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.
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 | NF1, chromosome 17; neurofibromin (RAS GAP) | NF2, chromosome 22; merlin |
| Frequency | Common (about 1 in 3000) | Rare |
| Nerve tumours | 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.
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.
Elsewhere in DurgiPedia
Connections
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 (MedlinePlus, US National Library of Medicine, 2025); Soft Tissue Sarcoma Treatment (PDQ®)–Health Professional Version (National Cancer Institute, 2025).
Spotted a mistake?We are always improving for the community. Tell us what is wrong and our team will review it.Report a mistake
Representative model, for educational purposes only.