Orbital-periorbital plexiform neurofibroma in neurofibromatosis type 1: A rare neurocutaneous presentation with multisystem implications

Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disorder characterized by multiple neurofibromas, café-au-lait macules, axillary freckling, and distinctive osseous abnormalities. As a phakomatosis, NF1 carries significant neurological implications, including a predisposition to central nervous system (CNS) tumors such as optic pathway gliomas and malignant peripheral nerve sheath tumors (MPNSTs). Among its diverse manifestations, orbital-periorbital plexiform neurofibroma (OPPN) is relatively rare but clinically significant due to the risk of vision loss, cosmetic deformity, and malignant transformation. Here, we describe a 36-year-old female who presented with a gradually enlarging, painless swelling of the left upper eyelid over six months. Clinical examination revealed classic stigmata of NF1, including multiple cutaneous nodules and café-au-lait spots. Magnetic resonance imaging (MRI) of the brain and orbits demonstrated a diffuse soft-tissue lesion involving the left periorbital region and masticator space, with numerous cutaneous and subcutaneous neurofibromas across the scalp and face. Computed tomography (CT) identified adjacent zygomatic bone hypoplasia and sphenoid dysplasia – both characteristic features of cranio-orbital involvement. Histopathology confirmed the diagnosis of plexiform neurofibroma. Due to the lesion’s extensive infiltration and proximity to critical neuro-ophthalmic structures, a conservative, non-surgical approach was adopted. This case highlights the neurological relevance of NF1, where vigilant imaging, early recognition of CNS tumor risk, and multidisciplinary care are essential. The neurologist plays a central role in surveillance, long-term management, and incorporating emerging therapies – such as MEK inhibitors – into clinical care, ensuring improved functional outcomes and quality of life.