Metastatic Malignant Melanoma to the Cavernous Sinus: A Case of Recurrent Disease Presenting as Parkinson Syndrome

Clinical Correspondence Section Editors: Robert Avery, DO Karl C. Golnik, MD Metastatic Malignant Melanoma to the Cavernous Sinus: A Case of Recurrent Disease Presenting as Parkinson Syndrome Stephen C. Dryden, MD, Jeremy J. Kudrna, MS, BS, Barrett N. Thompson, MD, Rutvi B. Patel, MD, Asim F. Choudhri, MD, Lauren C. Ditta, MD Downloaded from http://journals.lww.com/jneuro-ophthalmology by BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCywCX1AWnYQp/IlQrHD3i3D0OdRyi7TvSFl4Cf3VC1y0abggQZXdgGj2MwlZLeI= on 05/04/2022 M alignant melanoma of the cavernous sinus is very rare, with only a few cases of primary, one case of metastatic disease at presentation, and no cases of recurrence with metastasis described in the literature. We describe the first reported case of recurrent metastatic melanoma of the right cavernous sinus presenting as an ipsilateral abducens palsy and Horner syndrome. A 57-year-old man with a medical history of recurrent T4aN0M0 Stage IIb melanoma of the right forehead statuspost excision with reconstruction 4 times and 30 rounds of adjunctive radiation presented to the hospital with a complaint of diplopia and right-sided radiating headache with scalp tenderness. He states that the diplopia started 1 week earlier and that the headache started 1 month earlier. He endorsed jaw claudication but denied unintended weight loss, proximal muscle weakness, fevers/chills, and night sweats. He was evaluated by ophthalmology in the emergency department and found to have a visual acuity of 20/20 in both eyes, equal and reactive pupils without an afferent pupillary defect in both eyes, and physiologic intraocular pressures. His examination was remarkable for a right-sided abducens nerve palsy with restriction of abduction in the right eye, a healed forehead incision from his previous melanoma excision, and tenderness to palpation over his right zygomatic arch. Dilated funduscopic examination was unremarkable. Computed tomography (CT) of the brain without contrast and MRI of the brain and orbits without contrast were normal. Erythrocyte sedimentation rate was 31, C-reactive protein was 10, and platelets were 256. He was started empirically on treatment dose prednisone (80 mg/day) for presumed giant cell arteritis and referred to oculoplastics for a right temporal artery biopsy. Department of Ophthalmology (SCD, BNT, RBP, LCD), Hamilton Eye Institute, University of Tennessee Health Science Center, Memphis, Tennessee; Sanford School of Medicine (JJK), University of South Dakota, Vermillion, South Dakota; Department of Radiology (AFC), Le Bonheur Children’s Hospital, Memphis, Tennessee; and Department of Ophthalmology (LCD), Le Bonheur Children’s Hospital, Memphis, Tennessee The authors report no conflicts of interest. Address correspondence to Stephen C. Dryden, MD, Department of Ophthalmology, Hamilton Eye Institute, University of Tennessee Health Science Center, 930 Madison Avenue, Suite 470, Memphis, TN 38163; E-mail: [e-mail] Dryden et al: J Neuro-Ophthalmol 2021; 41: e89-e90 A right-sided temporal artery biopsy was performed and sent to Emory Healthcare ocular pathology where it was read as negative for giant cell arteritis. The patient’s steroids were discontinued, and he was referred to neuro-ophthalmology for evaluation and management of his cranial nerve VI palsy. On presentation to neuro-ophthalmology, he complained of a 2-day history of a drooping right eyelid, right-sided neck pain, continued diplopia, and persistent right-sided headache. Ocular physical examination revealed a visual acuity of 20/20 in both eyes, a 1.5-mm reactive pupil in the right eye, and a 3-mm reactive pupil in the left eye without an afferent pupillary defect in both eyes, a right-sided abducens palsy, and a ptosis of the right upper eyelid (marginal reflex distance 0.5 mm) (Fig. 1). The patient was sent emergently to the hospital for neuroimaging to rule out cavernous sinus and carotid etiology for his new Horner syndrome. Computed tomography angiography of the head and neck were normal. MRI of the brain and stem with and without contrast showed asymmetric enlargement of the right cavernous sinus on T1-weighted imaging (Fig. 2). He was referred urgently to oncology where he underwent additional metastatic workup that revealed a metastatic lesion at the left T11 transverse process and liver. These distant metastases classify the melanoma as Stage IV. V-Raf murine sarcoma viral oncogene homolog B (B-Raf) was found to be negative. The patient was started on nivolumab and ipilimumab for which he is on his third cycle. This is the first reported case of recurrent melanoma— refractory to several excisional and radiation therapies— metastasizing to the cavernous sinus and clinically presenting with ipsilateral Horner syndrome and abducens palsy. This combination of clinical symptoms is referred to as Parkinson syndrome (1,2). Parkinson syndrome has been reported in cases of carcinomas metastatic to the cavernous sinus but is rare (3,4). None of these cases were the result of recurrent melanoma refractory to multiple treatments. Despite initially negative CT and MRI findings, our patient presented to the ophthalmology clinic with Parkinson syndrome, which warranted further investigation of the cavernous sinus. In today’s medical workplace milieu of increased documentation burden and demand for pace of services, the clinical pressure to sacrifice thoroughness is e89 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence FIG. 1. External photograph composite showing a right-sided abducens palsy on attempted right gaze. Notice the right-sided ptosis and miotic pupil indicative of a Horner syndrome in primary gaze. ever present. Standard of care remains, as in the current case, to keep the differential broad due to the abundance of vital neurovascular structures contained within the cavernous sinus and the concerning presentation of acute neurological sequelae in a patient with recurrent melanoma. Melanoma is known to metastasize through lymph nodes to the liver, lung, bone, and brain. In addition to regional and distant lymphatic spread of head and neck melanoma, spread can also occur by 2 additional mechanisms. Satellite lesions are within 2 cm of the tumor, while in-transit metastases grow 2+ cm away from the primary tumor (but not beyond regional lymph node basin). However, perineural extension of malignant melanoma along cranial nerves is a lesser known complication of malignant melanoma (5). Although our patient demonstrates radiographic evidence of distant metastases to bone and liver, we speculate that perineural invasion may also have played a role in the metastatic spread to involvement of the ipsi- lateral sympathetic nerve fibers and abducens nerve. Regardless of mechanism, astute clinical judgement uncovered new radiographic evidence of metastases, which significantly altered management from initially T4aN0M0 Stage IIb to the more dismal prognosis of T4aN2cM1c Stage IV. This case report illustrates 2 take-home points. First, treatment-resistant melanomas, particularly with localizing neurological findings, may present a diagnostic dilemma requiring a more extensive workup. Second, careful examination of patients with a confirmed history of melanoma can be prudent in catching early metastases and optimizing timing of intervention. STATEMENT OF AUTHORSHIP Category 1: a. Conception and design: S. C. Dryden, B. N. Thompson, R. B. Patel, and L. C. Ditta; b. Acquisition of data: N/A; c. Analysis and interpretation of data: N/A. Category 2: a. Drafting the manuscript: S. C. Dryden, J. J. Kudrna, B. N. Thompson, R. B. Patel, A. F. Choudhri, and L. C. Ditta; b) Revising it for intellectual content: A. F. Choudhri and L. C. Ditta. Category 3: a) Final approval of the completed manuscript: S. C. Dryden and L. C. Ditta. REFERENCES FIG. 2. Axial MRI T1 with fat saturation showing a thin section of the orbits with asymmetric enlargement of the right cavernous sinus (red arrows) compared with the left (red arrowhead). e90 1. Parkinson D, Johnston J, Chaudhuri A. Sympathetic connections to the fifth and sixth cranial nerves. Anatomical Rec. 1978;191:221–226. 2. 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