Intraocular medulloepithelioma is the second most common primary malignant neoplasm in children. It is an embryonic tumor arising from the primitive medullary epithelium of the optic cup and characteristically presents as a nonpigmented ciliary body mass. Despite being congenital, owing to its slow growth, it generally presents between 6 months and 5 years of age. A rare case of ciliary body medulloepithelioma presenting with buphthalmos at birth at 37 weeks of gestational age is reported. The enucleated eye revealed focal extrascleral extension and the child subsequently manifested regional lymph node metastasis. This is the youngest case of ciliary body medulloepithelioma presenting in a neonate reported in the English literature.
A 2-day-old female infant presented with a history of white reflex and enlarged left eye noted at birth. The child was born premature at 37 weeks of gestational age and was systemically healthy. The right eye was normal. The left eye was buphthalmic with a horizontal corneal diameter of 15 mm and an intraocular pressure of 30 mm Hg. A fleshy, pink vascular mass filled two-thirds of the anterior chamber, obscuring further visualization of the anterior segment and the fundus (Figure 1A). There was focal hyphema in the inferotemporal quadrant (Figure 1A). Ultrasound B-scan with immersion revealed a dense dome-shaped calcified mass arising from the ciliary body with variegated echotexture and low to high internal reflectivity (Figures 1B–1C). Regional lymph nodes were not palpable. Computerized tomography scan showed an enlarged eye with a heterodense ciliary body mass with calcification (Figures 1D–1E). A clinical diagnosis of teratoid medulloepithelioma of the ciliary body with secondary glaucoma was made and enucleation was advised. The child was lost to follow-up examination and returned after 2 months for surgery. Apart from an apparent increase in the size of the mass and thin sclera inferotemporally, there was no change in the clinical picture. A focus of abnormal placoid fleshy, pink scleral discoloration was noted in the inferior aspect intraoperatively.
Figure 1. Malignant teratoid ciliary body medulloepithelioma. (A) A newborn with buphthalmos of the left eye with a vascular pink, fleshy mass in the anterior chamber and hyphema. (B) Immersion ultrasound B-scan showing a dome-shaped calcified mass in the ciliary body region with (C) low to high internal reflectivity. (D and E) Computed tomography showing a soft-tissue mass with calcification filling the anterior chamber in an enlarged eye.
Gross examination and whole eye mount localized the ciliary body mass in the inferior aspect with anterior chamber and choroidal extension. There was a focal extraocular extension corresponding to the clinically abnormal area noted during enucleation. Microscopic examination showed a cellular tumor arising from the ciliary body involving the choroid and sclera with focal extraocular extension (Figure 2A). The tumor had a biphasic pattern comprising epithelial and sarcomatoid components. The epithelial component comprised primitive appearing cells arranged mainly in a diffuse pattern along with cords and nests (Figure 2B). These cells were round with scant cytoplasm and hyperchromatic nuclei. Mitoses averaged 4 to 5 per high-power field. The sarcomatoid component comprising spindle-shaped cells arranged in interlacing fascicles was seen admixed with the epithelial component. These cells had moderate cytoplasm and elongated nuclei with blunt end (Figure 2C). Mitoses in these foci averaged 1 to 2 per high-power field. Foci of calcification and necrosis were observed. The primitive epithelial cells were immunoreactive for glial fibrillary acid protein (Figure 2D), vimentin (Figure 2E), and neuron-specific enolase (Figure 2F). The sarcomatoid cells stained positively for glial fibrillary acid protein and vimentin (Figures 2G–2H). Desmin was negative in both of the components. Ki-67 activity was approximately 25% (Figure 2I). Based on the histopathological and immunohistochemical features, a diagnosis of malignant teratoid medulloepithelioma with focal extraocular extension was made.
Figure 2. (A) Microscopy showing the epithelial component comprising of primitive round cells arranged in sheets, cords, and nests (hematoxylin–eosin, original magnification ×100). (B) Focal extrascleral spread of the tumor was observed (hematoxylin–eosin, original magnification ×100). (C) Sarcomatoid component comprising spindle-shaped tumor cells displaying nuclear atypia (hematoxylin–eosin, original magnification ×400). (D) Positive glial fibrillary acid protein (GFAP) staining in primitive cells (original magnification ×400). (E) Positive vimentin staining in primitive cells (original magnification ×400). (F) Positive neuron specific enolase (NSE) staining in primitive cells (original magnification ×400). (G) Positive GFAP staining in sarcomatoid component (original magnification ×400). (H) Positive vimentin staining in sarcomatoid component (original magnification ×400). (I) Nuclear staining for Ki-67 in primitive cells (original magnification ×400).
General physical examination, ultrasound abdomen, chest electromagnetic radiation, serum beta-human chorionic gonadotrophin, and alpha-fetoprotein levels were normal. Further management was discussed at the multispecialty Tumor Board, and in view of the undefined role of adjuvant radiotherapy and chemotherapy in an infant with focal extraocular extension, it was decided to closely observe. At the 6-month follow-up visit, parotid, submandibular, and anterior cervical lymph nodes were found enlarged. Computed tomography scan (Figure 3A) confirmed the clinical finding. However, the socket was free of local tumor recurrence. Fine needle aspiration cytology revealed a cellular aspirate composed of malignant, discohesive round cells suggestive of metastatic medulloepithelioma (Figure 3B). The child underwent radical neck dissection and 4,800 cGy fractionated external beam radiotherapy, and was well with no local tumor recurrence or systemic metastasis at 18 months of follow-up.
Figure 3. (A) Computed tomography of the neck showing enlarged intra-parotid lymph node. (B) Fine needle aspiration cytology of the lymph node showing discohesive malignant small round cells suggestive of metastasis (geimsa, original magnification ×100).
Ciliary body medulloepithelioma characteristically presents as a nonpigmented ciliary body mass.1,2 Fuchs noted the distinctive netlike pattern of interlacing cells and named it “diktyoma.” The term “medulloepithelioma” was first used by Grinker in 1931.3 Zimmerman later categorized it as teratoid or non-teratoid and benign or malignant.4 Broughton and Zimmerman reported the largest series of 56 cases.5
Cords of cells resembling medullary epithelium of the brain or embryonic retina is a characteristic feature of medulloepithelioma. Heteroplastic cartilage, brain, and muscle, and retinoblastic and rhabdomyomatous differentiation are common.1,2,5 Immunohistochemistry has confirmed its neuroepithelial, neuroblastic, and glial origin.1,5,6 A third of medulloepitheliomas demonstrate a teratoid component.5 Histologic criteria for malignancy include poorly differentiated neuroblastic cells, pleomorphism and/or mitotic activity, sarcomatous changes, and contiguous invasion or extrascleral extension.5 Shields et al. reported that 50% of tumors are teratoid and 90% are malignant.1
The mean age of presentation was 5 years in a series of nine cases, and the youngest child was 2 months old at the time of diagnosis.1 Our patient manifested the tumor at birth at the gestational age of 37 weeks, which is the youngest presentation to the best of our knowledge. Medulloepithelioma is typically unilateral and sporadic. Priest et al. suggested that medulloepithelioma might be associated with dysembryonic pleuropulmonaryblastoma with a germline mutation of the DICER1 gene, and may indicate a heritable predisposition.7 Our patient did not have a family history.
The diagnosis of medulloepithelioma is based on its typical clinical presentation with a fleshy vascular mass with “sago grain” cysts. Localized lenticular notch, subluxation, or cataract may be an initial presentation. Vascular retrolental cyclitic membrane is seen in 60% and is formed by the anterior vitreous face or the posterior lens capsule acting as a scaffold for the tumor cells to proliferate. Calcification is attributed to the heteroplastic cartilage or bone or dystrophic calcification.1
Misdiagnosis of medulloepithelioma as unilateral congenital glaucoma or cataract is common, especially when the tumor is not directly visualized, with consequent inappropriate intraocular surgery or delayed management.1,2,8,9 Immersion B-scan ultrasonography and computed tomography may help when the tumor is occult. Foster et al. considered highly reflective cystic ill-defined ciliary body mass on ultrasonography suggestive of medulloepithelioma.10 Ultrasound biomicroscopy or anterior segment optical coherence tomography may be useful.
Because medulloepithelioma is generally advanced at the time of diagnosis, enucleation is the treatment of choice.1,2,5,8 Local resection such as iri-docyclectomy has been attempted in smaller tumors with varying success.6 Shields et al. performed partial lamellar sclerouvectomy in six patients, but were able to retain the eye in only one patient.1
Ten of 56 cases reported by Broughton and Zimmerman had extrascleral extension.5 The unique feature in our case was the extrascleral extension at 2 months of age, demonstrating the aggressive behavior of the tumor. Regional lymph node metastasis 6 months later despite the absence of local tumor recurrence indicates micrometastasis before enucleation was performed.
If untreated, medulloepithelioma is locally destructive and has potential for systemic metastasis. The contributing factor to regional lymph node metastasis may be extraocular extension as indicated in our case. In the Armed Forces Institute of Pathology series, one patient presented with regional lymph node metastasis 2 years following enucleation that progressed to death.5 In an advanced malignant tumor with extraocular infiltration, orbital invasion, and intracranial extension, chemotherapy and external beam radiotherapy have been used with varying success.2,8,9 A recent report showed chemotherapy (vincristine, etoposide, and carboplatin) and radiotherapy to be effective in orbital medulloepithelioma with lymph node metastasis.8 Vishwanathan et al. used radiotherapy for three patients with orbital tumor and regional lymph node metastasis following exenteration but failed to prevent disease progression in two.9 Our patient underwent radical neck dissection and external beam radiotherapy for regional lymph node metastasis and is currently free of recurrence.
Medulloepithelioma of the ciliary body can present in a newborn with unilateral buphthalmos and glaucoma. A good clinical evaluation, ultrasonography B-scan, and computed tomography may help confirm the diagnosis. Enucleation is the treatment of choice for advanced tumors. Careful attention should be paid to histopathology for features of malignancy and extrascleral extension and adjuvant treatment may be individualized under such situations. Close follow-up examination may help detect and appropriately manage regional lymph node metastasis.
- Shields JA, Eagle RC Jr, Shields CL, Potter PD. Congenital neoplasms of the nonpigmented ciliary epithelium (medulloepithelioma). Ophthalmology. 1996;103:1998–2006.
- Saunders T, Margo CE. Intraocular medulloepithelioma. Arch Pathol Lab Med. 2012;136:212–216. doi:10.5858/arpa.2010-0669-RS [CrossRef]
- Grinker RR. Gliomas of the retina, including the results of studies with silver impregnation. Arch Ophthalmol. 1931;5:930–935. doi:10.1001/archopht.1931.00820060088009 [CrossRef]
- Zimmerman LE. Verhoeff’s “terato-neuroma”: a critical reappraisal in light of new observations and current concepts of embryonic tumors. Trans Am Ophthalmol Soc. 1971;69:210–236.
- Broughton WL, Zimmerman LE. A clinicopathologic study of 56 cases of intraocular medulloepitheliomas. Am J Ophthalmol. 1978;85:407–418.
- Kivelä T, Tarkkanen A. Recurrent medulloepithelioma of the ciliary body: immunohistochemical characteristics. Ophthalmology. 1988;95:1566–1575.
- Priest JR, Williams GM, Manera R, et al. Ciliary body medullo-epithelioma: four cases associated with pleuropulmonary blastoma: a report from the International Pleuropulmonary Blastoma Registry. Br J Ophthalmol. 2011;95:1001–1005. doi:10.1136/bjo.2010.189779 [CrossRef]
- Meel R, Chawla B, Mohanti BK, Kashyap S, Bakhshi S. Ocular medulloepithelioma chemosensitivity. Ophthalmology. 2010;117:2440. doi:10.1016/j.ophtha.2010.05.008 [CrossRef]
- Viswanathan S, Mukul D, Qureshi S, Ramadwar M, Arora B, Kane SV. Orbital medulloepitheliomas with extensive local invasion and metastasis: a series of three cases with review of literature. Int J Pediatr Otorhinolaryngol. 2008;72:971–975. doi:10.1016/j.ijporl.2008.03.026 [CrossRef]
- Foster RE, Murray TG, Byrne SF, et al. Echographic features of medulloepithelioma. Am J Ophthalmol. 2000;130:364–366. doi:10.1016/S0002-9394(00)00542-0 [CrossRef]