Perineural Spread of Squamous Cell Carcinoma Without Enlargement or Enhancement of Involved Nerves

A 68-year-old patient initially presented 4 years earlier to a local neurologist for left-sided oral numbness that was attributed to partial traumatic CN VII palsy (noted after a minor fall without loss of consciousness or facial bruising).

Surgeons' Corner Section Editors: Vivek R. Patel, MD Prem Subramanian, MD, PhD Perineural Spread of Squamous Cell Carcinoma Without Enlargement or Enhancement of Involved Nerves Eric R. Williams, MD, Prem S. Subramanian, MD, PhD A 68-year-old patient initially presented 4 years earlier to a local neurologist for left-sided oral numbness that was attributed to partial traumatic CN VII palsy (noted after a minor fall without loss of consciousness or facial bruising). No other neurological deficits were noted at the time. She returned 2 years later with blurred vision of the left eye and worsening facial asymmetry and had left CN V1, V2, VI, and VII dysfunction. MRI of brain and orbits demonstrated an enhancing lesion of the left mandibular branch of the trigeminal nerve, and further workup including lumbar puncture was unrevealing. She was prescribed valacyclovir and prednisone for presumed postherpetic disease, after which repeat MRI demonstrated decreased enhancement. Over the next year, penetrating keratoplasty (PKP) for corneal scarring and resultant decreased visual acuity and eyelid/facial surgeries for lagophthalmos and cheek deformity were performed. When symptoms persisted and progressed, she was referred to our neuro-ophthalmology service. On presentation to us, left CN V1, V2, VI, and VII deficits were evident during examination (Fig. 1). A key part of her history, not noted in previous records, was Mohs surgical excision 10 years earlier of a squamous cell carcinoma just lateral to the left FIG. 1. External photograph of patient on follow-up after surgery (unchanged from presentation to neuro-ophthalmology clinic). Note left CN VII upper and lower weakness, lagophthalmos, and evidence of LUL gold weight. Included with permission from the patient. Departments of Ophthalmology, Neurology, and Neurosurgery, University of Colorado School of Medicine, Aurora, Colorado. P. S. Subramanian is a consultant for Horizon Therapeutics and GenSight Biologics. He has received research funding from GenSight Biologics, Santhera Pharmaceuticals, and Quark Pharmaceuticals. He is on the editorial board of the Journal of Neuro-Ophthalmology. The remaining author reports no conflicts of interest. Address correspondence to Prem S. Subramanian, MD, PhD, Sue Anschutz-Rodgers UC Health Eye Center, 1675 Aurora Ct Mailstop F731, Aurora, CO 80045; E-mail: Prem.subramanian@cuanschutz. edu Williams and Subramanian: J Neuro-Ophthalmol 2020; 40: e3-e4 FIG. 2. T1 precontrast coronal MRI orbits demonstrating a normal-sized (arrow) left infraorbital nerve that did not enhance with gadolinium contrast (image not shown as it was degraded by motion artifact). e3 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Surgeons' Corner oral commissure. We obtained repeat MRI orbits (Fig. 2) that showed a normal-sized infraorbital nerve on the left (not well visualized on the right). We suspected perineural spread of cancer as the cause of her symptoms and findings, and despite a lack of nerve enlargement or enhancement on orbital MRI, we advised biopsy of the infraorbital nerve because of its accessibility and low morbidity of an anterior orbitotomy. Histology demonstrated peripheral nerve infiltrated by tumor, which was consistent with squamous cell carcinoma. Radiation treatment and chemotherapy were initiated. This case demonstrates multiple key points of perineural invasion of local tumors. The presence of multiple, unilateral cranial nerve palsies raised the specter of a local, rather than a systemic, process. Because the involved cranial nerves arise disparately in the brainstem and do not e4 converge anatomically until they pass through the skull base, a high index of suspicion must exist for a process in this area. Imaging findings may be subtle. Squamous cell carcinoma characteristically spreads along nerves, and this patient's history of this condition was unfortunately overlooked for years. Because of her delayed diagnosis, she underwent multiple procedures to improve her symptoms (gold weight placement, PKP, rhytidectomy, facial sling, and tarsorrhaphy); these procedures failed as her untreated disease progressed. Finally, biopsy allowed definitive diagnosis and was undertaken based on anatomic suspicion, not imaging findings. Absence of imaging abnormalities should not dissuade the surgeon from attempting to find an answer; biopsies of affected nerves rarely add morbidity given the delayed diagnosis and significant involvement before surgery. Williams and Subramanian: J Neuro-Ophthalmol 2020; 40: e3-e4 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.