Bilateral Combined Hamartoma of the Retina and Retinal Pigment Epithelium in Neurofibromatosis Type 2

A 15-year-old male patient with a known history of neurofibromatosis Type 2 (NF-2) presented to a tertiary care center with progressive and bilateral vision loss. Clinical ophthalmological examination confirmed reduced visual acuity, revealing 20/50 vision on the right eye and only hand movement perception on the left eye.

Photo and Video Essay Section Editors: Melissa W. Ko, Dean M. Cestari, Peter Quiros, Kimberly M. Winges, MD MD MD MD Bilateral Combined Hamartoma of the Retina and Retinal Pigment Epithelium in Neurofibromatosis Type 2 Flávia Sprenger, MD, Kenzo Hokazono, MD, PhD, Ana Chrystina de Souza Crippa, MD, PhD, Bernardo Corrêa de Almeida Teixeira, MD A 15-year-old male patient with a known history of neurofibromatosis Type 2 (NF-2) presented to a tertiary care center with progressive and bilateral vision loss. Clinical ophthalmological examination confirmed reduced visual acuity, revealing 20/50 vision on the right eye and only hand movement perception on the left eye. Fundoscopy revealed bilateral macular hamartomatous lesions, and the optic coherence tomography demonstrated distortion and folding of the right macula, compatible with bilateral combined hamartoma of the retina and retinal pigment epithelium (CHRRPE) (Figs. 1 and 2). Investigation proceeded with MRI of the brain and spine (Fig. 3). Brain imaging showed an isointense nodular lesion, with homogeneous contrast enhancement on the right parietal lobe, suggestive of glioma. Bilateral enhancing lesions were also seen inside the internal acoustic canals, compatible with intracanalicular vestibular schwannomas. Cervical spine imaging demonstrated 2 expansive intramedullary enhancing lesions, related to ependymomas. Neurofibromatosis Type 2 is a rare genetic autosomal dominant disorder caused by mutations on the NF2 gene, responsible for Schwann cells growth. It is characterized by the development of multiple central nervous system tumors, in contrast to neurofibromatosis Type 1 and its emblematic neurocutaneous manifestations (1–3). Classical features of NF-2 include bilateral vestibular schwannomas, meningiomas, gliomas, and spinal ependymomas. Because of this, MRI screening is highly recommended (3). Clinical manifestation varies along with patient’s age, and younger patients often seek attention for ocular presentation (2). CHRRPE is a rare congenital and benign condition. It presents as a pigmented elevated tumor on the sensory retina, containing abnormal tortuous retinal vessels, some producing foci of gliosis and lipid exudates, producing tortuosity of the Departments of Radiology (FS, BCAT), Ophtalmology (KH), and Neurology (ACSC), Hospital de Clínicas, Universidade Federal do Paraná, Curitiba, Paraná, Brazil. The authors report no conflicts of interest. Address correspondence to Flávia Sprenger, MD, Rua General Carneiro, 181, Curitiba, Paraná, Brazil. Postal code 80060-900; E-mail: fl[e-mail] Sprenger et al: J Neuro-Ophthalmol 2022; 42: e591-e592 FIG. 1. Fundus photograph of the right eye (left image) and left eye (right image), demonstrating combined hamartoma of the retina and retinal pigment epithelium with complete retinal and partial retinal pigment epithelial involvement in the macula in both eyes. remaining retinal vasculature. It is commonly associated with an epiretinal membrane formation (4). FIG. 2. Optical coherence tomography and radial B-scan line of lesion anatomy. The upper image demonstrates an epiretinal membrane (arrows) causing an inner retinal traction involving the fovea on the right eye. Middle images show thickening of the neural retina with prominent glial tissue (double headed arrow) on the right eye. Inferior image demonstrates RPE involvement on the left eye. RPE, retinal pigment epithelium. e591 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Photo and Video Essay melanoma or nevus, adenoma, and adenocarcinoma (3,4). Although CHRRPE is not a diagnostic criteria for NF-2, ophthalmologists must be alert because younger patients commonly seek ocular attention before vestibular manifestations, and NF-2 must always be reminded of on ophthalmological practice, considering its early diagnosis can lead to appropriate surgical attention and central nervous system neoplasm screening, for its appropriate tertiary caring (2). FIG. 3. MRI of the brain and spine. Left upper image represents an axial postcontrast T1 of the brain, revealing an enhancing nodular lesion on the right parietal lobe, suggestive of glioma. Left inferior image (axial postcontrast T1) demonstrates bilateral enhancing lesions on the internal acoustic canals, compatible with intracanalicular vestibular schwannomas. Sagittal postcontrast T1 of the cervical spine on the right indicates 2 expansive intra-axial enhancing lesions on the bulbus and at the C3-C4 level, related to ependymomas. It occurs sporadically on general population, unilaterally, although there is a known association with both neurofibromatosis Types 1 and 2, and on these cases, occurrence is more frequently bilateral (5). The aforementioned one of the most common retinal manifestation of NF-2, after epiretinal membranes, and its presence is a poor prognosis predictor because these patients often present with more aggressive central nervous system tumors (3–6). Differential diagnosis includes retinal astrocytoma, retinoblastoma, simple retinal hamartoma, choroidal e592 STATEMENT OF AUTHORSHIP Category 1: a. Conception and design: K. Hokazono, A. C. de Souza Crippa, and B. C. de Almeida Teixeira; b. Acquisition of data: F. Sprenger, K. Hokazono, A. C. de Souza Crippa, and B. C. de Almeida Teixeira; c. Analysis and interpretation of data: F. Sprenger, K. Hokazono, A. C. de Souza Crippa, and B. C. de Almeida Teixeira. Category 2: a. Drafting the manuscript: F. Sprenger, K. Hokazono, A. C. de Souza Crippa, and B. C. de Almeida Teixeira; b. Revising it for intellectual content: F. Sprenger, K. Hokazono, A. C. de Souza Crippa, and B. C. de Almeida Teixeira. Category 3: a. Final approval of the completed manuscript: F. Sprenger, K. Hokazono, A. C. de Souza Crippa, and B. C. de Almeida Teixeira. REFERENCES 1. Grant EA, Trzupek KM, Reiss J, Crow K, Messiaen L, Weleber RG. Combined retinal hamartomas leading to the diagnosis of neurofibromatosis type 2. Ophthalmic Genet. 2008;29:133– 138. 2. Gaudioso C, Listernick R, Fisher MJ, Campen CJ, Paz A, Gutamann DD. Neurofibromatosis 2 in children presenting during the first decade of life. Neurology. 2019;93:964–967. 3. Borofsky S, Levy LM. Neurofibromatosis: types 1 and 2. Am J Neuroradiol. 2013;34:2250–2251. 4. Shields CL, Mashayekhi A, Dai VV, Materin MA, Shields JA. Optical coherence tomographic findings of combined hamartoma of the retina and retinal pigment epithelium in 11 patients. JAMA Ophtalmol. 2005;123:1746–1750. 5. Yassin AS, Al-Tamimi ER. Familial bilateral combined hamartoma of retina and retinal pigment epithelium associated with neurofibromatosis 1. Saudi J Ophtalmol. 2012;26:229–234. 6. Bosch MM, Boltshauser E, Harpes P, Landau L. Ophtalmologic findings and long-term course in patients with neurofibromatosis type 2. Am J Ophtalmol. 2006;141:1068–1077. Sprenger et al: J Neuro-Ophthalmol 2022; 42: e591-e592 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.