Evidence of predisposing epimutation in retinoblastoma.

Retinoblastoma (RB), which represents the most common childhood eye cancer, is caused by biallelic inactivation of RB1 gene. Promoter hypermethylation is quite frequent in RB tissues but conclusive evidence of soma-wide predisposing epimutations is currently scant. Here, 50 patients who tested negative for RB1 germline sequence alterations were screened for aberrant promoter methylation using methylation-specific MLPA. The assay, performed on blood, identified a sporadic patient with methylation of CpG106, absent in parents' DNA. Bisulfite pyrosequencing accurately quantified CpG methylation in blood DNA (mean ∼49%) and also confirmed the aberration in DNA isolated from oral mucosa although at lower levels (mean ∼34%). Using a tag-SNP, methylation was demonstrated to affect the maternal allele. Real-time qPCR demonstrated RB1 transcriptional silencing. In conclusion, we documented that promoter methylation can act as the first "hit" in Knudson's model. This mosaic epimutation mimics the effect of an inactivating mutation and phenocopies RB onset.

Intra-arterial chemotherapy for retinoblastoma: the dosimetric impact.

PURPOSE: Purposes are (1) to measure main radiation parameters and (2) to propose a method to estimate the absorbed doses of internal organs starting from DAP values. Measuring the exposition of internal organs by repeated irradiations on an anthropomorphic phantom with the same settings used in vivo, we could establish correlations between (1) DAP and the dose recorded by a dosimeter placed along the X-ray beam entrance pathway; (2) the dose recorded by the same dosimeter and the absorbed dose in internal organs. METHODS: Forty-four consecutive patients (16 males, 28 females) (mean age 35.4 months) treated at our institution with IAC (216 procedures: 196 via the ICA and 20 into branches of the ECA) were included in this prospective study. IAC was divided into 5 phases. Fluoroscopic time, DAP, and ESD were measured. RESULTS: The mean DAP was 595 ± 445 cGy cm2 and the mean fluoroscopic time was 540 ± 403 s. ESD was on average 9.59 mGy (range 0.8-165 mGy). The absorbed dose was lower than 12.1 mGy in the left retina (the more exposed organ) in 75% of single treatments and lower than 25 mGy in 95% of treatments. In the cases of 3 and 6 sessions, the left retina of 75% of patients absorbed respectively less than 36.3 and 72.7 mGy, whereas the left retina of 95% of patients received less than 75.2 and 150.4 mGy. Other organs were less exposed. CONCLUSION: This paper describes a method of absorbed dose estimation providing ranges used clinically in a single practice and the basis for further prospective studies.

Diagnostic Accuracy of Intraocular Tumor Size Measured with MR Imaging in the Prediction of Postlaminar Optic Nerve Invasion and Massive Choroidal Invasion of Retinoblastoma.

Purpose To assess the correlation of intraocular retinoblastoma tumor size measured with magnetic resonance (MR) imaging in the prediction of histopathologically determined metastatic risk factors (postlaminar optic nerve invasion and massive choroidal invasion). Materials and Methods The ethics committee approved this retrospective multicenter study with a waiver of informed consent. The study population included 370 consecutive patients with retinoblastoma (375 eyes) who underwent baseline MR imaging, followed by primary enucleation from 1993 through 2014. Tumor sizes (maximum diameter and volume) were measured independently by two observers and correlated with histopathologic risk factors. Receiver operating characteristic curves were used to analyze the diagnostic accuracy of tumor size, and areas under the curve were calculated. Logistic regression analysis was performed to evaluate potential confounders. Results Receiver operating characteristic analysis of volume and diameter, respectively, yielded areas under the curve of 0.77 (95% confidence interval [CI]: 0.70, 0.85; P < .0001) and 0.78 (95% CI: 0.71, 0.85; P < .0001) for postlaminar optic nerve invasion (n = 375) and 0.67 (95% CI: 0.57, 0.77; P = .0020) and 0.70 (95% CI: 0.59, 0.80; P = .0004) for massive choroidal tumor invasion (n = 219). For the detection of co-occurring massive choroidal invasion and postlaminar optic nerve invasion (n = 219), volume and diameter showed areas under the curve of 0.81 (95% CI: 0.70, 0.91; P = .0032) and 0.83 (95% CI: 0.73, 0.93; P = .0016), respectively. Conclusion Intraocular tumor size shows a strong association with postlaminar optic nerve invasion and a moderate association with massive choroidal invasion. These findings provide diagnostic accuracy measures at different size cutoff levels, which could potentially be useful in a clinical setting, especially within the scope of the increasing use of eye-salvage treatment strategies. (©) RSNA, 2015 Online supplemental material is available for this article.

Transorbital anastomotic pathways between the external and internal carotid systems in children affected by intraocular retinoblastoma.

PURPOSE: It is well known that many anastomoses can join the external carotid system and the ophthalmic artery. However, their frequency has never been reported. Since they can be relevant for interventional radiologists operating in the orbit, we decided to illustrate and determine the frequency of the anastomoses that can be found in children. METHODS: A retrospective study of 443 angiographic procedures (via ophthalmic artery and/or external carotid artery) carried out on 97 children affected by intraocular retinoblastoma was made to investigate the arterial anatomy of 106 orbits. RESULTS: Anastomoses were observed in 44.33 % of orbits. However, their true frequency is likely much higher as the rate of visualization increased up to 91.11 % of orbits when the angiographic study was extended to the external carotid artery. In order of frequency we detected the following anastomoses: lacrimal artery-middle meningeal artery, lacrimal artery-anterior deep temporal artery, ophthalmic artery-middle meningeal artery, ophthalmic artery-facial artery, supraorbital artery-superficial temporal artery, supratrochlear artery-superficial temporal artery, supraorbital artery-middle meningeal artery, dorsal nasal artery-infraorbital artery, supraorbital artery-zygomaticoorbital artery, lacrimal artery-zygomaticoorbital artery. CONCLUSION: When properly searched, anastomoses between the ophthalmic artery and the external carotid artery are almost constant in children. Depending on the clinical scenario, they can represent dangers or valuable alternative routes for collateral circulations and intraarterial chemotherapy.

Identification of Intraorbital Arteries in Pediatric Age by High Resolution Superselective Angiography.

PURPOSE: Angiography is a powerful tool to identify intraorbital arteries. However, the incidence by which these vessels can be identified is unknown. Our purpose was to determine such incidence and which angiographic approach is best for the identification of each artery. METHODS: A retrospective study of 353 angiographic procedures (via ophthalmic artery and/or external carotid artery) carried out on 79 children affected by intraocular retinoblastoma was made to investigate the arterial anatomy in 87 orbits. For each intraorbital artery two parameters were calculated: the angiographic incidence, as the percentage of times a given artery was identified, and the visibility index, as the ratio between the angiographic incidence and the true anatomic incidence. RESULTS: All collaterals of the ophthalmic artery could be spotted. Most of them were identified with a high angiographic incidence; some of them were less easily identified because too thin or because frequently shielded. The visibility index paralleled the angiographic incidence of most arteries. However, the lacrimal and meningolacrimal arteries had a higher visibility index suggesting that their identification was more frequent than the angiographic incidence alone could suggest. Statistical analysis demonstrated that the lacrimal artery and some muscular branches had higher chances to be identified if the angiography of the ophthalmic artery was accompanied by the study of the external carotid system. CONCLUSION: This work provides an objective measure of how powerful angiography is to identify intraorbital arteries as well as useful references for professionals who need to operate in the orbit.

Alternated intra-arterial and intravitreal chemotherapy for advanced intraocular retinoblastoma: preliminary successful results without systemic chemotherapy.

To describe the efficacy of intravitreal chemotherapy (IViC) preceded by intra-arterial chemotherapy (IAC) for the treatment of advanced stage retinoblastoma. This non-comparative interventional case series retrospectively reviewed the medical records of six patients who presented within months of each other with unilateral retinoblastoma, Reese-Ellsworth stage Vb/D of ABC classification in the affected eye. After clinical and ophthalmoscopic evaluation, they underwent MRI to exclude local and CNS dissemination. The IAC was given to treat retinal masses and intravitreal injections to treat vitreous seeding. Patients had received two cycles (six infusions) of IAC, and from six up to ten melphalan injections into the vitreous, with an interval of 7-10 days between them. From one to four intravitreal injections were performed for partial remission or consolidation. No permanent complications of procedures have been reported. All patients underwent to bimonthly MRI examination, during treatment and every 3 months for 1 year after last injection, to exclude orbital dissemination. Successful control (100 %) of tumor masses and vitreous seeds was achieved in all cases at 12 months follow-up. Complications were posterior lens opacity, acute ischemic papillitis, partial CVR thrombosis, hypotonia (case 1), partial vitreous hemorrhage (case 4). No complications appeared in cases 2, 3, 5, and 6. No intraocular or orbital tumor recurrence or retinoblastoma metastases (follow-up range, 12-33 months) were observed. Sequential IAC and intravitreal melphalan for advanced retinoblastoma allowed to provide retinal and vitreous seed control.

Massive anterior chamber involvement after intra-arterial chemotherapy for retinoblastoma: ultrasound biomicroscopy and histopathology.

This case report highlights the usefulness of Ultrasound Biomicroscopy (UBM) in a case of retinoblastoma which showed massive anterior chamber involvement after treatment with intra-arterial chemotherapy. UBM was used to document tumour pseudohypopion, cells in the aqueous humor, implanted clusters of cells on the corneal endothelium, iris nodules, lens capsule deposits and ciliary body invasion. The UBM data, compared with the histopathologic analysis, performed on eye tissue, after enucleation of the affected eye, revealed a significant concordance. UBM may represent an important diagnostic tool in retinoblastoma, when the decision about enucleation of the eye must be made in the absence of histopathologic data.

Retinal Reactive Astrocytic Tumor and Astrocytic hamartomas in patient with Neurofibromatosis type 1: Case Report and Literature review.

INTRODUCTION: Neurofibromatosis type I, also known as Von Recklinghausen disease, is a common phakomatosis affecting 1 in 2500-3000 live births; it may be associated with several common ocular findings, including Lisch nodules, plexiform neurofibromas, optic pathway gliomas, retinal astrocytic hamartomas and choroidal nodules. CASE DESCRIPTION: This report illustrates clinical evidence of simultaneous presence of retinal reactive astrocytic tumor (RRAT) and two retinal astrocytic hamartomas (RAH) in a 15 y/o patient with NF1, referred to our attention because of an asymptomatic fundus mass in his right eye of recent onset. CONCLUSION: This case, in addition to considering NF1 as one of the ocular conditions associated with secondary RRAT, underlines the importance of early referral and continuous ophthalmological follow-up in preventing possible complications that could cause significant visual impairment in patients with NF1.

Unusual anterior and posterior segment features of coats disease.

PURPOSE: To report the clinical course and management of unusual anterior and posterior segment features of Coats disease and their relation to the age of the patients to increase the awareness towards these rare clinical features rarely described in the current literature. METHODS: A retrospective descriptive review of 45 eyes of 45 patients affected by Coats disease was conducted at the Retinoblastoma Referral Center and Ophthalmology Unit of the University of Siena in Italy analyzing data from 2000 to 2022. Medical records and images were revised to find some cases presenting unusual anterior and posterior segment features in patients affected by Coats disease.We identified therefore 4 unusual clinical conditions: retinal macrocysts, anterior chamber cholesterolosis, fovea-sparing Coats disease and secondary vasoproliferative tumor. RESULTS: Two patients presented with retinal macrocyst (2/45 = 4.4%), one with anterior chamber cholesterolosis (1/45 = 2.2%), two with fovea sparing Coats disease (2/45 = 4.4%) and one with vasoproliferative tumor associated (1/45 = 2.2%) for a total of six (6/45 = 13.3%) patients manifesting unusual anterior or posterior segment features in Coats disease. CONCLUSION: Unusual anterior and posterior segment features of Coats disease such as retinal macrocyst and anterior chamber cholesterolosis have been more frequently reported in younger children while fovea-sparing and vasoproliferative tumors have been more commonly described in older patients. Age is then a strong prognostic marker which allows to distinguish two different phenotypes of Coats disease: patients younger and older than 3 years old with more aggressive and milder phenotype respectively.

Analysis of aqueous humour proteins in patients with retinoblastoma.

BACKGROUND: To investigate aqueous humour protein composition from retinoblastoma patients. DESIGN: Prospective, hospital-based study. PARTICIPANTS: Eighteen retinoblastoma patients (Reese-Ellsworth stage V or ABC classification group E RB) undergoing ocular enucleation, and 10 normal subjects undergoing cataract surgery. Five of 18 patients presented with associated secondary glaucoma whereas 13 had no secondary glaucoma; 5 of 13 patients with no secondary glaucoma received chemotherapeutical treatment with melphalan. METHODS: Aqueous humour samples were collected by limbal paracentesis of the anterior chamber after ocular enucleation in patients and after the stab peripheral corneal incision in controls. Total protein concentration according to Bradford method and sodium dodecyl sulphate-polyacrylamide gel electrophoresis of the samples were performed. MAIN OUTCOME MEASURE: Aqueous humour protein concentration. RESULTS: Aqueous humour protein concentration was significantly higher in retinoblastoma patients than controls (P < 0.01); patients with secondary glaucoma presented the highest values (P < 0.05 vs. controls); patients treated with melphalan presented a significant decrease (P < 0.01) versus non-treated; controls did not significantly differ from treated patients. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis pattern in retinoblastoma patients who did not receive any treatment was very different either from treated or from controls. CONCLUSION: This study represents a preliminary step towards a more accurate two dimensional electrophoresis (2DE) pattern, which will be combined with mass spectrometry analysis to clarify the potential role of specific proteins in tumour development and progression; although these results suggest that aqueous humour protein pattern in retinoblastoma is characteristic, several aspects of the study are still under investigation.

Medulloepithelioma in newborn: Advanced clinical status.

We report three cases of congenital medulloepithelioma, which is an extremely rare clinical pattern of a tumor rare by definition. The aim of this study is to underline the clinical features of advanced medulloepithelioma in newborns.

Rescue intra-arterial chemotherapy in unilateral multirelapsed peripapillary retinoblastoma: Decision making and the role of MRI.

INTRODUCTION: In this case report we report our experience with rescue intra-arterial chemotherapy in a case of multi-relapsed peripapillary Retinoblastoma (RB) and the importance of high resolution MRI in detecting possible optic disc infiltration. CASE REPORT: In 2007, a 14 month-old caucasian girl was referred to our ocular oncology unit for leukocoria. Only left eye was interested, with a single mass of the posterior pole. Patient underwent six cycles of systemic chemotherapy and focal laser consolidation. Several relapses occurred during follow-up. Selective intra-arterial chemotherapy (SIAC) with Melphalan was performed and type IV remission was achieved. A new relapse occurred next to the optic disc. MRI was performed and we decided to try to save the globe with a rescue cycle of SIAC. CONCLUSION: MRI has demonstrated to be useful in decision making in RB, giving us a last chance to save the globe.

Very late orbital recurrence of choroidal melanoma four decades post enucleation.

Orbital recurrence of malignant choroidal melanoma is quite uncommon, occurring in about 3% of patients undergoing enucleation for large tumors. Orbital recurrences after more than 10 years from enucleation are even rarer. In literature, only few reports described orbital recurrence that occurred between 10 and 40 years after primary diagnosis. Herein we report a very late choroidal melanoma recurrence, 40 years post enucleation, of a 52 year-old female who had undergone left enucleation at the age of 12. She presented to our clinic for consultation in 2017, complaining of difficulty to contain the prosthesis, as well as, presence of small pigmented palpable nodules inferiorly in her anophthalmic socket. The patient was not aware of the medical condition which had lead to the enucleation. We requested her medical reports and detailed history through her family. We realized after reviewing her charts 40 years back, that her enucleation was due to malignant choroidal melanoma (CMM). Full screening was performed. After magnetic resonance imaging (MRI), that showed the presence of nodular masses in the anophthalmic socket, an excisional biopsy was performed. Histopathology confirmed the diagnosis of CMM (epithelioid and spindle cell type), supporting the hypothesis that residual melanoma cells may remain clinically dormant for long periods, even for decades. A literature review was performed in order to review similar cases and to understand and discuss multiple factors, which may explain this extremely delayed recurrence. To the best of our knowledge, this is the third case to be reported in the literature.

p53 Arg72Pro and MDM2 309 SNPs in hereditary retinoblastoma.

The tumor suppressor p53 and its negative regulator MDM2 have crucial roles in a variety of cellular functions such as the control of the cell cycle, senescence, genome stability and apoptosis, and are frequently deregulated in carcinogenesis. Previous studies have highlighted the contribution of the common functional polymorphisms p53 p.Arg72Pro and MDM2 309SNP to the risk of both common cancers and Li-Fraumeni syndrome. Their possible role in retinoblastoma has recently been addressed by Castéra et al, who however only studied the MDM2 309SNP. Here, for the first time, we analyzed both single nucleotide polymorphisms (SNPs) in a case-control study of 111 Italian hereditary retinoblastoma patients. We found a significant association of the p53 Pro/Pro genotype with the disease (odds ratio=3.58, P=0.002). The MDM2 309SNP showed a weak negative association of allele G that deserves further investigation. These findings further support the hypothesis that genetic variability of the p53 pathway contributes to the individual susceptibility to retinoblastoma, as shown for Li-Fraumeni syndrome and a variety of non-hereditary cancers.

The Addition of Topotecan to Melphalan in the Treatment of Retinoblastoma with Intra-arterial Chemotherapy.

PURPOSE: To evaluate the effect of adding topotecan to melphalan for the treatment of retinoblastoma using intra-arterial chemotherapy (IAC). DESIGN: Single-center, consecutive case series. PARTICIPANTS: All eyes treated with IAC at the University of Siena, Siena, Italy, from 2008 to 2019. METHODS: Eyes were treated via IAC with either melphalan monotherapy or melphalan plus topotecan. The characteristics and outcomes of these 2 groups were compared. MAIN OUTCOME MEASURES: The main outcome measure was globe salvage rate. Additionally, a complete summary of all adverse events for all eyes was compared between groups and included local, regional, and systemic events causing both transient and permanent effects. RESULTS: A total of 193 patients and 208 eyes were treated with IAC between April 2008 and October 2019. Melphalan alone (MA) was used to treat 44 patients and 50 eyes for a total of 191 procedures. The combination of melphalan plus topotecan (MPT) was used to treat 149 patients and 158 eyes for a total of 780 procedures. Groups were similar in terms of age at presentation. The MPT group included more advanced eyes (P < 0.001) and had shorter follow-up time (mean 47 vs. 120 months in the MA group, P < 0.001). The MPT group required less laser and cryotherapy after treatment (32% of eyes vs. 50% of eyes in the MA group, P < 0.001); there was no other difference in the number of adjuvant treatments required between groups. There was no difference in the number of acute adverse events, both systemic and local, between groups. There was no difference in the number of transient or permanent intraocular side effects between groups. Kaplan-Meier survival analysis estimated a better globe salvage rate in the MPT group (66%) compared with the MA group (58%, P = 0.05). CONCLUSIONS: In this case series, the addition of topotecan to melphalan did not alter the IAC side effect profile and may contribute to improved globe salvage.

Fovea-sparing coats disease: A rare clinical entity.

PURPOSE: To evaluate the rarity, clinical features and management of Coats disease characterized by fovea-sparing enhancing the importance of pediatric retinal screening and early management to maintain a good visual acuity. METHODS: Retrospective analysis of approximately 40 patients affected by Coats disease between 2000 and 2020 at the Retinoblastoma Referral Center and Ophthalmology unit of the University of Siena in Italy. RESULTS: Two patients with fovea sparing Coats disease were included. Both presented an extrafoveal Coats disease (stage 2A by Shields classification) when they were 5 and 6 years old respectively.They had no anterior findings and a presenting visual acuity of 20/20 reflecting the early stage and a milder phenotype of the disease which are indeed more likely to be found in patients older than 3 years at presentation.Both presented telangiectasia and retinal exudation in the affected eye. Standard Argon laser photocoagulation and subsequently Cryotherapy were performed in the telangiectatic retinal periphery of both patients obtaining an excellent control and regression of the disease. CONCLUSIONS: Careful pediatric retinal screening and early management are crucial to ensure a good visual prognosis in such an early feature of Coats disease as fovea sparing since this condition unfortunately tends to recall the physician's attention in more advanced stages.Due to the extremely poor number of articles regarding such a rare feature of Coats disease like fovea sparing, we report our experience.

Bilateral retinoblastoma and osteogenesis imperfecta, a very rare association: Two cases.

INTRODUCTION: This case report presents two patients affected by a very rare association of bilateral retinoblastoma and osteogenesis imperfecta. CASE REPORT: Two Caucasian males with familial history and clinical signs of osteogenesis imperfecta came to our attention for bilateral leukocoria. The ocular fundus examination revealed bilateral retinoblastoma. Proper therapies were dispensed in order to achieve full regression. Genetic counseling was performed. DISCUSSION: The primary role of genetics in retinoblastoma pathogenesis in widely known, and different genes have been identified. Osteogenesis imperfecta is a rare connective tissue disorders, caused by mutated genes encoding for collagen. The single gene defect in osteogenesis imperfecta type VI is Serpin Family F Member 1 (SERPINF1), a neurotrophic factor for the neuronal differentiation in retinoblastoma cells. The association of bilateral retinoblastoma and osteogenesis imperfecta could be the result of the mutation of a single gene playing a role in a hypothetical common pathway.

13q Deletion Syndrome Involving RB1: Characterization of a New Minimal Critical Region for Psychomotor Delay.

Retinoblastoma (RB) is an ocular tumor of the pediatric age caused by biallelic inactivation of the RB1 gene (13q14). About 10% of cases are due to gross-sized molecular deletions. The deletions can involve the surrounding genes delineating a contiguous gene syndrome characterized by RB, developmental anomalies, and peculiar facial dysmorphisms. Overlapping deletions previously found by traditional and/or molecular cytogenetic analysis allowed to define some critical regions for intellectual disability (ID) and multiple congenital anomalies, with key candidate genes. In the present study, using array-CGH, we characterized seven new patients with interstitial 13q deletion involving RB1. Among these cases, three patients with medium or large 13q deletions did not present psychomotor delay. This allowed defining a minimal critical region for ID that excludes the previously suggested candidate genes (HTR2A, NUFIP1, PCDH8, and PCDH17). The region contains 36 genes including NBEA, which emerged as the candidate gene associated with developmental delay. In addition, MAB21L1, DCLK1, EXOSC8, and SPART haploinsufficiency might contribute to the observed impaired neurodevelopmental phenotype. In conclusion, this study adds important novelties to the 13q deletion syndrome, although further studies are needed to better characterize the contribution of different genes and to understand how the haploinsufficiency of this region can determine ID.

Retinoblastoma Is Characterized by a Cold, CD8+ Cell Poor, PD-L1- Microenvironment, Which Turns Into Hot, CD8+ Cell Rich, PD-L1+ After Chemotherapy.

Purpose: To investigate the impact of chemotherapy (CHT) on human retinoblastoma (RB) tumor microenvironment (TME). Cases and Methods: Ninety-four RBs were studied, including 44 primary RBs treated by upfront surgery (Group 1) and 50 primary RBs enucleated after CHT (CHT), either intra-arterial (IAC; Group 2, 33 cases) or systemic (S-CHT; Group 3, 17 cases). Conventional and multiplexed immunohistochemistry were performed to make quantitative comparisons among the three groups, for the following parameters: tumor-infiltrating inflammatory cells (TI-ICs); programmed cell death protein 1 (PD-1) positive TI-ICs; Ki67 proliferation index; gliosis; PD-1 ligand (PD-L1) protein expression; vessel number. We also correlated these TME factors with the presence of histological high-risk factors (HHRF+) and RB anaplasia grade (AG). Results: After CHT, a decrease in both RB burden and Ki67 positivity was observed. In parallel, most subsets of TI-ICs, PD-1+ TI-ICs, gliosis, and PD-L1 protein expression significantly increased (P < 0.001, P = 0.02, P < 0.001, respectively). Vessel number did not significantly vary. Age, HHRFs+ and AG were significantly different between primary and chemoreduced RBs (P < 0.001, P = 0.006, P = 0.001, respectively) and were correlated with most TME factors. Conclusions: CHT modulates host antitumor immunity by reorienting the RB TME from anergic into an active, CD8+, PD-L1+ hot state. Furthermore, some clinicopathological characteristics of RB correlate with several factors of TME. Our study adds data in favor of the possibility of a new therapeutic scenario in human RB.

Growth of congenital malignant teratoid medulloepithelioma of the ciliary body: a case study.

The purpose of this study was to describe the growth pattern of congenital malignant teratoid medulloepithelioma of the ciliary body by reporting clinical and imaging findings with pathological correlation. An 11-month-old little girl presented with a whitish-pink iris mass in the right eye resulting from a small ciliary body mass consistent with medulloepithelioma at both clinical and computed tomography (CT) findings. At CT, the lesion showed heterogeneous attenuation, without intraocular calcifications. Eleven months later, clinical and ultrabiomicroscopy showed a clear enlargement of the mass, which invaded the pupil. At magnetic resonance imaging (MRI), the lesion showed T1-weighted hyperintensity and T2-weighted slight hypointensity when compared to the vitreous and a notch in the anterolateral aspect of the ipsilateral lens. After intravenous gadolinium administration, the lesion showed intense homogeneous enhancement, and there was leakage of gadolinium in the anterior chamber, resulting from impairment of blood-aqueous barrier. Biopsy revealed a malignant teratoid medulloepithelioma. The eye was then enucleated, and histology confirmed the diagnosis. Systemic chemotherapy and radiotherapy were not performed, since there was no extraocular extension. The 57-month clinical and MRI follow-up did not show disease relapse. This uncommon case displays the natural history of congenital malignant teratoid medulloepithelioma of the ciliary body. While the tumour might have been successfully treated by local excision at diagnosis, the delay in surgical treatment led to tumour overgrowth with consequent need for enucleation. The most important prognostic feature is extraocular extension, which carries a risk of local recurrence, eventually resulting in intracranial extension and/or lymphatic spread.