have a poor prognosis. [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) is helpful for diagnosing MPNSTs, but the ideal parameters and threshold values remain unclear. The purpose of our study was to evaluate visual assessment and quantitative analysis of [18F]FDG PET/CT for differentiating between benign peripheral nerve sheath tumors (BPNSTs) and MPNSTs. […] Among the visual parameters, uptake intensity greater than liver (P=0.001) and heterogenous uptake (P=0.004) were significant parameters for diagnosing MPNSTs. All of the quantitative parameters analysed were significant for diagnosing MPNSTs, with SUVmax showing the largest area under the curve (AUC) of 0.87 (P0.001) with an optimal threshold of 6.9 (sensitivity 76.8% and specificity 87.2%). In addition, the SUVmax of high-grade MPNSTs were significantly higher than those of low-grade MPNSTs (P=0.039). […] Of the [18F]FDG PET/CT measures investigated, SUVmax showed the highest accuracy for diagnosing MPNSTs, and also showed an association with the grade of MPNSTs.

• #2 Diagnostic Accuracy of PET/CT-Guided Percutaneous Biopsies for Malignant Peripheral Nerve Sheath Tumors in Neurofibromatosis Type 1 Patients | PLOS One

  https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0138386

  Malignant peripheral nerve sheath tumors (MPNST) are one of the most frequent causes of death in patients with neurofibromatosis type 1 (NF1). Early detection is crucial because complete surgical resection is the only curative treatment. […] The objective of the present work was to investigate the effectiveness of and complications associated with PET/CT-guided percutaneous biopsies for an NF1-related MPNST diagnosis. […] The first PET/CT-guided percutaneous biopsies enabled a pathological diagnosis for all of the patients (no „inconclusive” results were obtained), and no secondary procedures were needed. […] The PET/CT-guided percutaneous biopsy gave 25 accurate diagnoses and one false negative (BPNST with atypical cells on the biopsy and MPNST on the operated tumor), resulting in a diagnostic accuracy rate of 96%.

• #2 Malignant Peripheral Nerve Sheath Tumour – SFA

  https://curesarcoma.org/sarcoma-subtypes/malignant-peripheral-nerve-sheath-tumour/

  Recently, diagnostic criteria to distinguish these tumors from other types of NF1-associated nerve sheath tumors have been established. […] Essential: sarcoma arising from a nerve or pre-existing nerve sheath tumor or in a patient with NF1; tumors with a spindle fascicular growth, geographical necrosis, and often a limited degree of nuclear pleomorphism; in the sporadic setting, diagnosis is most often based on the identification of Schwann cell differentiation (S100/SOX10 focal positivity) and/or loss of H3K27me3 expression in a soft tissue mass; heterologous elements in a sarcoma should suggest MPNST; epithelioid MPNSTs occur outside the NF1 setting and often show diffuse S100 and SOX10 positivity and loss of SMARCB1 expression.

• #2 MPNST : Differential Diagnosis

  https://www.webpathology.com/images/soft-tissue/peripheral-nerve/malignant-peripheral-nerve-sheath-tumor/44877

  The differential diagnosis of a malignant peripheral nerve sheath tumor includes fibrosarcoma, monophasic synovial sarcoma, leiomyosarcoma, desmoplastic melanoma, as well as neurofibroma with atypical features. […] The diagnosis of MPNST is made if a fibrosarcomatous-appearing tumor: 1) obviously arises from a peripheral nerve; or 2) the tumor arises from a preexisting neurofibroma in NF1; or 3) the tumor has histologic features of a malignant Schwann cell tumor – including hyper- and hypocellular areas, irregular wavy hyperchromatic nuclei with tapered ends, whorled structures, epithelioid appearance of perivascular tumor cells, and immunohistochemical or ultrastructural evidence of Schwann cell differentiation. […] The diagnosis of MPNST is favored by positivity for S-100, nestin, HMGA2, and SOX10.

• #2 Significance of H3K27me3 loss in the diagnosis of malignant peripheral nerve sheath tumors | Modern Pathology

  https://www.nature.com/articles/modpathol201797

  The diagnosis of malignant peripheral nerve sheath tumors can be challenging and other spindle cell sarcomas commonly enter in the differential diagnosis. […] Loss of trimethylation at lysine 27 of histone-H3 (H3K27me3) by immunohistochemistry was recently described in malignant peripheral nerve sheath tumors. […] Complete H3K27me3 loss is a moderately sensitive and relatively specific marker for the diagnosis of malignant peripheral nerve sheath tumor when the differential diagnosis includes synovial sarcoma and fibrosarcomatous dermatofibrosarcoma protuberans. […] The main aim of the present study is to evaluate H3K27me3 staining pattern in malignant peripheral nerve sheath tumor, synovial sarcoma and fibrosarcomatous dermatofibrosarcoma protuberans diagnosed in our institution and assess its utility in this differential diagnosis.

• #2 Significance of H3K27me3 loss in the diagnosis of malignant peripheral nerve sheath tumors | Modern Pathology

  https://www.nature.com/articles/modpathol201797

  Using the negativepositive scoring system, the sensitivity and specificity of H3K27me3 loss for the diagnosis of malignant peripheral nerve sheath tumor versus synovial sarcoma was 44% and 92%, respectively. […] Among malignant peripheral nerve sheath tumors, complete loss of H3K27me3 expression (score 0) was not associated with gender, tumor site, or tumor size. […] In summary, complete loss of H3K27me3 immunostaining can be a useful tool in the diagnosis of malignant peripheral nerve sheath tumor in this differential diagnosis setting since it offers moderate sensitivity and relatively high specificity.

• #2 Malignant Peripheral Nerve Sheath Tumors—A Comprehensive Review of Pathophysiology, Diagnosis, and Multidisciplinary Management

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8774267/

  Given MPNSTs locally aggressive nature and tendency to metastasize, multidisciplinary, multi-modality management is frequently a feature of many patients treatment courses. […] The MPNST treatment philosophy can therefore be summarized as thus: maximal surgical resection, potentially in combination with neoadjuvant chemotherapy or radiotherapy to render an initially inoperable tumor operable, followed by adjuvant chemotherapy or radiotherapy when the margins of resection are positive or metastatic disease exists.

• #2 A Discussion of Malignant Peripheral Nerve Sheath Tumors (MPNSTs) – Neurofibromatosis Program

  https://www.uab.edu/medicine/nfprogram/blog/a-discussion-of-malignant-peripheral-nerve-sheath-tumors-mpnsts

  Based on these results, a positron emission tomography (PET) scan with radiographic computed tomography (PET-CT) or magnetic resonance imaging (PET-MRI) may be performed to determine the tumors uptake of radioactive tracer material. […] Malignant tumors take up more of the radioactive material on the scan, indicating a possible malignancy. […] Either a needle or surgical biopsy then needs to be performed for pathological confirmation of a malignancy. […] Current NF clinical trials are evaluating chemotherapy as well as other therapeutics targeting genetic changes in the tumor. […] In conclusion, because MPNSTs are difficult to treat, early detection is critically important.

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