Medulloepithelioma: A triad of clinical features.

BACKGROUND: Intraocular medulloepithelioma arises from the primitive medullary epithelium and is diagnosed at a median age of five years. This tumor most commonly appears as a white, gray, or yellow-colored ciliary body tumor. The growth of medulloepithelioma is slow and it is locally invasive. Poor vision and pain are the most common presenting symptoms. The most common clinical signs include cyst or mass in iris, anterior chamber or ciliary body, glaucoma, and cataract. CASE: A 22-month-old Caucasian female twin presented with leukocoria and poor vision in OS. Examination revealed normal findings OD and a mass in OS. Based on the clinical features of leukocoria, lens changes and a white cystic ciliary body mass in a young child, ultrasonographic, and transillumination features, the lesion was diagnosed as a non-pigmented ciliary epithelial medulloepithelioma. After enucleation, the diagnosis of malignant teratoid medulloepithelioma of the non-pigmented ciliary epithelium was confirmed. There was no evidence of tumor recurrence or systemic metastasis at three years follow-up.
CONCLUSION: Medulloepithelioma in a child can present as a clinical triad of leukocoria, lens changes, and a white cystic ciliary body mass.

Introduction

Intraocular medulloepithelioma arises from the primitive medullary epithelium, a derivative of the inner layer of the optic cup.[12345] This tumor most commonly appears as a white, gray, or yellow-colored ciliary body tumor.[2] In rare instances, it can also originate from the retina or optic nerve.[3] This childhood tumor is diagnosed at a median age of five years.[2] Histologically, it appears as a network of sheets and cords of neuroepithelial cells.[24] The growth of medulloepithelioma is slow and it is locally invasive.[12] Herein, we report a case of malignant teratoid medulloepithelioma presenting with a triad of leukocoria, lens changes, and a white cystic ciliary body mass in a young child.

Case Report

A 22-month-old Caucasian female twin presented with leukocoria and poor vision in the left eye (OS). Birth and family history were unremarkable. Visual acuity was fix and follow in the right eye (OD) and no fix or follow OS. Examination under anesthesia revealed normal findings OD and a mass in OS. Superotemporally OS, there was posterior synechiae of the iris overlying a gray-white ciliary body mass with slight sub-luxation of the cataractous lens and subtle lens notch [Figure 1a]. There was no evidence of iris neovascularization or glaucoma. Intraocular pressures were 22 mm Hg OD and 18 mm Hg OS. There was no view of the fundus OS secondary to dense cataract. Transillumination disclosed a focal 12 mm round ciliary body shadow superotemporally abutting the limbus [Figure 1b]. Ocular ultrasonography and ultrasound biomicroscopy displayed a solid, dome-shaped, 10 mm thick ciliary body mass with numerous intratumoral cysts [Figure 1c] and areas of calcification. There was no evidence of extrascleral extension. Based on the clinical triad of leukocoria, lens changes, and a white cystic ciliary body mass in a young child, ultrasonographic, and transillumination features, the lesion was diagnosed as a non-pigmented ciliary epithelial medulloepithelioma.

Figure 1

A 22-month-old Caucasian female with superotemporal vaguely visualized yellow-white ciliary body mass (white arrow) and subluxated cataractous lens (black arrow) in the left eye (a). Transillumination showing a focal shadow abutting the limbus from 12:00 to 3:30 meridian (b). Ultrasound biomicroscopy displaying a solid ciliary body mass with intratumoral cysts (white arrow) (c). Globe cut section showing the ciliary body mass with cysts (black arrow) and persistent hyaloid artery (white arrow) (d). Histopathology of the mass showing interlinking bands and cords of neuroepithelial cells with scanty cytoplasm, hyaline cartilage (black arrow), cystic areas (white arrow) (e) and Flexner-Wintersteiner rosettes (white arrow) (f)

After informed consent, enucleation was performed. Gross examination of the sectioned globe revealed a white mass arising from the ciliary body with multiple cystic areas. Patent hyaloid artery inserting into Bergmeister papillae over the optic disc was also noted [Figure 1d]. Histopathological examination revealed interlinking and interweaving bands and cords of neuroepithelial cells with scant cytoplasm in the bulk of the tumor [Figure 1e]. There were prominent foci of hyaline cartilage, an area of calcification, scattered rosettes, a few foci of sheet-like proliferation of neuroepithelial cells resembling retinoblastoma, and no extrascleral component [Figure 1f]. The diagnosis of malignant teratoid medulloepithelioma of the non-pigmented ciliary epithelium was confirmed. There was no evidence of tumor recurrence or systemic metastasis at three years follow-up.

Discussion

Intraocular medulloepithelioma arises from the primitive medullary epithelium, a derivative of the inner layer of the optic cup.[12345] This tumor most commonly appears as a white, gray, or yellow-colored ciliary body tumor.[2] In rare instances, it can also originate from the retina or optic nerve.[3] This childhood tumor is diagnosed at a median age of five years.[2] In a clinicopathologic study of 56 cases of intraocular medulloepithelioma by Broughton and Zimmerman, poor vision (41%) and pain (30%) were the predominant symptoms.[2] Leukocoria was the presenting sign in 18% of the cases.[2] The most common clinical signs included cyst or mass in iris, anterior chamber or ciliary body (56%), glaucoma (48%), and cataract (26%).[2] Many of these salient features were observed in our patient.

Glaucoma with medulloepithelioma is classically due to iris neovascularization. Broughton and Zimmerman found that 61% (11/18) of eyes with secondary glaucoma displayed histopathologic evidence of iris neovascularization.[2] Iris neovascularization and/or neovascular glaucoma in a child with a normal fundus examination is highly suggestive of an occult ciliary body medulloepithelioma.[15] Shields and co-workers studied 10 patients with ciliary body medulloepithelioma and noted the following lenticular changes: lens notch or coloboma (90%), lens subluxation (70%), cataract (60%), and retrolental neoplastic cyclitic membrane (60%).[5] They emphasized that lens coloboma could be the earliest clinical sign of medulloepithelioma, and, furthermore, any child with an unexplained retrolenticular cyclitic membrane could be harboring an occult ciliary body medulloepithelioma.[5] Intratumor cysts, another important feature suggestive of medulloepithelioma, is found in 60% of cases and are best distinguished on ultrasonography.[5] An interesting finding with medulloepithelioma is the presence of persistence hyperplasia of the primary vitreous (PHPV) in nearly 20% of eyes. In our case, the persistent hyaloid artery was evidence of PHPV.

Based on histopathological examination, medulloepithelioma can be classified as non-teratoid or teratoid, and benign or malignant.[2] The non-teratoid medulloepithelioma results from the proliferation of primitive medullary epithelium.[2] The teratoid medulloepithelioma shows heteroplastic elements of hyaline cartilage, rhabdomyoblasts, undifferentiated mesenchymal cells, or neuroglial cells in addition to the proliferation of the medullary epithelium.[12] Histopathologic criteria for malignancy include one or more of the following: Presence of areas composed of poorly differentiated neuroblastic cells resembling those of retinoblastoma with or without rosettes, sarcomatous areas resembling chondrosarcoma, rhabdomyosarcoma, or embryonal sarcoma, greater pleomorphism or mitotic activity, and invasion of uvea, cornea, and sclera with or without extrascleral extension.[2] Based on these features, approximately 66% of medulloepitheliomas show malignant changes, but rarely do they metastasize.[2]

The treatment of choice for medulloepithelioma is enucleation.[1235] Medulloepithelioma shows mild response to standard dose radiotherapy, but plaque radiotherapy with a dose of 4000 cGy or above remains an alternative for smaller tumors.[25] Local resection by partial lamellar sclerouvectomy can be considered for small circumscribed tumors (<3 clock hours) but is associated with possible tumor recurrence.[1235] In a study by Broughton and Zimmerman, 80% (8/10) of the patients displayed tumor recurrence after iridocyclectomy, ultimately requiring enucleation. In a study of ten patients by Shields and coworkers, four patients had enucleation as primary treatment and six patients were managed by local resection. All six patients that were managed by local resection (iridocyclectomy) as primary treatment developed tumor recurrence, requiring additional treatment of enucleation in four, exenteration in one, and cryotherapy in one patient.[5]

Intraocular medulloepithelioma with extraocular extension can metastasize to regional lymph nodes and distant sites and is associated with low mortality.[12] Extraocular extension is a key prognostic factor for tumor-related death.[235] Death occurs mostly in cases with orbit involvement or intracranial extension.[125]