Primary Diffuse Leptomeningeal Glioneuronal Tumor Presenting as Bilateral Vision Loss

A previously healthy 13-year-old Hispanic boy presented to our pediatric emergency department (ED) reporting a 3-day history of progressive, painless vision loss. The visual decline was described as blurring in the right eye (right eye) which progressed to seeing shadows alone, followed by progressive blurring of vision in the left eye (left eye). His medical history was unremarkable.

Clinical Correspondence Section Editors: Robert Avery, DO Karl C. Golnik, MD Caroline Froment, MD, PhD An-Guor Wang, MD Primary Diffuse Leptomeningeal Glioneuronal Tumor Presenting as Bilateral Vision Loss Casey G. Smith, MD, Asim F. Choudhri, MD, Jie Zhang, MD, Lauren C. Ditta, MD A previously healthy 13-year-old Hispanic boy presented to our pediatric emergency department (ED) reporting a 3-day history of progressive, painless vision loss. The visual decline was described as blurring in the right eye (right eye) which progressed to seeing shadows alone, followed by progressive blurring of vision in the left eye (left eye). His medical history was unremarkable. A thorough review of systems was negative, including denying headaches, recent travel, or known infectious exposures. The ocular history was significant for low myopia and spectacle wear. In addition, outside records documented a clinical visit 9 months prior for complaints of headaches and blurry vision, for which the patient had been given a diagnosis of pseudopapilledema with a recommendation for follow-up in 6 months. His best-corrected visual acuity at that time was 20/25 in the right eye and 20/20 in the left eye. Initial examination in the ED revealed near visual acuity of light perception in the right eye and 20/400 in the left eye, with a brisk afferent pupillary defect in the right eye. Anterior segment examination and intraocular pressures were unremarkable. On dilated fundus examination, there was marked bilateral optic nerve edema with obliteration of the optic cup and peripapillary hemorrhages, worse in the right eye, and a gliotic membrane overlying both discs. Macular exudates were also present in both eyes. Perivascular clusters of hemorrhage were present in the peripheral Department of Ophthalmology (CGS, LD, AC), University of Tennessee Health Science Center, Hamilton Eye Institute, Memphis, Tennessee; Le Bonheur Children’s Hospital Neuroscience Institute (LD, AC), Memphis, Tennessee; Department of Ophthalmology (LD), St. Jude Children’s Research Hospital, Memphis, Tennessee; Department of Pediatrics (LD), Le Bonheur Children’s Hospital, Memphis, Tennessee; Department of Radiology (AC), University of Tennessee Health Science Center, Memphis, Tennessee; Department of Pathology (JZ), Le Bonheur Children’s Hospital, Memphis, Tennessee; and Department of Pathology (JZ), University of Tennessee Health Science Center, Memphis Tennessee. The authors report no conflicts of interest. This case report was conducted at the University of Tennessee Health Science Center and Le Bonheur Children’s Hospital, Memphis, TN. This case study was HIPAA compliant and performed after parental consent. Address correspondence to Casey G. Smith, MD, Department of Ophthalmology, University of Tennessee Health Science Center, Hamilton Eye Institute, 930 Madison Avenue Suite 400, Memphis, TN 38103; E-mail: [e-mail] Smith et al: J Neuro-Ophthalmol 2023; 43: e3-e5 retina; however, there was no obvious vascular sheathing, vitritis, or retinal necrosis. The patient underwent MRI of the brain, orbits, spine, and MR angiography. On MRI of the brain and brainstem, the patient had bony remodeling consistent with chronic communicating hydrocephalus, diffuse enhancement both of the thecal sac and along the surface of the brainstem, and nonenhancing material in the atrium and occipital horn of the lateral ventricle with an area of nodular enhancement along the border of the ventricle. MRI orbits showed cerebrospinal fluid (CSF) distention of the bilateral optic nerve sheaths and bilateral optic nerve elevation, consistent with papilledema (Fig. 1). The patient was admitted to the general pediatrics service with a multidisciplinary approach to care. A workup was initiated to rule out an infectious, inflammatory, or neoplastic process. Testing for tuberculosis, Bartonella henselae, toxoplasmosis, neurocysticercosis, histoplasmosis, neurosyphilis, HIV, disseminated hepatitis B, and blood cultures were unremarkable. A lumbar puncture revealed an elevated opening pressure of greater than 37 cm H20 and clear CSF with a high protein of 785 and no elevated white count. CSF meningoencephalitis panel and cytology were unremarkable. The following day the patient woke up complaining of no light perception vision in the right eye. Therefore, the decision was made by neurosurgery to proceed with emergent external ventricular drainage device placement for CSF diversion. Within the week, he also underwent bilateral optic nerve sheath fenestrations with the goal to preserve vision and protect his optic nerves. After these, the patient’s vision was light perception in the right eye and 20/200 in the left eye. The patient’s serologic and CSF workup remained negative. Concerned for continued elevated intracranial pressure, neurosurgery proceeded with a ventricular biopsy and ventriculoperitoneal shunt for definitive CSF diversion. Tissue biopsy revealed a low-grade neuroepithelial neoplasm without BRAF mutation, which in conjunction with the MRI findings was consistent with a diagnosis of diffuse leptomeningeal glioneuronal tumor (DLGNT) (Fig. 1). The patient subsequently underwent craniospinal irradiation. After treatment, he had no improvement in vision. He is currently seeing the low vision service and is working with occupational therapy. e3 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence FIG. 1. MRI with and without contrast of the brain and orbits. A. Axial T2W image shows debris in the atrium of the right lateral ventricle (red arrow) and juxtacortical cysts in the right superior temporal gyrus (red arrowhead). The inner table of the calvarium is identified as a T2W hypointense rim (white arrow), and there is scalloping of the interface of the meninges and the inner table of the calvarium (white arrowheads), which is a sign of chronic elevated intracranial pressures. B. Axial FIESTA image shows bilateral optic nerve head elevation (red arrowheads) and CSF distension of the optic nerve sheaths (red arrow). There is enlargement of the temporal horns of both lateral ventricles (black arrowheads). C. Axial T1W image after gadolinium administration shows leptomeningeal enhancement along the surface of the brainstem (red arrowhead). DLGNT, also known as a disseminated oligodendrogliallike leptomeningeal tumor of childhood (1), is a rare neoplasm which has only been described as a unique clinical entity by the WHO since 2016 (2). It is characterized by the presence of communicating hydrocephalus, diffuse leptomeningeal enhancement, cystic changes on MRI, absence of tumor cells in the CSF, and a cell population of both glial and neuronal copositivity (3). It is a slow-growing tumor; hence, our patient’s findings of bony remodeling on MRI consistent with chronic hydrocephalus. Pathologic diagnosis and molecular evaluation of this tumor can be challenging because of the typically small amount of tissue that can safely be obtained at the time of biopsy (4). In addition, DLGNT has various clinical manifestations and can be easily misdiagnosed (5). Microscopically, this tumor consists of small round oligodendroglia-like cells and myxoid matrix (Fig. 2A, B). Tumor cells have mild pleomorphism and variable cellularity (Fig. 2C), and focal remote hemorrhage with hemosiderin deposits is present. No ganglion cell differentiation, mitosis, necrosis, or microvascular proliferation is revealed. These tumor cells are diffusely immunoreactive for OLG2, weakly immunoreactive for synaptophysin, and immunonegative for BRAF V600E. Ki67/Mib-1 immunostain shows a very low proliferative rate. These tumor cells do not demonstrate BRAF gene duplication, loss of chromosome 1p, or gain of chromosome 1q (EXO1) by fluorescence in situ hybridization (FISH). This case highlights the importance of close observation with a low threshold to workup patients with possible optic nerve head edema as well as the importance of multidisciplinary collaboration in diagnosing and caring for these patients. Our patient presented 9 months previously to an outside provider complaining of blurry vision and headaches and was noted to have elevated discs. Despite “good vision” at the time, there was likely true, evolving ocular pathology. A thorough workup, including serial optic nerve photos, enhanced depth imaging optical coherence tomography, fundus autofluorescence, B-scan ultrasonography, FIG. 2. Tumor cells are small round oligodendroglia-like cells with myxoid matrix (1A and 1B, H&E, ·200), mild pleomorphism, and variable cellularity (1C, H&E, ·4). e4 Smith et al: J Neuro-Ophthalmol 2023; 43: e3-e5 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence and visual field testing, is critical to ruling out true edema. In addition, close monitoring with repeat examinations is warranted, especially if there are visual symptoms, an unclear diagnosis, or if diagnostic testing is ongoing. In summary, DLGNT is a rare pediatric neoplasm with an indolent course that presents with signs of hydrocephalus, diffuse leptomeningeal enhancement, and an absence of tumor cells in the CSF. The ophthalmologist must have a high index of suspicion when noting new bilateral optic nerve head edema in a patient with a low threshold to proceed with further workup to make a diagnosis. STATEMENT OF AUTHORSHIP Conception design: C. G. Smith, L. Ditta, A. Choudhri, J. Zhang; Acquisition of data: C. G. Smith, L. Ditta, A. Choudhri, J. Zhang; Analysis and interpretation of data: C. G. Smith, L. Ditta, A. Choudhri, J. Zhang. Drafting the manuscript: C. G. Smith, L. Ditta, A. Choudhri, J. Zhang; Revising it for intellectual content: C. G. Smith, L. Ditta, A. Choudhri, J. Zhang. Final approval of the completed manuscript: C. G. Smith, L. Ditta, A. Choudhri, J. Zhang. Smith et al: J Neuro-Ophthalmol 2023; 43: e3-e5 REFERENCES 1. Lee JK, Ko HC, Choi JG, Lee YS, Son BC. A case of diffuse leptomeningeal glioneuronal tumor misdiagnosed as chronic tuberculous meningitis without brain biopsy. Case Rep Neurol Med. 2018;2018:1391943. 2. Lyle MR, Dolia JN, Fratkin J, Nichols TA, Herrington BL. Newly identified characteristics and suggestions for diagnosis and treatment of diffuse leptomeningeal glioneuronal/ neuroepithelial tumors: a case report and review of the literature. 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Accessed February 10, 2021. e5 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.