{"entity":{"id":"malignant-peripheral-nerve-sheath-tumour","kind":"cancer","name":"Malignant peripheral nerve sheath tumour (MPNST)","aka":["MPNST","Neurofibrosarcoma (historic)","Malignant schwannoma (historic)"],"tldr":"Malignant peripheral nerve sheath tumour is a sarcoma that grows from the covering of a nerve, most often in people with neurofibromatosis type 1 when a benign plexiform neurofibroma turns malignant. Surgery with radiotherapy is the only cure; chemotherapy with doxorubicin and ifosfamide shrinks some tumours, and drugs targeting the tumour's lost NF1 and PRC2 brakes are in trials.","summary":"Malignant peripheral nerve sheath tumour arises from Schwann cell lineage in a peripheral nerve or a pre-existing neurofibroma, sporadically, after radiotherapy or, in half of cases, in neurofibromatosis type 1, where atypical neurofibromatous neoplasms of uncertain biological potential are the recognised precursor. Its genome shows loss of NF1, then CDKN2A, then the polycomb repressive complex 2 components SUZ12 or EED, producing global loss of H3K27 trimethylation that pathologists now use as a diagnostic marker, alongside TP53 loss in high-grade tumours.\n\nTreatment of localised disease is wide resection with radiotherapy, which controls local disease but does not prevent metastasis; the tumours are large, deep and often involve major nerves and the spine, so margins are frequently compromised. Chemotherapy activity is modest: the SARC006 phase 2 trial of neoadjuvant doxorubicin-ifosfamide followed by ifosfamide-etoposide produced responses in a minority, more often in sporadic than NF1-associated tumours, and adjuvant chemotherapy is offered to fit patients with high-grade disease on the general sarcoma evidence.\n\nTargeted approaches follow the biology: MEK inhibitors such as selumetinib and mirdametinib, approved for the precursor plexiform neurofibromas, are being combined with mTOR inhibitors (SARC031) and other agents in MPNST; PRC2 loss confers sensitivity to some epigenetic and DNA-damaging strategies in models; and surveillance of people with neurofibromatosis by whole-body MRI and PET to catch transformation early is the most practical current advance.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Malignant_peripheral_nerve_sheath_tumor","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Malignant_peripheral_nerve_sheath_tumor"}],"tags":["subtype-page"],"related":["extremity-soft-tissue-sarcoma","desmoid-tumour"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"group":"sarcoma","burden":"About five percent of soft tissue sarcomas; half occur in people with neurofibromatosis type 1, whose lifetime risk is around one in ten, and it is the leading cause of death in that condition. Outcomes are poor, with five-year survival below half in most series.","subtypes":["NF1-associated MPNST (about half; arises in plexiform neurofibroma)","Sporadic MPNST","Radiation-associated MPNST","Epithelioid MPNST (SMARCB1 loss; not NF1-associated)","MPNST with heterologous differentiation (malignant Triton tumour)"],"biomarkers":["Loss of H3K27 trimethylation on immunohistochemistry (PRC2 loss)","NF1, CDKN2A, SUZ12 or EED alterations","TP53 loss (high grade)","FDG-PET uptake in neurofibromas (transformation)","Germline NF1 status"],"standardOfCare":[{"setting":"Localised","approach":"Wide resection with preoperative or postoperative radiotherapy; nerve sacrifice and reconstruction as needed; consider neoadjuvant or adjuvant anthracycline-ifosfamide for large high-grade tumours.","refs":["limb-salvage-surgery","imrt-igrt","doxorubicin","ifosfamide"]},{"setting":"Advanced","approach":"Doxorubicin plus ifosfamide (EORTC 62012), then ifosfamide-etoposide or trials; response rates lower in NF1-associated tumours.","refs":["doxorubicin","ifosfamide","eortc-62012","etoposide"]},{"setting":"Neurofibromatosis type 1 surveillance","approach":"Whole-body MRI and FDG-PET for growing or painful plexiform neurofibromas; biopsy of atypical lesions; MEK inhibitors for symptomatic plexiform neurofibromas.","refs":["mri","pet-ct","selumetinib","mirdametinib"]}],"stateOfArt":["H3K27me3 loss made a difficult diagnosis reproducible.","MEK inhibitors control the benign precursor but have not yet been proven in MPNST, where combinations with mTOR inhibitors are in trials.","Whole-body MRI surveillance in neurofibromatosis aims to catch transformation before it becomes incurable."],"history":[{"year":1990,"title":"NF1 gene cloned","refs":[]},{"year":2014,"title":"PRC2 (SUZ12, EED) loss found in most MPNST","refs":[]},{"year":2016,"title":"H3K27me3 loss adopted as a diagnostic marker","refs":[]},{"year":2017,"title":"SARC006: neoadjuvant chemotherapy responses in a minority, fewer in NF1-associated tumours","refs":["doxorubicin","ifosfamide"]},{"year":2020,"title":"Selumetinib approved for NF1 plexiform neurofibromas, the precursor lesion","refs":["selumetinib"]},{"year":2025,"title":"Mirdametinib approved for NF1 plexiform neurofibromas in adults and children","refs":["mirdametinib"]}],"pipeline":["selumetinib","mirdametinib","mek","ras-mapk"],"openProblems":["Metastasis is common even after complete local treatment.","Chemotherapy works less well in the NF1-associated tumours that make up half of cases.","No targeted drug has yet been proven in MPNST itself."],"parent":"sarcoma"},"route":"/cancers/malignant-peripheral-nerve-sheath-tumour/","neighbours":{"cancer":[{"id":"desmoid-tumour","kind":"cancer","name":"Desmoid tumour","route":"/cancers/desmoid-tumour/"},{"id":"sarcoma","kind":"cancer","name":"Sarcomas (soft tissue, bone, GIST)","route":"/cancers/sarcoma/"},{"id":"extremity-soft-tissue-sarcoma","kind":"cancer","name":"Soft tissue sarcoma of the extremity (localised and advanced)","route":"/cancers/extremity-soft-tissue-sarcoma/"}],"drug":[{"id":"doxorubicin","kind":"drug","name":"Doxorubicin","route":"/drugs/doxorubicin/"},{"id":"etoposide","kind":"drug","name":"Etoposide","route":"/drugs/etoposide/"},{"id":"ifosfamide","kind":"drug","name":"Ifosfamide","route":"/drugs/ifosfamide/"},{"id":"mirdametinib","kind":"drug","name":"Mirdametinib","route":"/drugs/mirdametinib/"},{"id":"selumetinib","kind":"drug","name":"Selumetinib","route":"/drugs/selumetinib/"}],"target":[{"id":"mek","kind":"target","name":"MEK1/2","route":"/targets/mek/"}],"pathway":[{"id":"ras-mapk","kind":"pathway","name":"RAS / RAF / MEK / ERK (MAPK)","route":"/pathways/ras-mapk/"}],"technology":[{"id":"imrt-igrt","kind":"technology","name":"IMRT / IGRT (modern external beam)","route":"/technologies/imrt-igrt/"},{"id":"limb-salvage-surgery","kind":"technology","name":"Limb-salvage surgery and endoprosthetic reconstruction","route":"/technologies/limb-salvage-surgery/"},{"id":"mri","kind":"technology","name":"MRI","route":"/technologies/mri/"},{"id":"pet-ct","kind":"technology","name":"PET/CT","route":"/technologies/pet-ct/"}],"trial":[{"id":"eortc-62012","kind":"trial","name":"EORTC 62012","route":"/trials/eortc-62012/"}]}}