# Malignant peripheral nerve sheath tumour (MPNST)

Source: https://onco.cc/cancers/malignant-peripheral-nerve-sheath-tumour/  
OnCo record `malignant-peripheral-nerve-sheath-tumour` (Cancer). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

Treatment 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.

Targeted 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.

## Fields

- Kind: Cancer
- Last checked: 2026-09-17
- Also known as: MPNST; Neurofibrosarcoma (historic); Malignant schwannoma (historic)
- Tags: subtype-page
- 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

## Sections of this record

The page is a hub with ten sections in reading order; large sections have their own page. The same plan as JSON: https://onco.cc/api/v1/cancers/malignant-peripheral-nerve-sheath-tumour/sections.json

- Overview (on the hub): The TL;DR, the family this cancer belongs to, the organ, who gets it and what the state of the art is. https://onco.cc/cancers/malignant-peripheral-nerve-sheath-tumour/#overview [3 state-of-the-art points]
- Types and stages (on the hub): Anatomy, the subtypes and how they differ, how it is staged, and where advanced disease spreads. https://onco.cc/cancers/malignant-peripheral-nerve-sheath-tumour/#what-it-is [5 subtypes]
- Symptoms and diagnosis (on the hub): How this cancer shows itself, how the diagnosis is confirmed, and the biomarkers clinicians test for. https://onco.cc/cancers/malignant-peripheral-nerve-sheath-tumour/#finding-it [5 biomarkers]
- Treatment (on the hub): The standard of care by setting, the medicines, surgery and radiotherapy named in it, and the regimens behind them. https://onco.cc/cancers/malignant-peripheral-nerve-sheath-tumour/#treating-it [3 settings, 3 decisions with options]
- Trials and papers (on the hub): Trials recruiting now, the landmark trials, the trials held by this cancer's subtypes, the key papers and what they mean, the latest literature, and the milestones year by year. https://onco.cc/cancers/malignant-peripheral-nerve-sheath-tumour/#evidence [1 trial, 4 key papers, 6 milestones]
- Biology and targets (on the hub): The molecular landscape: the targets and how often each appears, the pathways, the mechanics stages and the preclinical models. https://onco.cc/cancers/malignant-peripheral-nerve-sheath-tumour/#science [3 targets, 1 pathway]
- Countries and centres (own page): Cases by country, the UK and NHS pathway and other country lenses, the expert centres with trials on record, and the centres named on this cancer's subtypes. https://onco.cc/cancers/malignant-peripheral-nerve-sheath-tumour/where-you-are/
- Decisions and support (on the hub): The decisions you may face, the aids that walk through them, the warnings on record, the first sixty days and the questions to ask. https://onco.cc/cancers/malignant-peripheral-nerve-sheath-tumour/#living-with-it [16 questions, 6 red cards]
- Pipeline and open problems (own page): Everything in development, the medicines held by this cancer's subtypes, the open problems and what is being done about them, the roadmaps, and what changed on this record. https://onco.cc/cancers/malignant-peripheral-nerve-sheath-tumour/coming/ [5 medicines, 1 trial, 3 open problems]
- Data (own page): Every connected record, the notes, the JSON, Markdown and RDF twins, and where the record came from and when it was checked. https://onco.cc/cancers/malignant-peripheral-nerve-sheath-tumour/data/ [28 connected records]

## Standard of care

- Localised: Wide resection with preoperative or postoperative radiotherapy; nerve sacrifice and reconstruction as needed; consider neoadjuvant or adjuvant anthracycline-ifosfamide for large high-grade tumours. ([Limb-salvage surgery and endoprosthetic reconstruction](https://onco.cc/technologies/limb-salvage-surgery/), [IMRT / IGRT (modern external beam)](https://onco.cc/technologies/imrt-igrt/), [Doxorubicin](https://onco.cc/drugs/doxorubicin/), [Ifosfamide](https://onco.cc/drugs/ifosfamide/))
- Advanced: Doxorubicin plus ifosfamide (EORTC 62012), then ifosfamide-etoposide or trials; response rates lower in NF1-associated tumours. ([Doxorubicin](https://onco.cc/drugs/doxorubicin/), [Ifosfamide](https://onco.cc/drugs/ifosfamide/), [EORTC 62012](https://onco.cc/trials/eortc-62012/), [Etoposide](https://onco.cc/drugs/etoposide/))
- Neurofibromatosis type 1 surveillance: Whole-body MRI and FDG-PET for growing or painful plexiform neurofibromas; biopsy of atypical lesions; MEK inhibitors for symptomatic plexiform neurofibromas. ([MRI](https://onco.cc/technologies/mri/), [PET/CT](https://onco.cc/technologies/pet-ct/), [Selumetinib](https://onco.cc/drugs/selumetinib/), [Mirdametinib](https://onco.cc/drugs/mirdametinib/))

## State of the art

- 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.

## Open problems

- 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.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Malignant_peripheral_nerve_sheath_tumor
- Wikipedia: https://en.wikipedia.org/wiki/Malignant_peripheral_nerve_sheath_tumor

## Connected records

- cancers: [Desmoid tumour](https://onco.cc/cancers/desmoid-tumour/), [Epithelioid sarcoma](https://onco.cc/cancers/epithelioid-sarcoma/), [Sarcomas (soft tissue, bone, GIST)](https://onco.cc/cancers/sarcoma/), [Soft tissue sarcoma of the extremity (localised and advanced)](https://onco.cc/cancers/extremity-soft-tissue-sarcoma/), [Synovial sarcoma](https://onco.cc/cancers/synovial-sarcoma/), [Undifferentiated pleomorphic sarcoma (UPS)](https://onco.cc/cancers/undifferentiated-pleomorphic-sarcoma/)
- key papers: [EORTC 62012: doxorubicin alone versus intensified doxorubicin plus ifosfamide for first-line treatment of advanced soft tissue sarcoma](https://onco.cc/key-papers/paper-eortc-62012-doxorubicin-ifosfamide-judson-lancet-oncol-2014/), [First-line chemotherapy for malignant peripheral nerve sheath tumour versus other soft tissue sarcomas (EORTC pooled analysis)](https://onco.cc/key-papers/paper-kroep-mpnst-first-line-chemotherapy-ann-oncol-2011/), [PRC2 is recurrently inactivated through EED or SUZ12 loss in malignant peripheral nerve sheath tumours](https://onco.cc/key-papers/paper-lee-prc2-mpnst-nat-genet-2014/), [Soft tissue and visceral sarcomas: ESMO-EURACAN-GENTURIS clinical practice guideline](https://onco.cc/key-papers/paper-esmo-sts-guideline-gronchi-ann-oncol-2021/)
- drugs: [Doxorubicin](https://onco.cc/drugs/doxorubicin/), [Etoposide](https://onco.cc/drugs/etoposide/), [Ifosfamide](https://onco.cc/drugs/ifosfamide/), [Mirdametinib](https://onco.cc/drugs/mirdametinib/), [Selumetinib](https://onco.cc/drugs/selumetinib/)
- targets: [MEK1/2](https://onco.cc/targets/mek/), [TYK2](https://onco.cc/targets/tyk2/)
- pathways: [RAS / RAF / MEK / ERK (MAPK)](https://onco.cc/pathways/ras-mapk/)
- technologies: [IMRT / IGRT (modern external beam)](https://onco.cc/technologies/imrt-igrt/), [Limb-salvage surgery and endoprosthetic reconstruction](https://onco.cc/technologies/limb-salvage-surgery/), [MRI](https://onco.cc/technologies/mri/), [PET/CT](https://onco.cc/technologies/pet-ct/)
- trials: [EORTC 62012](https://onco.cc/trials/eortc-62012/)
- terms: [CDKN2A/B homozygous deletion](https://onco.cc/terms/cdkn2a-homozygous-deletion/)

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JSON: https://onco.cc/api/v1/entities/malignant-peripheral-nerve-sheath-tumour.json