Medulloepithelioma

• Primitive neuroepithelial neoplasm arising from the nonpigmented ciliary epithelium
• Typically diagnosed in young children with an average age of six years
• Patients may present with decreased visual acuity, leukocoria, or new strabismus.
• Findings include a visible retrolental ciliary body mass, cataract with subluxation, and possible secondary glaucoma
• Histologically malignant but distant metastasis and mortality are rare; when mortality occurs, it typically results from intracranial spread rather than systemic metastases.

• The most significant ocular manifestation of DICER1 syndrome, occurring in approximately 3% of individuals with germline DICER1 mutations. Additionally,
• Retinal abnormalities are found in about 11% of DICER1 carriers, significantly higher than the 1.5% rate in controls.
• Prospective study of 103 DICER1 carriers, three patients (3%) had CBME, with two identified during routine examination despite having normal dilated eye exams within one year prior to diagnosis
• Both germline and somatic DICER1 mutations have been identified in CBME, with somatic mutations frequently occurring in the RNase IIIb domain

Beyond CBME, DICER1 carriers show a significantly increased rate of retinal abnormalities (11%) compared to family controls (1.5%). These include:

• Retinal pigment abnormalities (5.8%)
• Increased cup-to-disc ratio (4.9%)
• Epiretinal membranes (1.9%)
• Optic nerve abnormalities (1.9%)
• Drusen (1.9%)
• Retinitis pigmentosa (rare)

One patient showed optic nerve elevation in the setting of increased intracranial pressure of unclear cause. Despite these findings, most DICER1 carriers (97%) maintain visual acuity of 20/40 or better in both eyes.

Current recommendations suggest that children with germline pathogenic DICER1 variants, especially those younger than 10 years, should undergo annual dilated ophthalmic examination to screen for CBME, signs of increased intracranial pressure, and retinal pigment epithelium changes

1. DICER1 Syndrome: Characterization of the Ocular Phenotype in a Family-Based Cohort Study. Huryn LA, Turriff A, Harney LA, et al. Ophthalmology. 2019;126(2):296-304
2. DICER1 Tumor Predisposition. Schultz KAP, Stewart DR, Kamihara J, et al. GeneReviews®. Updated 2020 Apr 30
3. Somatic Mutations of DICER1 and KMT2D Are Frequent in Intraocular Medulloepitheliomas. Sahm F, Jakobiec FA, Meyer J, et al. Genes, Chromosomes & Cancer. 2016;55(5):418-27
4. Somatic DICER1 Gene Mutation in Sporadic Intraocular Medulloepithelioma Without Pleuropulmonary Blastoma Syndrome. Durieux E, Descotes F, Nguyen AM, Grange JD, Devouassoux-Shisheboran M. Human Pathology. 2015;46(5):783-7