Sporadic Unilateral Retinoblastoma Research Articles

The association between maternal nutrient intake during pregnancy and the risk of sporadic unilateral retinoblastoma among offspring

Previous studies have associated maternal diet during pregnancy with the development of sporadic unilateral retinoblastoma (RB), but few studies have focused on the role of individual nutrients. The aim of this study is to investigate the association between maternal nutrient intake during pregnancy and the development of sporadic unilateral RB in the offspring.A modified food frequency questionnaire, with additional questions on supplement use, was completed via a phone interview. Cases were recruited from hospitals and controls were comprised of friends and relatives of the patient without a history of cancer. Overall, 168 sporadic unilateral RB cases and 145 controls were included in case-control study. We performed logistic regression to estimate odds ratios (ORs) and 95 % confidence intervals (CI), adjusting for child’s age, child’s sex, parental race/ethnicity, maternal education, total calorie intake during pregnancy, maternal age at birth, maternal smoking during pregnancy, pre-pregnancy body mass index, maternal weight gain during pregnancy, paternal age at birth, and maternal multivitamin use in the year before pregnancy.In the adjusted model, the interquartile (IQR) increase in vitamin A intake, which was measured in retinol activity equivalent (RAE; OR: 0.64, 95 % CI: 0.46–0.90), and vitamin D intake (OR: 0.62, 95 % CI: 0.42–0.91) significantly reduced the risk of sporadic unilateral RB.These findings suggest that a higher intake of vitamins A and D can be a protective factor for sporadic unilateral RB. Further analyses in consideration of multi-exposures such as parental occupational exposures are warranted to discover the complex etiology of sporadic unilateral RB. In addition, the role of nutritional epigenetics for how maternal nutrient intake influences the risk of sporadic unilateral RB in the offspring still needs to be explored.

Medical radiation exposure and risk of sporadic retinoblastoma.

While there is evidence that parental exposure to medical radiation is associated with increased risk of sporadic bilateral retinoblastoma in offspring, this association has not been confirmed. Additionally, the relationship between paternal and maternal exposures and sporadic unilateral retinoblastoma has not been fully investigated. Data were obtained from two large multicenter case-control studies of retinoblastoma. For the paternal analyses, 268 bilateral cases, 155 unilateral cases, and 358 controls were included. For the maternal analyses, 298 bilateral cases, 184 unilateral cases, and 404 controls were included. Logistical regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CI) to evaluate the associations between parental exposures to medical radiation and sporadic retinoblastoma, while adjusting for potential confounders. Paternal exposure to medical radiation was not significantly associated with sporadic bilateral retinoblastoma in offspring. However, increasing paternal exposure to gonadal radiation was associated with increased risk of unilateral retinoblastoma (P-trend=.03). Maternal history of upper and lower gastrointestinal (GI) series was associated with bilateral retinoblastoma (OR=1.9, 95% CI: 1.1-3.2 and OR=6.9, 95% CI: 2.9-16.4, respectively). However, there was no association between maternal exposure to medical radiation and unilateral retinoblastoma in offspring. Our investigation adds to the evidence that medical radiation exposure in fathers as well as mothers prior to pregnancy may increase the risk of germline alterations leading to the development of retinoblastoma in their offspring. However, our findings could point to a more complex etiological framework for this important pediatric malignancy.

Abstract 5039: Medical radiation exposure and risk of retinoblastoma: A report from the Children’s Oncology Group

Abstract Retinoblastoma, which results from mutations in the RB1 gene, is the most common intraocular malignancy in childhood. Approximately 10% of cases are familial, and the remaining cases (both bilateral and unilateral) are considered sporadic. Although little is known about the causes of sporadic cases, there is some evidence that parental exposure to medical radiation is associated with sporadic bilateral retinoblastoma in offspring. These findings, however, have not been confirmed. Further, the relation between medical radiation exposure and sporadic unilateral retinoblastoma has not been investigated. Therefore, we evaluated the role of medical radiation exposure on sporadic bilateral and unilateral retinoblastoma. Eligible patients were diagnosed with sporadic bilateral or unilateral retinoblastoma from 1998 to 2011 and treated at one of nine participating institutions. Controls were recruited from the friends and relatives of cases. Telephone interviews were conducted with parents to obtain information on demographic factors and exposures, including medical procedures prior to conception of the index child. Gonadal radiation doses were estimated utilizing PCXMC and ImPACT software. Logistic regression models were used to evaluate the associations between parental medical radiation exposure and retinoblastoma. In maternal analyses, there were 298 bilateral cases, 184 unilateral cases, and 404 controls. In paternal analyses, there were 268 bilateral cases, 155 unilateral cases, and 358 controls. We found that compared to mothers without medical radiation exposure, mothers who reported a lower gastrointestinal (GI) series were more likely to have a child who developed bilateral retinoblastoma (odds ratio [OR]=6.9, 95% confidence interval [CI]: 2.9-16.4). A similar association was observed for unilateral retinoblastoma though the confidence interval included the null (OR=2.8, 95% CI: 0.8-9.7). When evaluating gonadal dose, increasing maternal exposure was associated with bilateral retinoblastoma (P for trend=0.03). Further, compared to unexposed mothers, mothers in the highest dose category were more likely to have a child who developed sporadic bilateral retinoblastoma (OR=2.3, 95% CI: 1.4-4.1). Notably, the same trend was not observed for unilateral retinoblastoma. Transversely, increasing paternal gonadal dose was associated with unilateral retinoblastoma (P for trend=0.03) but not bilateral retinoblastoma. These results are in contrast to previously hypothesized patterns (i.e., that maternal exposure would be associated with unilateral retinoblastoma, whereas paternal exposure would be associated with bilateral retinoblastoma due to a de novo mutation in RB1 of paternal origin). Our findings could point to a more complex etiologic framework for this important pediatric malignancy. Citation Format: Omar Shakeel, Nelson Pace, Philip J. Lupo, Michael E. Scheurer, Arupa Ganguly, Greta R. Bunin. Medical radiation exposure and risk of retinoblastoma: A report from the Children’s Oncology Group [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 5039.

Genetic screening in Iranian patients with retinoblastoma.

PurposeThe most common intraocular tumor in childhood, retinoblastoma, is largely associated with mutations in the RB1 gene. In the most comprehensive RB1 screening in Iran, we evaluated the RB1 mutations in 106 patients with retinoblastoma, including 73 bilateral (heritable) and 33 unilateral (sporadic) cases.Patients and methodsMutations were identified using amplification refractory mutation system (ARMS) PCR and direct sequencing of the 27 coding exons of RB1 and multiplex ligation-dependent probe amplification (MLPA).Results and ConclusionWe found 33 (31%) and 64 (60%) patients with sporadic unilateral and bilateral retinoblastoma, respectively as well as 9 (8.5%) cases with hereditary bilateral retinoblastoma. In total, we identified 52 causative RB1 mutations in 106 patients (global mutation rate of 49%). Of the 52 patients, 48 (92%) had sporadic and familial bilateral and 4 (8%) had sporadic unilateral RB. Therefore, the detection rate of RB1 mutations was 66% (48/73) and 12% (4/33) in bilateral and unilateral cases, respectively. Mutations were classified as nonsense in 31 (60%), missense in 1 (2%), large deletion in 11 (21%), small deletion in the 7 novel (15%) and splice site mutation in 2 (4%) patients with RB. Of 31 nonsense mutations, 23 (74%) occurred in the 11 Arginine codons of the RB1. Seven mutations (13%) were novel, and 45 (87%) had been previously reported. Thirty-three mutations were single-base substitutions leading to 31 nonsense amino acid changes and 2 splice site mutations in introns 12 and 16 of RB1. The altered 3D model structures of the RB1 novel mutant proteins are also predicted in this study.

Pediatric second primary malignancies after retinoblastoma treatment.

Children with retinoblastoma carry a high risk to develop second primary malignancies in childhood and adolescence. This study characterizes the type of pediatric second primary malignancies after retinoblastoma treatment and investigates the impact of different treatment strategies and prognostic factors at presentation. All national patients treated for retinoblastoma at the German referral center with a current age of 6-27 years were invited to participate in a study to characterize late effects. Data on pediatric second primary malignancies were recorded from 488 patients. Ten developed a malignancy before the age of 18 years. For children with heterozygous oncogenic RB1 alteration (heritable retinoblastoma), the cumulative incidence to develop a second malignancy at the age of 10 years was 5.2% (95% CI 1.7; 8.7%). This results in an elevated risk for sarcoma (n = 4) (SIR 147.98; 95% CI 39.81; 378.87) and leukemia (n = 4) (SIR 41.38; 95% CI 11.13; 105.95). Neither the functional type of the RB1 alteration nor its origin showed a significant impact. Treatment modality influenced incidence, latency, and type of malignancy. Previous radiotherapy increased the risk for solid tumors and 3 of 91 children developed acute leukemia after chemotherapy. However, 2 of 10 malignancies were diagnosed in patients with heritable retinoblastoma but without previous chemotherapy or external beam radiotherapy. Screening for second primary malignancy is an important part of pediatric oncological follow-up in patients with heritable retinoblastoma. For patients with sporadic unilateral retinoblastoma, genetic information influences treatment decisions and allows tailoring of follow-up schedules.

Sporadic unilateral retinoblastoma or first sign of bilateral disease?

BackgroundA small number of children with unilateral retinoblastoma later develop retinoblastoma in the contralateral eye (metachronous bilateral retinoblastoma).MethodsWe analysed the clinical and genetic characteristics of children with sporadic unilateral retinoblastoma...

Identificación de tres nuevas mutaciones en el gen RB1 en pacientes con retinoblastoma esporádico en Colombia

Retinoblastoma is a childhood cancer of the retina originated by altered or null retinoblastoma protein (pRb) expression. Genetic alterations in both RB1 alleles in the retinal cells are required for the development of retinoblastoma. In the sporadic form, non-hereditary RB1 gene mutations take place in a single retinoblast cell, and are therefore only present in tumor DNA (somatic mutations). Sporadic retinoblastoma is primarily unilateral, lacks family history and has no risk of transmission to descendants. Genetic tests for detection of RB1 mutation has improved the identification of carriers and facilitated accurate genetic counseling.To identify mutations in the RB1 gene in Colombian patients with sporadic retinoblastoma by PCR-SSCP followed by sequence.Four patients with sporadic retinoblastoma were analyzed by PCR-SSCP, followed by DNA sequencing to identify variations in the RB1 gene.We identified five variations in RB1 gene: three new mutations (one germline and two somatic mutations), one new polymorphism and one already reported somatic mutation. Four mutations were found in three patients with unilateral retinoblastoma and one mutation was found in a patient with bilateral retinoblastoma. One of these was a germline mutation in a sporadic unilateral retinoblastoma that was not present in the parents or three siblings analyzed.Our results emphasize the importance of identifying mutations for genetic counseling and clinical management of sporadic retinoblastoma patients. Description of a new RB1 gene variant is interesting since there have been a small number of polymorphisms reported for this gene.

Identification of three new mutations in the RB1 gene in patients with sporadic retinoblastoma in Colombia.

Retinoblastoma is a childhood cancer of the retina originated by altered or null retinoblastoma protein (pRb) expression. Genetic alterations in both RB1 alleles in the retinal cells are required for the development of retinoblastoma. In the sporadic form, non-hereditary RB1 gene mutations take place in a single retinoblast cell, and are therefore only present in tumor DNA (somatic mutations). Sporadic retinoblastoma is primarily unilateral, lacks family history and has no risk of transmission to descendants. Genetic tests for detection of RB1 mutation has improved the identification of carriers and facilitated accurate genetic counseling. To identify mutations in the RB1 gene in Colombian patients with sporadic retinoblastoma by PCR-SSCP followed by sequence. Four patients with sporadic retinoblastoma were analyzed by PCR-SSCP, followed by DNA sequencing to identify variations in the RB1 gene. We identified five variations in RB1 gene: three new mutations (one germline and two somatic mutations), one new polymorphism and one already reported somatic mutation. Four mutations were found in three patients with unilateral retinoblastoma and one mutation was found in a patient with bilateral retinoblastoma. One of these was a germline mutation in a sporadic unilateral retinoblastoma that was not present in the parents or three siblings analyzed. Our results emphasize the importance of identifying mutations for genetic counseling and clinical management of sporadic retinoblastoma patients. Description of a new RB1 gene variant is interesting since there have been a small number of polymorphisms reported for this gene.

Two-Dose Exposure of Intra-arterial Chemotherapy for Group D Retinoblastoma

The authors present a case of group D unilateral sporadic retinoblastoma treated with only two intra-arterial chemotherapy cycles using melphalan, which resulted in tumor regression, resolution of subretinal fluid, and, most importantly, salvage of the life, and the eye.

Étude moléculaire du rétinoblastome dans la population algérienne. Recherche de mutations du gène Rb au niveau constitutionnel et tumoral

Inactivation of both alleles of the RB1 gene during normal retinal development initiates the formation of a retinoblastoma (RB) tumor. RB1 screening remains difficult, most of the alterations being unique and randomly distributed throughout the entire coding sequence. In this report, we present the results of a constitutionnal and tumoral RB1 analysis in Algerian population. The detection of RB1 gene deletion or mutation was performed by high performance liquid chromatography (HPLC) and sequence analyses in 21patients. Germline abnormalities were found in 2/21patients of sporadic unilateral retinoblastoma. The spectrum of germline and tumoral alterations included: three nonsense mutations; one mutation affecting splice site; one deletion and two polymorphisms. In general, for the 21patients with no family history of the disease, we have identified mutations in germinal level in two of them showing that it is a transmissible form of retinoblastoma in these two cases known to be sporadic. A total of two mutations have not been previously reported.

Risk assessment of recurrence in sporadic retinoblastoma using a molecular-based algorithm

Purpose: Most RB1 mutations are unique and distributed throughout the RB1 gene. Their detection can be time-consuming and the yield especially low in cases of conservatively-treated sporadic unilateral retinoblastoma (Rb) patients. In order to identify patients with true risk of developing Rb, and to reduce the number of unnecessary examinations under anesthesia in all other cases, we developed a universal sensitive, efficient and cost-effective strategy based on intragenic haplotype analysis.Methods: This algorithm allows the calculation of the a posteriori risk of developing Rb and takes into account (a) RB1 loss of heterozygosity in tumors, (b) preferential paternal origin of new germline mutations, (c) a priori risk derived from empirical data by Vogel, and (d) disease penetrance of 90% in most cases. We report the occurrence of Rb in first degree relatives of patients with sporadic Rb who visited the Jules Gonin Eye Hospital, Lausanne, Switzerland, from January 1994 to December 2006 compared to expected new cases of Rb using our algorithm.Results: A total of 134 families with sporadic Rb were enrolled; testing was performed in 570 individuals and 99 patients younger than 4 years old were identified. We observed one new case of Rb. Using our algorithm, the cumulated total a posteriori risk of recurrence was 1.77.Conclusions: This is the first time that linkage analysis has been validated to monitor the risk of recurrence in sporadic Rb. This should be a useful tool in genetic counseling, especially when direct RB1 screening for mutations leaves a negative result or is unavailable.

Ewing’s sarcoma as second malignancy following a short latency in unilateral retinoblastoma

Second malignancies, mostly in the form of bone sarcomas, are known to occur in hereditary retinoblastomas, which usually present with bilateral disease. Only 2 cases of Ewing’s sarcoma have been reported in the literature following sporadic unilateral retinoblastoma. A 5-year-old boy presented to our hospital with Ewing’s sarcoma of the right humerus (proven by biopsy and immunohistochemistry) following successful treatment of retinoblastoma of the left eye with enucleation and chemotherapy 2 years previously. He was treated with 2 cycles of chemotherapy followed by radiation therapy. At 15 months follow-up, the tumor had reduced in size and the child had a good functional outcome. The cumulative risk of second malignancies in retinoblastoma survivors is 32%. Ninety-eight percent of second malignancies occur in patients with bilateral retinoblastoma. Germ line mutations have been considered in sporadic tumors occurring bilaterally and multifocal unilateral sporadic tumors. Bone and soft tissue sarcomas are the most common second malignancies. Radiation therapy increases the risk of developing a second malignancy in the irradiated field. Unilateral retinoblastomas, which comprise the majority of retinoblastomas, are not immune from the development of second malignancies. Close follow-up of all retinoblastomas—even in the early period—can improve the outcome by facilitating the early detection and aggressive treatment of second malignancies.

Meningioma 40 Years after Radiation Therapy for Retinoblastoma: Genetic and Phenotypic Analysis, and Minireview of Literature

The authors present a case of 44-year-old Caucasian female diagnosed with meningothelial meningioma 40 years after radiotherapy for sporadic unilateral retinoblastoma. The genetic analysis of DNA from the meningioma revealed no oncogenic mutation in the RB1 gene. The analysis of meningioma cells by flow cytometry revealed the following immunophenotype: vimentin++ CD56+ GFAP- EGFR-. Intermediate intensities of Her-2/neu and Pgp expression were detected in a small percentage of tumour cells. Data suggest that the tumour was most likely induced by radiotherapy and did not arise as a second tumour as there was no hereditary predisposition to retinoblastoma.

Ki-67 cell proliferation in familial and in esporadic unilateral retinoblastoma: case report

Ki-67 is a nuclear protein that is expressed at all phases of the cell cycle except the resting phase. This study is a clinicopathologic observational case report that aims to report on the cell proliferation rates, as measured by the Ki-67 antigen, in two enucleated retinoblastoma eyes. One unilateral familial (mother with unilateral disease - patient 1) and one unilateral sporadic retinoblastoma (patient 2) patients were submitted to enucleation without previous treatment. The tumor cell proliferation rate was assessed by the Ki-67 antigen labeling index (stained cells / 100 cells) in five different fields of the tumor. Patient 1 was 23 months old and the tumor was exophytic with associated neovascularization of the iris; patient 2 was 6 years old and the tumor was endophytic with coarse vitreous seeds. Both enucleated eyes presented optic nerve with free surgical margins. Positive Ki-67 cell index in patient 1 varied from 75 to 90 (MD +/- SD: 79.5 +/- 6.61) and in patient 2 from 38 to 60 (MD +/- SD: 46.6 +/- 8.2). The familial retinoblastoma, besides the earlier age presentation, showed 45.8% more Ki-67 positive cells than the same stage sporadic one. This proliferation rate may explain the earlier presentation age of the tumor in the inherited disease.

Outcome of Eyes With Unilateral Sporadic Retinoblastoma Based on the Initial External Findings by the Family and the Pediatrician

Outcome of Eyes With Unilateral Sporadic Retinoblastoma Based on the Initial External Findings by the Family and the Pediatrician

Unilateral retinoblastoma, lack of familial history and older age does not exclude germline RB1 gene mutation

Conclusive identification of RB1 mutations in retinoblastoma is predicted to improve the clinical management of affected children and relatives. However, despite clear clinical benefits, RB1 screening remains difficult, most of the alterations being unique and randomly distributed throughout the entire coding sequence. In this report, we present the results of a constitutional RB1 analysis undertaken in our institution over the last four years. The detection of RB1 gene deletion or mutation was performed by Southern blot and sequence analyses in 73 patients (including three families with 2, 3 and 3 probands, respectively). Complementary constitutional chromosome and fluorescent in situ hybridization (FISH) analyses of RB1 gene were applied in cases where hereditary retinoblastoma was suspected despite negative detection. Altogether, germline abnormalities were found in 11% (4/36 patients) of sporadic unilateral retinoblastoma (median age, 21.5 months) and 86% (32/37 patients) of sporadic bilateral or positive familial history retinoblastoma (median age, 5 months). The spectrum of germline alterations found in 31 distinct families included 12 nonsense mutations (39%); 10 point insertions or deletions with frameshift (32%); 4 mutations and 1 deletion affecting splice sites (16%); 2 missense mutations (6%); and 2 large deletions (6%). A total of 15 mutations have not been previously reported. In this small series, splicing mutations were associated with bilateral disease whilst most of the frameshift mutations were identified in patients with an early age at diagnosis, bilateral disease or hereditary forms of the disease. This study confirms that screening for constitutional RB1 mutation should become an integral part of current management of any patient affected by retinoblastoma irrespective of the tumour laterality and familial background.

Constitutional and Somatic RB1 Mutation Spectrum in Nonfamilial Unilateral and Bilateral Retinoblastoma in India

An epidemiologic survey has indicated a comparatively high prevalence of retinoblastoma (Rb) in Asian countries. Recently, the development of preventive strategies in nonfamilial Rb has become a major goal. The present studies were designed for identification and characterization of constitutional and somatic RB1 gene mutations by conventional cytogenetics, fluorescent in situ hybridization (FISH) and polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP)-DNA sequencing. Of 34 patients 32 were nonfamilial and 2 were familial Rb. Maternal inheritance of del (13q14) was common. FISH was sensitive in detecting monoallelic RB1 deletion/deletion mosaicism as a first genetic hit in 20% of cases. Somatic and germline RB1 point mutations affected exons 3, 17, 20, and 21 and these were identified as novel mutations. Involvement of exon 20 as a predisposing mutation in sporadic unilateral retinoblastoma (URB) probably suggests the susceptibility of exon 20 to unknown etiologic factors in our population. A de novo RB1 deletion along with transmitted RB1 point mutation from an asymptomatic parent was identified as a unique predisposing RB1 mutation chimerism in a URB case that later evolved to bilateral retinoblastoma (BRB). The predisposing mutations such as del (13q), RB1 mono-allelic deletion and RB1 point mutation in sporadic Rb were de novo as well as transmitted mutations from asymptomatic/symptomatic parents. The RB1 mutation incidence was comparatively higher (25%) in nonfamilial Rb with emphasis on high prevalence in sporadic URB (18% versus 0%-9% in the literature series). The present studies demonstrated the efficacy of a multitechnique approach to detect various types of constitutional RB1 mutations such as RB1 deletion, deletion mosaicism, point mutation, mutation chimerism in patients of symptomatic/asymptomatic parents.

Outcome of eyes with unilateral sporadic retinoblastoma based on the initial external findings by the family and the pediatrician.

To evaluate the enucleation rate for children with unilateral sporadic retinoblastoma based on initial external findings detected by the family and the pediatrician. A retrospective, nonrandomized review was performed on 257 consecutive patients with unilateral sporadic retinoblastoma treated at a major ocular oncology center. Data were gathered regarding the initial external clinical finding noted by the family members, pediatrician, and ocular oncologist and then correlated with the final resulted in enucleation in 77%. Specifically, enucleation was necessary in 75% of patients with pediatrician-detected leukocoria, 46% of those with pediatrician-detected strabismus, and 86% of those with pediatrician-detected red eye, heterochromia, decreased visual acuity, or an unspecified eye problem. Enucleation was necessary in 81% of those patients in whom an ocular oncologist detected any external finding such as leukocoria, strabismus, red eye, heterochromia, or buphthalmos and in only 33% of those without external findings. Children with retinoblastoma who present with obvious external findings of leukocoria, strabismus, or red eye detectable by their family or pediatrician most often require enucleation. Children who manifest no obvious external findings can often avoid enucleation.

Electroretinographic changes in the inner retinal layers of the retained eyes of patients with sporadic unilateral retinoblastoma

Purpose: Examination of retinal function as measured by flash electroretinogram (ERG) including oscillatory potentials (OPs) and pattern electroretinogram (PERG) in a series of patients with unilateral sporadic retinoblastoma. Patients: Studies were undertaken in the retained eye (without clinical evidence of retinoblastoma) of 13 patients with sporadic unilateral retinoblastoma and in 13 healthy controls. Methods: Standard flash ERG including scotopic OPs and PERG recordings were performed in accordance with the International Society for Clinical Electrophysiology of Vision (ISCEV) standards. Results: Statistically significant differences between the studied and the control groups were observed with flash ERG (OP1 amplitude increase, p < 0.003; photopic flicker amplitude increase, p < 0.05) and PERG (P50 latency increase, p < 0.008). Conclusions: Inner retinal layer dysfunction may be a characteristic feature of individuals with unilateral sporadic retinoblastoma.

Is Screening for Primitive Neuroectodermal Tumors in Patients With Unilateral Retinoblastoma Necessary?

Retinoblastoma is the most common childhood intraocular tumor, occurring in 1 of 18,000 live births. Retinoblastoma may occur as a germinal mutation or a somatic mutation. Forty percent of retinoblastoma cases are caused by a germline mutation and include those patients with a positive family history of the disease. Children with hereditary forms usually have multifocal, bilateral retinoblastoma, whereas children with the somatic form have unilateral, unifocal disease. However, up to 15% of cases of sporadic unilateral retinoblastoma may be hereditary. It is important to recognize that this subgroup of unilateral patients remains at risk for the development of second tumors as well as second primary tumors of the intracranial midline, or “trilateral retinoblastoma.” We report a case of a 2-month-old child with unilateral retinoblastoma in whom pinealoblastoma subsequently developed.