Atypical Neurofibroma
Synonyms: Neurofibroma with atypia, premalignant neurofibroma, atypical neurofibromatosis neoplasm with uncertain biologic potential (ANNUBP)
Represents a spectrum between benign neurofibroma and MPNST
Quick Facts
Behaviour
Intermediate
Category
Soft tissue
Synonyms
- Neurofibroma with atypia
- premalignant neurofibroma
- atypical neurofibromatosis neoplasm with uncertain biologic potential (ANNUBP)
Category
Soft tissue
Behaviour
Intermediate
Gender
M = F
Tissue of Origin
Neural
Epidemiology
- Rare; occurs predominantly in NF1 patients
- Risk of malignant transformation to MPNST
- May arise in plexiform neurofibromas
- Poorly defined entity in current literature
Clinical Features
- Pain or rapid growth in previously stable neurofibroma (red flag)
- Associated with NF1 stigmata (café-au-lait spots, axillary freckling)
- Neurological deficits if large nerve involvement
- Often impossible to distinguish from MPNST clinically
Location
- Deep soft tissue along major nerve trunks
- Any location typical for neurofibroma
- Paravertebral and retroperitoneal in NF1
Imaging
- Fusiform nerve sheath mass on MRI
- Loss of target sign (seen in Benign neurofibroma) may indicate atypia
- High SUV on FDG-PET suggests Malignant transformation
- MRI cannot reliably distinguish atypical from Malignant PNST
Pathology
- ANNUBP is pathologically defined by the presence of at least 2 of the following:
- nuclear atypia
- hypercellularity
- variable loss of neurofibroma architecture
- mitotic activity beyond isolated mitotic figures
Genetics
- CDKN2A deletion in 50% - marker of malignant potential
- Loss of H3K27me3 expression in 50%
- Retains S100 positivity unlike High-grade MPNST
- NF1 mutation (germline or somatic) as background
Treatment
- Wide local excision recommended
- Close surveillance given malignant potential
- No established chemotherapy role for atypical neurofibroma alone
Prognosis
- Intermediate - risk of progression to MPNST
- Estimated 10-year risk of transformation 10–30% in NF1
- Complete excision with negative margins is primary goal
Key Points
- Represents a spectrum between benign neurofibroma and MPNST
- CDKN2A loss and H3K27me3 loss are molecular markers of progression
- FDG-PET useful to identify lesions at highest risk of malignant transformation in NF1
- Diagnosis requires careful pathological assessment
Workup - Blood Tests
- FBC, U&E, LFTs - baseline
- No specific tumour markers
Workup - Local Imaging
MRI primary site
Workup - Biopsy
Core needle biopsy - multiple cores to capture most cellular/atypical region
Workup - Staging
- FDG-PET-CT - for NF1 patients to survey all plexiform neurofibromas simultaneously
- CT chest if MPNST transformation suspected
Workup - Other
- Genetics/NF1 specialist referral if not already under NF1 service
- MDT review at soft tissue sarcoma centre
Follow-up Summary
- 1
Intermediate soft tissue/nerve sheath tumour with Malignant potential - Follow-up required
- 2
Post-op visit at 6 weeks
- 3
Year 1–2
6-monthly clinical review; MRI primary site if incompletely excised or NF1 context
- 4
FDG-PET surveillance for NF1 patients with residual plexiform neurofibromas - monitor for MPNST transformation
- 5
If NF1
annual clinical review; FDG-PET if new symptoms or rapid growth of neurofibroma
- 6
Advise patient on red flags for MPNST transformation
rapid growth, new neurological deficit, pain
- 7
Genetics referral for NF1 patients if not already under specialist NF1 service
Medical disclaimer
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