Malignant teratoid intraocular ciliary body medulloepithelioma in a 5-year-old male with corresponding somatic copy number alteration profile of aqueous humor cell-free DNA

Abstract

Background: Intraocular, ciliary body, medulloepithelioma (CBME) is a rare tumor of the nonpigmented ciliary body epithelium, typically presenting in childhood. We describe a case of CBME.

Materials and methods: Ocular examination and imaging guided diagnostic and treatment decisions. Aqueous humor (AH) liquid biopsy was collected from the affected eye at eventual enucleation. Whole genome sequencing (WGS) was employed to determine somatic copy number alterations (SCNA) in AH cell-free DNA (cfDNA). Tumor sample was analyzed using various assays to evaluate for oncogenic mutations and SCNAs. Histopathology determined diagnosis.

Results: A 5-year-old male with glaucoma and cataract in the left eye (OS) experienced worsening left eye pain and redness. There was no light perception OS and the eye was hypotonus. Anterior segment exam showed complete cataract and rubeosis iridis. Ocular B-scan ultrasound OS revealed an intraocular lesion with calcifications and retinal detachment. Orbital MRI suggested left globe hypercellularity. An infiltrative lesion involving the ciliary body was seen in the left eye on examination under anesthesia. Left eye enucleation was performed in the setting of pain, blindness, and tumor, with anterior chamber paracentesis for AH liquid biopsy collection. SCNA profile of AH cfDNA demonstrated loss of copy of chromosomes 4, 6, and 9. Tumor was negative for clinically significant mutations or SCNAs. Histopathology diagnosed malignant teratoid CBME.

Conclusions: We present a case of CBME and include the unique SCNA profile of AH cfDNA from the enucleated eye. This case suggests utility of AH liquid biopsy in distinguishing between differential diagnoses for intraocular mass lesions.

Keywords: Malignant teratoid medulloepithelioma; aqueous humor liquid biopsy; intraocular ciliary body medulloepithelioma; somatic copy number alteration profile.

Figure 1.

Color fundus photographs of the right (a) and left (b) eyes. The right eye photograph displays a normal posterior pole without evidence of tumor formation (scattered peripheral retinal tufts not seen). The left eye photograph highlights a white infiltrative lesion (black arrow) with internal vasculature nasally involving the ciliary body and eroding the iris root, as well as spherical seeding adjacent to the lens.

Figure 2.

A magnetic resonance image of the orbit (axial T1 post-contrast image) demonstrating multiple findings in the left globe, including detachment of the left retina with enhancing nodularity along its undersurface (white arrows) and adjacent to the lens (red arrows), with corresponding restricted diffusion suggestive of a hypercellular process. Additionally, the left lens appears asymmetrically enlarged, compatible with known cataract (green arrow), with mild flattening of the left posterior sclera.

Figure 3.

Ocular B-scan (a) and ultrasound biomicroscopy (b) images of the left eye obtained during an examination under anesthesia. Figure 3(a) demonstrates complete funnel retinal detachment with thickening of the retina (white arrow) and scattered foci of calcification. Figure 3(b) demonstrates a retinal based, dome shaped, intraocular lesion with scattered diffuse intralesional calcium involving the ciliary body nasally, measuring 12.71x4.76 mm.

Figure 4.

Chromosomal copy number alteration profile demonstrating the chromosomal losses that vary from a diploid cell with a full complement of chromosomes. Determined through analysis of cell-free DNA in the aqueous humor following primary enucleation, showing loss of copy of chromosome 4, 6, and 9.

Figure 5.

Pathologic specimen from the enucleated left eye. Figure 5(a) is a macroscopic examination demonstrating a partially cystic ciliary body (cb) tumor (T). Note the spherical cyst by the white cataractous lens and the funnel shaped retinal detachment with subretinal proteinaceous exudate. Figure 5(b) is a central section of the eye which shows the tumor (T) expanding from the ciliary body (cb) to the equator of the lens, with a retrolental thin neoplastic membrane (arrow) extending to the epiretinal surface and pulling the retina anteriorly. Histopathologic examination demonstrates the tumor (T) in front of the ciliary body (CB) focally invading the angle and inner sclera (arrow) with a neoplastic membrane (arrow heads) attached to the lens (L), as seen in Figure 5(c). The iris (i) has extensive anterior synechia to the cornea (C) secondary to neovascularization (Hematoxylin and Eosin, original magnification 1.25X). In Figure 5(d), the retina is totally detached and folded, pulled by the neoplastic epiretinal membrane (arrow heads) with a condensed vitreous (Hematoxylin and Eosin, original magnification 2X). Figure 5(e) is a closer view of the brain like heterologous areas with loose white matter like areas to the left and neuronal and oligodendrocytic areas with spheroid calcifications (Hematoxylin and eosin. original magnification 20X). Figure 5(f) displays the typical embryonic neuroepithelial rosettes and ductal component of medulloepithelioma in the left lower corner with large areas of calcification (*) in the brain like heterologous areas (Hematoxylin and eosin. original magnification 4X). The colloidal iron discloses the loose mesenchymal tissue rich in hyaluronic acid, as seen in Figure 5(g) (Colloidal iron. original magnification 40X). Figure 5(h) displays areas of malignant component showing diffuse growth of atypical cells with high N:C ratio, with mitosis and apoptosis. Note the pool of apoptotic cells on the top of the field (Hematoxylin and eosin. original magnification 40X).