It's Always Been Like That - Abstract

MRI showed a 6 cm left frontal enhancing mass causing significant mass effect and displacement of the optic chiasm (Figure 3). CSF cleft and white matter buckling signs suggested an extra-axial origin of the tumor. The patient underwent subtotal neurosurgical resection (80-90%) of the mass, which was felt intraoperatively to be an intraparenchymal tumor without adhesion to the skull base. Histopathologic analysis of the tissue revealed nests of epithelioid cells positive for MART-1 and MITF (Figure 4). Additional stains including GFAP, synaptophysin, Olig2, EMA, PR, Oct3/4, AE1.3/CAM5.2, and desmin were negative. The tumor was positive for pathogenic variants in GNAQ (including Arg183Gln), which are reported to occur in 50% of uveal melanomas Co-Authors[1]. A complete skin examination revealed no evidence of a primary cutaneous melanoma. Follow up examination 3 weeks later revealed stable afferent function, normal intraocular pressures, significant improvement in papilledema, and no evidence of focal lesions in the peripheral fundus. In the following months, the patient graduated high school. He underwent radiation and 4 cycles of ipilimumab and nivolumab that were complicated by high-grade fevers, hemolytic anemia, and that responded to corticosteroid therapy. MRI of the cervical spine 5 months after his initial presentation showed new diffuse nodular leptomeningeal enhancement consistent with metastases that was confirmed on cytology of cerebral spinal fluid. The patient was later hospitalized with headaches and confusion and repeat MRI of the brain showed evidence of hydrocephalus secondary to progressive leptomeningeal disease. A ventriculoperitoneal shunt was placed. Shortly thereafter, the patient had a tonic seizure and hypoxic respiratory failure requiring intubation. A new tumor focus was found near the intracranial portion of the shunt and the shunt was revised. Following extubation and discussion with the family, the patient was discharged home with Hospice care and passed away 1 month later.

"It's Always Been Like That" Eric Gaier1, William Butler2, Joseph Rizzo1 , Joseph F Rizzo III MD 1 Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, USA, 2Massachusetts General Hospital, Boston, Massachusetts, USA History & Exam An 18 year-old Caucasian boy presented with left upper eyelid ptosis, headaches, and iris heterochromia. The patient and his family reported the left iris being darker than the right since early childhood. Over the 5 years preceding his presentation, the patient's mother noted progressive ptosis of his left upper eyelid. A top student in middle school, his grades had declined through high school, and his family had noticed loss of motivation mixed with intermittent irritability and mood changes. The patient developed headaches 2 years prior that had been worsening steadily and culminated over the preceding week in severity with daily episodes of nausea and vomiting. He noticed increased thirst and voiding frequency and had felt fatigued. He gained 25 lbs in the preceding 3 months. The patient was initially prescribed sumatriptan and cyproheptadine for presumed migraines without symptomatic benefit. In the week prior to presentation, the left side of his face began to droop and he developed binocular, horizontal diplopia. A CT head was abnormal, and the patient was referred for evaluation and admission. External examination revealed ptosis of the left upper eyelid and slate grey circumferential coloration of the sclera (Figure 1). The right iris was hazel, and the left was dark brown. The pupils were equal and reactive without a relative afferent defect. Visual acuities were 20/20 OU without dyschromatopsia or metamorphopsia. Abduction of the left eye was mildly limited, and there was subtle left facial weakness. Automated visual field testing showed enlarged blind spots bilaterally. Funduscopic examination was significant for papilledema with peripapillary flame hemorrhages OU and a striking interocular diffuse choroidal pigmentation disparity with the left eye being darker than the right (Figure 2). The patient was treated with corticosteroids with improvement of his headache and resolution of diplopia. A diagnostic procedure was performed. Financial Disclosures: The authors had no disclosures. Grant Support: None. 2018 Annual Meeting | 37 "It's Always Been Like That" Answer Final Diagnosis Primary central nervous system melanoma, likely leptomeningeal, in association with Nevus of Ota Summary of Case MRI showed a 6 cm left frontal enhancing mass causing significant mass effect and displacement of the optic chiasm (Figure 3). CSF cleft and white matter buckling signs suggested an extra-axial origin of the tumor. The patient underwent subtotal neurosurgical resection (80-90%) of the mass, which was felt intraoperatively to be an intraparenchymal tumor without adhesion to the skull base. Histopathologic analysis of the tissue revealed nests of epithelioid cells positive for MART-1 and MITF (Figure 4). Additional stains including GFAP, synaptophysin, Olig2, EMA, PR, Oct3/4, AE1.3/CAM5.2, and desmin were negative. The tumor was positive for pathogenic variants in GNAQ (including Arg183Gln), which are reported to occur in 50% of uveal melanomas Co-Authors[1]. A complete skin examination revealed no evidence of a primary cutaneous melanoma. Follow up examination 3 weeks later revealed stable afferent function, normal intraocular pressures, significant improvement in papilledema, and no evidence of focal lesions in the peripheral fundus. In the following months, the patient graduated high school. He underwent radiation and 4 cycles of ipilimumab and nivolumab that were complicated by high-grade fevers, hemolytic anemia, and that responded to corticosteroid therapy. MRI of the cervical spine 5 months after his initial presentation showed new diffuse nodular leptomeningeal enhancement consistent with metastases that was confirmed on cytology of cerebral spinal fluid. The patient was later hospitalized with headaches and confusion and repeat MRI of the brain showed evidence of hydrocephalus secondary to progressive leptomeningeal disease. A ventriculoperitoneal shunt was placed. Shortly thereafter, the patient had a tonic seizure and hypoxic respiratory failure requiring intubation. A new tumor focus was found near the intracranial portion of the shunt and the shunt was revised. Following extubation and discussion with the family, the patient was discharged home with Hospice care and passed away 1 month later. Struggle/Dilemma of the Clinical Presentation Description Nevus of Ota is strongly associated with uveal melanoma Co-Authors[2] and rarely associated with primary central nervous system melanoma [3,4]. The differential for this patient's tumor did not initially include melanoma; the Nevus of Ota was initially felt to be unrelated to his cerebral lesion. The delay in diagnosis was driven by the undue influence of considering statistically more likely etiologies and neglecting the relevant association of Nevus of Ota with melanoma. Keywords: Papilledema, Intracranial tumors, Pediatric, headaches, Ptosis References 1. Van Raamsdonk CD, Bezrookove V, Green G, et al. Frequent somatic mutations of GNAQ in uveal melanoma and blue naevi. Nature 2009;457:599-602. 2. Shields CL, Kaliki S, Livesey M, et al. Association of ocular and oculodermal melanocytosis with the rate of uveal melanoma metastasis: analysis of 7872 consecutive eyes. JAMA Ophthalmol 2013;131:993-1003. 3. Balmaceda CM, Fetell MR, O'Brien JL, Housepian EH. Nevus of Ota and leptomeningeal melanocytic lesions. Neurology 1993;43:381-6. 4. GoldmanLevy G, Rigau V, Blechet C, et al. Primary Melanoma of the Leptomeninges with BAP1 Expression-Loss in the Setting of a Nevus of Ota: A Clinical, Morphological and Genetic Study of 2 Cases. Brain pathology (Zurich, Switzerland) 2016;26:547-50. 2018 Annual Meeting | 38