Introduction
Neurofibromatosis type 1 (NF1) is a genetic disorder known for cutaneous signs such as café-au-lait macules and axillary freckling, as well as neurofibromas and CNS involvement. While many NF1 manifestations are well described, craniofacial and CNS presentations can be uncommon and radiologically nuanced. This article synthesizes four case reports that highlight unusual MRI findings in NF1 patients, emphasizing diagnostic challenges, imaging features, and clinical management implications.
Case 1: Leptomeningeal angiomatosis in an NF1 patient with concurrent craniofacial anomalies
A 19-year-old female with multiple café-au-lait macules and a family history of NF1 presented with right upper eyelid swelling. MRI revealed a dorsal midbrain–pons glioma with typical T2/FLAIR hyperintensity and mild enhancement, alongside focal areas of signal intensity (FASI) in the insular cortex and cerebellum. A noteworthy finding was an ill-defined right supraorbital plexiform neurofibroma extending medially into the preseptal space, displaying target sign on imaging and robust post-contrast enhancement.
Additionally, a small right anterior frontoethmoidal encephalocele and a smaller subcentimetric meningocele were detected, with leptomeningeal enhancement in the parieto-temporal region. Mineralization on susceptibility sequences and calcifications on CT supported a complex picture with vascular-caliber considerations. The most striking and novel observation was leptomeningeal angiomatosis, evidenced by prominent leptomeningeal enhancement and a dominant cortical vein draining into the superior sagittal sinus. The combination of NF1 with leptomeningeal angiomatosis is exceedingly rare and, to our knowledge, not previously reported in the NF1 literature. The management plan favored surgical repair of the encephalocele while adopting conservative surveillance for other intracranial findings.
Case 2: NF1-associated gliomas and corpus callosum involvement
An 11-year-old with established NF1 presented for postoperative follow-up after a posterior fossa pilocytic astrocytoma (Grade 1). Contrast-enhanced MRI identified residual solid-cystic lesions spanning the bilateral superior cerebellar peduncles, cerebellar vermis, midbrain tectal plate, and right cerebellar hemisphere with fourth-ventricle extension. The solid component showed isointense T1 signals and heterogeneous T2/FLAIR hyperintensity with irregular enhancement, while the cystic part was T1-hypointense and T2-hyperintense with peripheral post-contrast enhancement only.
A second smaller lesion arising from the corpus callosum mid-body appeared as hypointense on T1, hyperintense on T2, and heterogeneously hyperintense on FLAIR, with disk-like post-contrast enhancement. Together, these imaging findings favored lineages of glioma in a patient with NF1, underscoring the spectrum of CNS involvement in this population and the need for ongoing tumor surveillance in NF1-related gliomatosis.
Case 3: Large craniofacial plexiform neurofibroma with traumatic hematoma and skull dysplasia
A 28-year-old man with NF1 presented with long-standing left craniofacial swelling, aggravated after minor trauma. Initial non-contrast CT showed a large hyperdense hematoma within a bulky soft-tissue mass and notable bony dysplasia (sphenoid, zygoma, zygomatic arch, and calvarium thinning). Contrast-enhanced MRI six weeks later demonstrated a partially resolved subacute hematoma within a large left craniofacial plexiform neurofibroma extending over multiple compartments. The plexiform component appeared isointense to hypointense on T1-WI, variably hyperintense on T2-WI, and demonstrated heterogeneous enhancement with internal target-like patterns in places.
The lesion also involved peripherally the facial artery on TOF MRA, consistent with the vascularity often seen in plexiform neurofibromas. At follow-up, the hematoma largely resolved, while the primary plexiform neurofibroma remained, illustrating the potential for traumatic events to complicate NF1 with hemorrhagic episodes within vascularized plexiform lesions and the value of serial imaging to guide management.
Case 4: Diffuse and plexiform neurofibromas in the lower face with incidental FASI
A 5-year-old boy with NF1 and family history presented with congenital left-sided facial swelling. Ultrasonography identified a left buccal plexiform neurofibroma without internal vascularity. MRI revealed concurrent diffuse neurofibroma in the left lower face and a left buccal/submandibular plexiform lesion encasing the facial artery with heterogeneous enhancement. The brain MRI showed FASI in bilateral globus pallidus, the right cerebral peduncle, bilateral dentate nuclei, and subcortical white matter of the temporal lobes—consistent with common NF1-associated FASI patterns in pediatric patients.
Given the stable clinical trajectory and lack of significant progression, the team pursued conservative management with ongoing clinical and imaging follow-up rather than immediate surgical intervention.
Discussion: Why these cases matter for NF1 care and radiology practice
NF1 mutations disrupt neurofibromin and dysregulate RAS signaling, rendering patients susceptible to multiple tumor types and CNS anomalies. While classic NF1 signs are well known, these cases emphasize several critical radiology and clinical considerations:
- Uncommon CNS lesions, including gliomas in non-optic pathways and corpus callosum involvement, require careful MRI characterization to differentiate from benign mimics such as FASI and demyelination.
- Plexiform neurofibromas are hallmark NF1 lesions with extensive craniofacial involvement and a non-negligible risk of malignant transformation; imaging helps monitor growth, vascularity, and potential preoperative planning.
- Leptomeningeal angiomatosis, though rare in NF1, represents a crucial diagnostic possibility that can mimic other leptomeningeal diseases. Recognition hinges on contrast enhancement patterns and venous drainage features.
- Encephaloceles and meningoceles, though uncommon, may arise from skull dysplasia in NF1 and require multidisciplinary management, including neurosurgery and craniofacial teams.
- FASI are frequent in pediatric NF1 and can resemble neoplasia on MRI. Recognizing their typical distribution and behavior over time helps avoid unnecessary interventions.
These cases collectively illustrate the breadth of craniofacial and CNS manifestations in NF1 and underscore the essential role of MRI in guiding diagnosis, prognosis, and management. Regular imaging follow-up and a multidisciplinary approach remain central to optimizing outcomes for NF1 patients with complex craniofacial and CNS involvement.
