Introduction
Neurofibromatosis type 1 (NF1) is a hereditary disorder driven by mutations in the NF1 gene on chromosome 17q11.2, encoding the tumor suppressor neurofibromin. While café-au-lait macules and cutaneous neurofibromas are hallmarks, NF1 can manifest in the craniofacial region and central nervous system in uncommon and clinically significant ways. This article syntheses four distinctive cases, emphasizing magnetic resonance imaging (MRI) findings that broaden the radiologic spectrum of NF1 and illustrate how imaging guides management.
Case 1: Leptomeningeal Angiomatosis with Encephalocele in NF1
A 19-year-old female presented with right upper eyelid swelling and widespread café-au-lait spots, with a family history of NF1. MRI of brain and orbit disclosed a small brain stem glioma at the dorsal left midbrain–pontine junction and multiple focal areas of signal intensity (FASI) in the anterior right insular cortex and cerebellar hemispheres. A notable finding was an ill-defined right supraorbital plexiform neurofibroma extending into the preseptal space with target sign post-contrast enhancement.
Crucially, imaging revealed a right frontoethmoidal encephalocele through the cribriform plate into the anterior ethmoid air cells and a smaller subcentimetric meningocele in the orbit. Post-contrast MRI showed leptomeningeal enhancement along the right parieto-temporal region and interhemispheric fissure with mineralization on susceptibility imaging and mild cortical atrophy. CT confirmed calcifications. The imaging constellation favored leptomeningeal angiomatosis, a hallmark of Sturge–Weber syndrome, here observed in an NF1 patient—a rare association not previously documented in the NF1 literature according to current reviews. The patient underwent surgical planning for encephalocele repair, with conservative management for other intracranial findings.
This case underscores the importance of comprehensive imaging in NF1, where vascular malformations can co-exist or obscure tumor-related pathology. Leptomeningeal angiomatosis can mimic infectious or malignant processes; hence, recognizing its imaging signature—prominent cortical veins, leptomeningeal enhancement, and calcifications—is critical for appropriate management.
Case 2: Posterior Fossa Glioma Post-Pilocytic Astrocytoma Resection
An 11-year-old with known NF1 and prior posterior fossa pilocytic astrocytoma status presented for MRI follow-up. Contrast-enhanced MRI showed residual solid-cystic lesion involving the bilateral superior cerebellar peduncles, cerebellar vermis, midbrain including the tectal plate, and right cerebellar hemisphere with fourth ventricle extension. The solid component was isointense on T1 and heterogeneously hyperintense on T2/FLAIR, with heterogeneous post-contrast enhancement. The cystic portion was hypointense on T1, hyperintense on T2, and did not show FLAIR suppression, exhibiting peripheral enhancement.
A second smaller lesion arose from the mid-body of the corpus callosum, displaying hypointense T1, hyperintense T2, and FLAIR hyperintensity with disk-like solid enhancement post-contrast. The imaging pattern suggested glioma with NF1-associated changes. The corpus callosum involvement is relatively rare in NF1-related gliomas and demands careful longitudinal imaging to differentiate progression from treatment-related changes or benign fluctuations in FASI.
Case 3: Large Craniofacial Plexiform Neurofibroma with Hematoma Resolution
A 28-year-old man with NF1 reported a long-standing left craniofacial swelling that enlarges after trivial trauma. Initial non-contrast CT showed a large hyperdense hematoma within a hyperdense soft tissue mass, alongside craniofacial bone dysplasia (left sphenoid wing, zygoma dysplasia, thinning of the left frontal/parietal bones, and upper alveolar arch involvement).
Subsequent contrast-enhanced MRI demonstrated partially resolved subacute hematoma within a large left craniofacial plexiform neurofibroma, with the lesion extending across the left fronto-parieto-temporo-occipital region. The plexiform component appeared heterogeneous on T1 and T2, with post-contrast enhancement and internal target-like patterns. The facial artery and branches traversed the lesion on MR angiography, highlighting high vascularity. Despite a sizable hematoma and vascular involvement, follow-up imaging showed marked hematoma resolution with persistent plexiform disease. This case illustrates the dynamic interplay between hemorrhage and tumor biology in NF1 and reinforces the potential for spontaneous hematoma resolution without intervention, a fortunate trajectory in select patients.
Case 4: Concurrent Diffuse and Plexiform Neurofibromas in the Lower Face
A 5-year-old boy with NF1 and a family history of the disease presented with congenital left-sided facial swelling and pain, accompanied by numerous café-au-lait macules. Ultrasonography identified a plexiform neurofibroma in the left buccal space without internal vascularity, differentiating it from a vascular malformation. MRI confirmed diffuse neurofibroma in the left lower cheek and a left buccal/submandibular plexiform component encasing the facial artery, with iso- to hypointense T1 signals and hyperintense T2 signals with heterogeneous post-contrast enhancement. Diffuse disease involved skin and subcutaneous tissues with similar signal characteristics, reflecting extensive infiltration.
Brain imaging revealed FASI across several regions, including bilateral globus pallidus, right cerebral peduncle, dentate nuclei, and subcortical white matter of the temporal lobes. Given the stability of the clinical course, management remained conservative with ongoing clinical and imaging surveillance. The coexistence of diffuse and plexiform neurofibromas in the same patient is rare and highlights the spectrum of peripherally based NF1 lesions that can bear clinical significance for disfigurement and surgical planning.
Imaging, Pathophysiology, and Clinical Implications
NF1 is autosomal dominant with variable expressivity. Neurofibromin loss leads to dysregulated RAS signaling and tumorigenesis, producing diverse craniofacial and CNS manifestations. The four cases emphasize several key radiologic themes:
- Heterogeneous CNS involvement in NF1 includes gliomas in unusual locations such as the brainstem and corpus callosum, requiring thoughtfulness in differential diagnosis and follow-up scheduling.
- Plexiform and diffuse neurofibromas in the facial region can be extensive and highly vascular, complicating surgical planning and elevating the risk of hemorrhage and disfigurement.
- Leptomeningeal angiomatosis, although typical for Sturge–Weber syndrome, may rarely occur with NF1 and should be considered when leptomeningeal enhancement, cortical calcifications, and prominent deep venous drainage are present.
- FASI remains a common incidental finding in pediatric NF1 patients. Recognizing FASI versus neoplastic progression is essential to avoid unnecessary interventions; longitudinal imaging and stability are reassuring.
The cases also underscore the value of multimodal imaging—MRI with contrast, diffusion sequences, susceptibility-weighted imaging (SWI), and MR angiography—as well as cross-sectional CT when calcifications or complex bony anatomy are involved. This comprehensive approach informs prognosis, guides surgical planning (e.g., encephalocele repair, resection strategies for plexiform lesions), and supports careful monitoring for malignant transformation in high-risk NF1 lesions.
Conclusion
The presented case series expands the spectrum of uncommon craniofacial and CNS manifestations in NF1 detected by MRI. Clinicians and radiologists should maintain a high index of suspicion for rare associations, such as leptomeningeal angiomatosis and encephaloceles, while recognizing typical NF1 features like FASI and plexiform neurofibromas. Through vigilant imaging and multidisciplinary care, NF1 patients can receive timely interventions and appropriate surveillance tailored to their unique craniofacial and CNS involvement.
