Neurofibromatosis Type 1 and Type 2
Review of neurofibromatosis type 1 and type 2 for radiology board exams including the ABR Core exam. In this first of two episodes on neurofibromatosis I review key differences between NF1 and NF2.
Neurofibromatosis Type 1 and Type 2 and Neurofibromatosis Imaging Manifestations
Neurofibromatosis:
· A phakomatosis (phakomatoses=neurocutaneous disorders involving the ectoderm involving CNS and other tissues like skin). Other phakomatoses:
o Tuberous sclerosis
o Von Hippel-Lindau
o Sturge-Weber Syndrome
o NF1/NF2
o All of these are very commonly tested!
o All of these are relatively common diseases
Neurofibromatosis type 1 (NF1)
o The most common phakomatosis
§ Hence possibly the most tested
o Autosomal dominant inheritance in many but not all cases (otherwise de novo)
§ NF1 gene on chromosome 17q11.2
§ Tumor suppressor of Ras/MAPK pathway doesn’t work correctly
o Random fact: NF1 / von Recklinghausen disease and “von Recklinghausen” has 17 letters—this can help you remember this is 17q
§ Are you really going to count letters on your board exam?
o Need 2 or more of
§ At least two neurofibromas or one plexiform neurofibroma
· Plexiform neurofibroma is a benign peripheral nerve tumor
o Benign but carries risk of malignant transformation unlike cutaneous neurofibromas
o Plexiform neurofibromas involve nerves and a nerve plexus but it is overall challenging to distinguish these form other neurofibromas
o Larger lesions may be excised due to malignancy risk
o If particularly large fusiform lesion with rapid growth, consider a malignant peripheral nerve sheath tumor
§ Optic nerve glioma
§ >6 café au lait spots in one year
§ Axillary and inguinal (intertriginous) freckles
§ Osseous involvement
· Sphenoid wing dysplasia
· Pseudoarthrosis
§ 2+ iris hamartoma (Lisch nodules)
§ First degree relative with NF1
§ CAFÉ SPOT
· Café au lait spots
· Axillary/inguinal freckling
· Fibromas
· Eye hamartomas (Lisch nodules)
· Skeletal abnormalities
· Positive family history
· Optic nerve Tumors (glioma)
§ A few additional points
· NF1 presents earlier clinically than NF2
· Has MANY possible associated tumors
o Malignant peripheral nerve sheath tumors
§ 50% of these arise in patients with NF1
o Renal angiomyolipoma
o Many varieties of gliomas
o Pheochromocytoma, Wilms tumor, many more
· Neurofibroma involvement may be localized cutaneous or diffuse
o Know what neurofibromas on a mammogram look like
§ Essentially an Aunt Minnie on mammography
· Also involves vascular system
o Arteriovenous malformations, aneurysms, renal artery stenosis, coarctation of aorta
· Treatment is surgical resection of tumors with rapid enlargement
· Supportive therapy
Neurofibromatosis Type 2
§ Key point: NOT associated with neurofibromas
· Hence this was a poor choice of name…
§ Autosomal dominant inheritance
· NF2 gene on chromosome 22q12
§ CNS predominant disease with
· Schwannomas (mot common vestibular schwannomas)
· Meningiomas
· Intramedullary spinal ependymomas
§ MISME acronym
· Multiple Inherited Schwannomas Meningiomas and Ependymomas
§ If you see a meningioma in a child, consider NF2
§ Bilateral vestibular Schwannomas should be considered to represent NF2 on board examinations
· Here’s how I remember this
· NFONE—what is the ONE thing you think of with NF?
o The neurofibromas—hence this NF one has the neurofibromas
o If they show you neurofibromas on a question this is NF1
o O for Optic nerve glioma or O for orbit
· NFTWO—has two (meaning bilateral) vestibular schwannomas
o NF22: 22q is NF2
o NF2 dx in 2nd decade
· Key points to emphasize
o NF1 17q deletion and NF2 22q deletion
o NF1 has neurofibromas, NF2 sort of doesn’t
o If you see an optic nerve glioma in a kid think NF1
§ Bilateral optic nerve gliomas regardless of age think NF1
o If you see aortic coarctation in a kid/teenager, think NF1
§ Rib notching (remember 5th to 8th ribs most common with coarctation)
§ NF1 is one of few entities that can have both inferior and superior rib notching with rob notching caused by the neurofibroma and/or collaterals from aortic coarctation
o Renal artery stenosis in a teenager should make you immediately think NF1
o NF1 sphenoid dysplasia causes buphthalmos/proptosis or eye on affected side
§ Buphthalmos=enlarged eyeball due to increased intraocular pressure from sphenoid dysplasia (absent orbit)
· Think NF1 or Sturge Weber syndrome
· They can show a photo of a child/adult with a bulging, enlarged eye and you should think NF1 or Sturge Weber syndrome
o NF1 has association with elephantiasis neuromatosa
§ Focal gigantism from diffuse skin thickening/plexiform neurofibromas of an extremity
o NF1 osseous manifestations include
§ craniofacial dysplasia including sphenoid dysplasia
§ scalloped vertebrae and scoliosis, especially acute cervical kyphosis
· due to neurofibroma and dural ectasia, most common in lumbar spine
§ pseudarthroses
§ enlarged spinal neural foramen
o Schwannoma vs neurofibroma
§ Imaging appearance can overlap
§ Schwannoma is eccentric growth to nerve, can be separated form nerve with surgery
§ Neurofibromas infiltrate the nerve and resection requires nerve sacrifice
§ If a lesion is intracranial this is most likely a schwannoma, and you should think NF2
· If an orbital lesion is present think NF1
§ In the spinal canal these are both extramedullary intradural lesions
· Schwannoma, meningioma, neurofibroma, drop metastases
§ If you see an extraspinal lesion below the neck it is most likely a neurofibroma
§ Target sign on MRI favors neurofibroma rather than schwannoma
§ S100 staining is schwannoma, Antoni A/B pattern is schwannoma
o Lateral thoracic meningocele think NF1
§ Due to enlarged neural foramen with dural and bone insufficiency
§ A pulsion diverticulum due to negative intrathoracic pressure during respiration sucking out meningocele through the enlarged neural foramina
o Vascular anomalies think NF1
§ Aortic coarctation, renal artery stenosis, aneurysms, AV fistula
· NF1 has the skin and subcutaneous neurofibromas and NF2 has no specific skin findings
· NF1 may have foci of abnormal signal (FASI) in basal ganglia during first decade of life of uncertain etiology but benign—not tumors, this is not seen in NF2
Review:
Skin: NF1 café au lait and NF2 skin tags
Nerves: NF1 neurofibroma and NF2 schwannoma
Gliomas: NF1 astrocytoma and NF2 ependymoma
NF1 kids think pilocytic astrocytoma, adults high grade anaplastic astrocytoma/GBM
Coverings: NF1 meningoceles and dural ectasia and NF2 meningioma
Orbits: NF1 optic nerve glioma and NF2 optic nerve sheath meningioma
