A CASE AT ONCO PATHOLOGY:
JULY’S EDITION
MEDULLOEPITHELIOMA
september 2024
History
A 2 years and 05 month old male child presented with fleshy growth in his right eye of 2 month duration, the size of the growth gradually increased within 2mo to attain its current size.
In association with the growth he has slight redness of the same eye.In addition he has had repeated episodes of fever a month prior to his current presentation for which he was taken to a pediatrician and was given antipyretics and iron supplementation. His fever subsided after that..
Ophthalmic examination
| OD | OS |
| V/A | Doesn’t fixed and follow | Fixes and follows |
| IOP | Difficult to measure | |
| EYELID AND LASHES | No eyelid abnormality | No eyelid abnormality |
| CONJUNCTIVA | Slightly injected | quite |
| CORNEA | clear | clear |
| ANTERIOR CHAMBER | There is white vascularized lesion filling anterior chamber temporally |
Investigations
CBC – non revealing
Ocular U/S
– clear vitreous
- Anterior mass arising from ? Anterior retina on ciliary body
Impression
– ? retinoblastoma arising from anterior retina
Brain CT
There is a small relatively well defined 9mm in largest diameter involving the right anterior globe anterior to the lens . ? medulloepithelioma
Histopathology – Right eye Medulloepithelioma, Malignant
Microscopic Description
Section shows enucleation specimens containing tubules and papillary rosettes of pseudostratified hyperchromatic columnar epithelium with variable delicate stromal elements. There are also retinoblastoma-like areas with Homer Wright- like rosettes. Mitosis is brisk
Gross Description
Right enucleation specimen, O-P 2.1cm,vertical 2.5cm,horizontal 2cm with attached 1cm/ 10mm long optic nerve, cornea 1.2x1cm. C/s; There is 0.5×0.3×0.3 cm whitish lesion in the anterior chamber between the cornea and the lens. Otherwise no retinal detachment or mass in the posterior chamber seen.A-1x(O-P with optic nerve),B-3(callot)
Case Discussion
Definition
Medulloepithelioma is an embryonal neuroectodermal derived tumor with an intraocular predilection for the non-pigmented ciliary epithelium (NPCE). Besides the ciliary epithelium, medulloepithelioma has been noted in the CNS and even orbit. Ciliary body medulloepithelioma is the most common tumor arising from the non-pigmented ciliary epithelium and second most common pediatric intraocular tumor behind retinoblastoma.
Etiology
Most intraocular medulloepithelioma occur sporadically and are not associated with congenital malformations or cytogenetic abnormalities. However, an association exists between medulloepithelioma and Pleuropulmonary Blastoma Family Tumor and Dysplasia Syndrome (PPB-FTDS) in about 5% of cases. This syndrome is associated with the DICER-1 gene, which is a member of the ribonuclease III family and is inherited in an autosomal dominant fashion. About 3% of DICER-1 positive patients will manifest a ciliary body medulloepithelioma]. Tumors associated with this mutation include cystic nephroma, pleuropulmonary blastoma, ovarian tumors and thyroid hyperplasia. DICER-1 mutations have been associated with a higher rate of retinal abnormalities. KMT2D may represent another somatic mutation mutually exclusive to DICER-1 implicated in ciliary body medulloepithelioma pathogenesis. Rare occurrences of medulloepithelioma in patients with retinoblastoma have also been reported, although the exact mechanism of the association remains to be elucidated
Risk factor
There are no large population-based studies on the incidence or prevalence of medulloepithelioma. The literature largely consists of isolated case reports and case series. The Armed Forces Institute of Pathology (AFIP) reported the largest case series consisting of 56 histologically proven cases of medulloepithelioma . They reported a range of age of presentation from 6 months to 41 years, with a mean age of 3.8 years. The typical reported age of presentation was between 2 to 10 years, with most cases manifesting within the first decade. However, there have been reports of isolated cases documented in adulthood. Based on the reports from AFIP and other case-series, there is no predilection towards any specific race or either gender. Zimmerman et al. reported comorbid persistent hyperplastic primary vitreous in up to 20% of cases.
Diagnosis
Diagnosis of Medulloepithelioma is based on ocular exam findings and ancillary testing. Definitive diagnosis is made by histopathological analysis of tissue samples.
Clinical features
Due to the slow-growing nature of medulloepithelioma, patients frequently do not experience symptoms until tumor size is clinically observable or large enough to induce secondary symptoms. Initial clinical findings may include decreased vision, elevated intraocular pressure (IOP), angle closure, leukocoria, and eye redness. Causes of visual loss include cataracts, lens subluxation, lens coloboma, retrolental membranes, or neovascular glaucoma.
The tumor can typically be found in the ciliary body on slit lamp exam or gonioscopy and appears whitish-pink with chalky calcified opacities . However, cases of these tumors arising from the optic nerve have been described. Multiple grayish-white areas of cartilage or cysts may be seen within the tumor. These cysts may dislodge and be observed floating in the anterior chamber or vitreous in up to 50% of patients. One characteristic early feature, a congenital lens notch, results from the absence of zonules adjacent to the tumor.
Other anterior segment findings include ectropion uveae, corectopia or iris neovascularization. Neoplastic tissue growing over the anterior hyaloid and the posterior lens capsule may form a vascular retrolental membrane present in up to 60% of patients. The body of the mass may also extend into the vitreous .
Medulloepithelioma may produce secondary effects such as unilateral cataracts and neovascular glaucoma, both of which may be seen in up to 50% of cases. Secondary glaucoma is almost always due to iris neovascularization and subsequent angle closure, but direct tumor invasion into the angle may serve as another mechanism. Medical treatment of secondary glaucoma should be prioritized over surgery until regression of the primary tumor is achieved.
Other less frequent masquerading manifestations include uveitis, hyphema, vitreous hemorrhage retinal detachment, and extraocular extension of the tumor. The presence of these features can often delay diagnosis of the tumor. Such delay may portend poor prognosis including orbital invasion, distant metastases and even death.
Presenting phenotype may differ between congenital and childhood presentations of ciliary body medulloepithelioma. Neonatal medulloepithelioma may present in more advanced stages with leukocoria, buphthalmos, larger posterior chamber mass, and elevated IOP. Childhood medulloepithelioma may demonstrate more neovascular features, secondary glaucoma, and lens subluxation with a ciliary body mass
Management
Enucleation is the standard therapy for advanced ciliary body medulloepithelioma. In cases with orbital involvement an extended enucleation or exenteration may be required. Local resection may be attempted for smaller tumors occupying less than 3-4 clock hours, but high rates of recurrence resulting in secondary enucleation have been previously reported. Other options for smaller tumors include cryotherapy or radiotherapy. Plaque brachytherapy has been used in small to medium sized tumors with some success. The process is shorter, and produces better outcomes than local resection. Standard external beam radiotherapy is less effective and has been used primarily as adjuvant therapy. Intracameral and intravitreal chemotherapy were shown to achieve tumor regression in one case report. In a case of orbital medulloepithelioma, an intraconal tumor was first treated with chemoradiation prior to resection, which avoided enucleation. The role of systemic chemotherapy remains to be fully explored in patients with medulloepithelioma, but a combination of vincristine, etoposide, and carboplatin has been reported in one case series to prevent recurrence and metastasis for advanced medulloepithelioma patients.
Prognosis
Given the rarity of the disease, there have been few studies on the long-term prognosis in these patients. Tumors that remain confined to the globe have excellent prognosis, with a 5-year survival rate of 90-95% after enucleation. Broughton and Zimmerman et al. reported tumor-related deaths in 4 of 33 patients (12%), all these deaths occurred in patients with malignant tumors demonstrating extraocular extension. Thus extraocular spread proves to be a major predictor of mortality in these patients. However, cases have been reported of successful management of patients with orbital extension and metastatic disease with adjuvant chemotherapy, radiotherapy and surgery.
References
1-Yanoff, M., & Duker, J. S. (Eds.). (2021). Ophthalmology (4th ed.). Elsevier.
2-Bowling, B. (2016). Kanski’s Clinical Ophthalmology (8th ed.). Elsevier.
3-Kanski, J. J. (2019). Clinical Ophthalmology: A Systematic Approach (8th ed.). Elsevier.
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