[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [General pathology](https://durgical.com/en/general-pathology/) › [Peripheral nerve and skeletal muscle](https://durgical.com/en/general-pathology/areas/nerve-muscle/) › Neurofibroma, NF1 and MPNST

# Neurofibroma, NF1 and MPNST

- Lesion

Neurofibromas are soft nerve-sheath tumours, many of them in NF1. The large plexiform ones can turn into a deadly sarcoma.

Updated Nov 12, 2026

## Key points

- NF1 gene on chromosome 17; neurofibromin inactivates RAS; about half of cases are new mutations.
- NF1 features: café-au-lait spots, axillary and inguinal freckling, cutaneous and plexiform neurofibromas, Lisch nodules (iris hamartomas), optic glioma, bone lesions (sphenoid dysplasia, tibial pseudarthrosis), learning problems.
- NF1 tumours: MPNST, pilocytic astrocytoma, GIST, pheochromocytoma, juvenile myelomonocytic leukaemia, breast cancer.
- Plexiform neurofibroma: 'bag of worms' thickening of nerve plexuses; risk of MPNST; MEK inhibitors can shrink them.
- MPNST: hypercellular fascicles, necrosis, many mitoses; loss of H3K27me3 (PRC2 loss, SUZ12 or EED); CDKN2A loss.
- Triton tumour: MPNST with rhabdomyoblastic differentiation.

On this page

- The basics Key points
- What it is
- Structure
- Step by step
- NF1 vs NF2
- Markers
- Memory aid
- Elsewhere in DurgiPedia

- Clinical Clinical notes

- Study Test yourself

- Connections Connections

## What it is

Neurofibromas are benign tumours of Schwann cells mixed with fibroblasts, perineurial-like cells and mast cells that grow through and around the nerve. Localized cutaneous neurofibromas are common and may be sporadic; diffuse and especially plexiform neurofibromas, which involve multiple fascicles of a large nerve, are nearly specific for neurofibromatosis type 1. NF1 is an autosomal dominant disorder of the NF1 gene, whose product neurofibromin is a GTPase-activating protein that turns off RAS. Malignant peripheral nerve sheath tumour is a high-grade sarcoma that arises in a plexiform neurofibroma or de novo, or after radiation; half occur in NF1.

## Structure

- Neurofibroma: loosely arranged spindle cells with wavy, buckled nuclei in a myxoid to collagenous stroma with 'shredded carrot' collagen and mast cells; axons run through the tumour.
- Plexiform: multiple enlarged nerve fascicles packed with neurofibroma tissue.
- MPNST: dense fascicles of atypical spindle cells alternating with less cellular areas (marbled pattern), perivascular accentuation, necrosis.
- S100 and SOX10 patchy in neurofibroma; reduced or lost in MPNST.

## Step by step

- A person with NF1 inherits one inactive NF1 allele in every cell.
- Loss of the second allele in a Schwann cell lineage releases RAS signaling.
- RAS-active Schwann cells recruit fibroblasts and mast cells and form a neurofibroma.
- In a plexiform tumour, additional losses (CDKN2A, then PRC2 genes) cause atypical neurofibroma, then MPNST.
- MPNST grows fast and spreads to the lungs.

## NF1 vs NF2

| Feature | NF1 | NF2 |
| --- | --- | --- |
| [Gene and chromosome](https://durgical.com/en/conditions/neurofibromatosis/) | NF1, chromosome 17; neurofibromin (RAS GAP) | NF2, chromosome 22; merlin |
| Frequency | Common (about 1 in 3000) | Rare |
| [Nerve tumours](https://durgical.com/en/conditions/vestibular-schwannoma/) | Neurofibromas (plexiform), MPNST | Bilateral vestibular schwannomas |
| Other tumours | Optic glioma, GIST, pheochromocytoma | Meningiomas, ependymomas |
| Skin and eye | Café-au-lait, freckling, Lisch nodules | Few café-au-lait spots, juvenile cataracts |

## Markers

- S100 and SOX10
- Loss of H3K27me3 (MPNST)
- CD34 fibroblasts in neurofibroma

## Clinical notes

- New pain, rapid growth or neurological deficit in a plexiform neurofibroma suggests MPNST and needs imaging and biopsy.
- Children with NF1 are followed for optic glioma (vision checks), scoliosis, blood pressure and learning difficulties.
- Café-au-lait spots alone are common; six or more of a set size meet one NF1 criterion.

## Memory aid

NF1 has seventeen letters and spots; NF2 has twenty-two and ears.

## Test yourself

Think of the answer, then tap the question to see it.

## What does neurofibromin do?

It is a GTPase-activating protein that switches RAS off.

## Which neurofibroma type is nearly specific for NF1 and can become malignant?

Plexiform neurofibroma.

## What are Lisch nodules?

Pigmented hamartomas of the iris in NF1.

## Which immunohistochemical loss supports MPNST?

Loss of H3K27me3, from inactivation of the PRC2 complex.

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## Elsewhere in DurgiPedia

- [Neural crest cells and their derivatives](https://durgical.com/en/embryology/neural-crest-cells-and-their-derivatives/)

## Connections

## Related 7

- [Tumour suppressor genes: RB, TP53, APC, BRCA and the two-hit hypothesis](https://durgical.com/en/general-pathology/tumour-suppressor-genes-rb-tp53-apc-brca-and-the-two-hit-hypothesis/)
- [Hereditary cancer syndromes: the table to know](https://durgical.com/en/general-pathology/hereditary-cancer-syndromes-the-table-to-know/)
- [Schwannoma and neurofibromatosis type 2](https://durgical.com/en/general-pathology/schwannoma-and-neurofibromatosis-type-2/)
- [Familial tumour syndromes of the nervous system](https://durgical.com/en/general-pathology/familial-tumour-syndromes-of-the-nervous-system/)
- [Gastrointestinal stromal tumour (GIST)](https://durgical.com/en/general-pathology/gastrointestinal-stromal-tumour/)
- [Pheochromocytoma and paraganglioma](https://durgical.com/en/general-pathology/pheochromocytoma-and-paraganglioma/)
- [Soft tissue tumours: principles](https://durgical.com/en/general-pathology/soft-tissue-tumours-principles/)

## Related conditions 3

- [Neurofibromatosis (types 1 and 2)](https://durgical.com/en/conditions/neurofibromatosis/)
- [Gastrointestinal stromal tumour (GIST)](https://durgical.com/en/conditions/gastrointestinal-stromal-tumour/)
- [Phaeochromocytoma](https://durgical.com/en/conditions/phaeochromocytoma/)

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Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.

Sources: [Neurofibromatosis type 1: MedlinePlus Genetics](https://medlineplus.gov/genetics/condition/neurofibromatosis-type-1/) (MedlinePlus, US National Library of Medicine, 2025); [Soft Tissue Sarcoma Treatment (PDQ®)–Health Professional Version](https://www.cancer.gov/types/soft-tissue-sarcoma/hp/adult-soft-tissue-treatment-pdq) (National Cancer Institute, 2025).

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Representative model, for educational purposes only.

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Source: https://durgical.com/en/general-pathology/neurofibroma-nf1-and-mpnst/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/general-pathology/neurofibroma-nf1-and-mpnst/