Table 9.

Guideline Recommendations for malignant peripheral nerve sheath tumour and atypical neurofibromatous neoplasm of uncertain biologic potential.

Malignant peripheral nerve sheath tumour and atypical neurofibromatous neoplasm of uncertain biologic potential
No	Recommendations	Strength
1	The following groups of people with NF1 should be considered at high risk of MPNST: •NF1 microdeletion affecting SUZ12 •missense variants affecting codons 844-848 •previous atypical neurofibromatous neoplasm with uncertain biologic potential (ANNUBP) •high internal tumour load on WB-MRI or large or multiple plexiform neurofibroma in absence of WB-MRI •neurofibromatous neuropathy •previous radiotherapy •a relative with NF1 and MPNST	strong
2	Clinical assessment for MPNST should consist of assessing the following: •Tumour growth: a rapid increase in the size or a change in growth rate or of an existing plexiform neurofibroma. •Pain: new and persistent, nocturnal, substantial pain/pain that is difficult to control. •New motor deficit, sensory deficit associated with any neurofibroma or peripheral nerve. This includes bladder function, bowel disturbance, swallowing problems and breathing difficulty. •Tumour consistency: development of hard nodule in a previously soft plexiform neurofibroma. People with NF1 and any of the above should be investigated for MPNST.	strong
3	When clinical signs and symptoms point towards malignancy (suspicious tumours), investigation should begin with regional MRI. Prior to surgery, MRI should be carried out and 18FDG PET MRI (preferred) or 18FDG PET CT (if 18FDG PET MRI is not available) undertaken, using visual assessment and semiquantitative assessments with a cut-off standardized uptake value.	moderate
4	In case of a suspected ANNUBP or MPNST, primary resection is recommended if it is safe and feasible. Otherwise, radiologically (preferably18FDG PET MRI) guided diagnostic biopsy should be performed. This biopsy should be taken at the discretion of a (sarcoma) multidisciplinary team, as tumours can be heterogeneous, with the potential for a false negative result by missing malignant parts of the tumour.	strong
5	There is no place for watchful waiting in MPNST and urgent surgical resection should be the mainstay for treatment (if possible), with post-operative assessment for recurrence.	strong
6	Treatment decisions, on initial surgery and/or (neo)adjuvant chemo- or radiotherapy should be guided by an experienced multidisciplinary team.	moderate
7	If a diagnosis of ANNUBP is proven by biopsy then surgery should be the primary treatment option, if this is possible with acceptable morbidity.	strong
8	If an ANNUBP cannot be resected with acceptable morbidity, initial screening with MRI should be conducted at least every 6 months. In case of tumour growth or increase in symptoms, screening should include 18FDG PET MRI (preferred) or 18FDG PET CT (if 18FDG PET MRI is not available). After an initial clinical assessment, the follow-up interval should be determined by the characteristics of the tumour.	moderate

Note. NF1 = Neurofibromatosis type 1; MPNST = malignant peripheral nerve sheath tumour; ANNUBP = Atypical neurofibromateous neoplasm of uncertain biologic potential; WB-MRI = whole-body magnetic resonance imaging; ¹⁸FDG PET MRI = 18F-fluorodeoxyglucose positron emission tomography magnetic resonance imaging; ¹⁸FDG PET CT = 18F-fluorodeoxyglucose positron emission tomography computed tomography; MRI = magnetic resonance imaging.