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| ORIGINAL ARTICLE |
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| Year : 2019 | Volume
: 12
| Issue : 3 | Page : 156-159 |
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Neonatal retinoblastoma: A study of five cases
Swathi Kaliki, Sai Divya Jajapuram
Ocular Oncology Service, The Operation Eyesight Universal Institute for Eye Cancer, LV Prasad Eye Institute, Hyderabad, Telangana, India
| Date of Web Publication | 11-Oct-2019 |
Correspondence Address:
Dr. Swathi Kaliki
The Operation Eyesight Universal Institute for Eye Cancer, LV Prasad Eye Institute, Hyderabad - 500 034, Telangana
India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/ojo.OJO_176_2018
 Abstract | | |
PURPOSE: The purpose was to study the clinical features, treatment, and outcome of retinoblastoma (RB) in neonates.
METHODS: This was a retrospective study of five patients with RB detected in the 1st month of life.
RESULTS: The mean age at diagnosis of RB was 22 days (median, 24 days; range, 14–28 days). There were one female and four males with neonatal RB. Two patients had a known family history of RB, and the tumor was detected by routine fundus screening in these children. Two patients were brought in with complaints of leukocoria and one patient with complaints of red-eye. All patients had an intraocular tumor at presentation. Four patients had bilateral involvement, whereas only one had unilateral involvement. Based on the International Classification of Intraocular Retinoblastoma, the tumors were classified as Group A (n = 2), Group B (n = 3), Group C (n = 1), Group D (n = 1), and Group E (n = 2). Macular involvement was noted in 6 (67%) eyes. The primary treatment included systemic chemotherapy with/without focal treatment in all patients. One patient subsequently underwent secondary enucleation as the globe became phthisical. One child died while on treatment due to pneumonia secondary to chemotherapy-induced neutropenia. Of the four patients who completed treatment, globe salvage was achieved in 6 (86%) eyes over a mean follow-up period of 89 months (median, 92 months; range, 29–144 months).
CONCLUSION: Neonatal RB though rare, if detected early, has a favorable outcome of ocular and life salvage. Sporadic RB can occur in neonates, and a family history may not always be elicited.
Keywords: Eye, neonates, retina, retinoblastoma, tumor
How to cite this article:
Kaliki S, Jajapuram SD. Neonatal retinoblastoma: A study of five cases. Oman J Ophthalmol 2019;12:156-9 |
| Introduction | |  |
Neonatal tumors are rare with an incidence of one in every 12,500–27,500 live births in the United States of America and the United Kingdom and vary from 17 to 121/million live births in other countries.[1] Most of the neonatal tumors are benign soft-tissue tumors, and malignant tumors are uncommon constituting only 2% of childhood malignancies.[2],[3] In a study of 102 cases of neonatal cancers over a 60-year period, the three most common malignancies included neuroblastoma (47%), retinoblastoma (RB) (17%), and soft-tissue sarcoma (12%).[3]
RB is uncommon in neonates though RB is considered to be the most common intraocular malignancy in children.[4] Diagnosis of neonatal RB, especially in developing nations, is rare, and prenatal diagnosis is a rarity due to lack of awareness and genetic counseling. The incidence of neonatal RB ranges between 4% and 29%.[5] Herein, we present a case series of five patients diagnosed with RB in the 1st month of life and discuss their clinical features, treatment, and outcome.
| Methods | | |
Institutional review board approval was obtained for the study. A review of data pertaining to patients presenting with RB in the 1st month of life from January 2006 to December 2017 was performed. All patients with inadequate data and age beyond 1 month were excluded from the study.
The following clinical data were obtained for each patient: age at presentation, gender, laterality, family history, chief presenting complaint, grouping of the tumor at presentation according to the International Classification of Retinoblastoma (ICIoR), and location of the tumor. The treatment details were recorded. Outcome measures included tumor recurrence, globe salvage, secondary malignancies, systemic metastasis, and death.
| Results | | |
Five patients were diagnosed with neonatal RB during the study period constituting <1% of all RB cases. The details of all cases are listed in [Table 1].
Patient demographics
The mean age at diagnosis of RB was 22 days (median, 24 days; range, 14–28 days). Of the five patients detected with neonatal RB, four patients were male, and there was one female patient. Four among the five patients had bilateral RB at presentation while family history was evident in two of the five patients. One patient was diagnosed with unilateral RB, and there was no conversion to bilaterality during the follow-up period of 12 years.
Tumor features and classification
Routine fundus screening revealed RB in two children with a known family history of RB. Two patients were brought to the clinic with complaints of leukocoria and one patient presented with a congested eye. Of the five patients with RB in our series, nine eyes harbored the tumor. Based on ICIoR, they were classified as Group A (n = 2), Group B (n = 3), Group C (n = 1), Group D (n = 1), and Group E (n = 2). Macular involvement was noted in six (67%) eyes [Figure 1]. | Figure 1: A 20-day-old neonate with a known family history of retinoblastoma was detected to have (a) Group B tumor in the right eye and (b) Group A nonmacular multifocal tumors in the left eye during routine fundus examination (white arrows).(c) The macular tumor in the right eye shows Type 1 regression pattern with six cycles of intravenous chemotherapy, and (d) tumors in the left eye became flat scars following treatment with transpupillary thermotherapy
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Management
Intravenous chemotherapy (IVC) with vincristine, etoposide, and carboplatin (VEC) at intervals of 3 weeks for a total of six cycles was planned for all patients. Transpupillary thermotherapy and cryotherapy were used in patients with Group A and Group B tumors along with IVC.
Outcome
Tumor recurrences were noted in four eyes (44%) in the form of retinal tumor (n = 1) or subretinal seeds (n = 3). Subretinal seeds were managed by focal treatment while the patient with solid retinal tumor recurrence was restarted on IVC along with transpupillary thermotherapy. One patient with bilateral RB succumbed to neutropenia after receiving five doses of IVC. Of the four cases who completed treatment as planned, ocular salvage was achieved in six of the seven eyes (86%) over a mean follow-up period of 89 months (median, 92 months; range, 29–144 months). The mean duration of treatment-free interval was 77 months (median, 70 months; range, 25–141 months). Of the three cases with retained globe, best-corrected visual acuity in the least-affected eye was 20/50 or better in all cases. No secondary malignancies or metastatic RB was observed in this case series.
| Discussion | | |
RB usually manifests between the ages of 3 months and 3 years,[6] and only 7%–10% of RBs are diagnosed in the 1st month of life.[5] In our series, <1% of RBs were diagnosed in neonates. The diagnosis of neonatal RB maybe three times more frequent in developed countries compared to developing countries.[5] This difference could be attributed to increased awareness among parents about genetic transmission of the disease and importance of screening of neonates in developed countries compared to developing countries.
Most of the cases are diagnosed at the time of routine fundus screening at or immediately after birth in cases with a positive family history of RB. However, 28%–76% of cases with neonatal RB may be sporadic with no family history of RB.[3],[5],[7] Leukocoria in neonates may be presenting feature of RB in 13%–36% of patients, especially in those with no positive family history.[5],[7] In our series, two neonates with a known family history of RB were detected to have bilateral tumors during routine fundus screening. There was no known family history of RB in the other three (60%) cases suggesting the sporadic occurrence of RB. Two of these patients were brought in with complaints of leukocoria and had bilateral disease suggesting germline mutation, whereas one child had red-eye with secondary glaucoma on presentation and had only unilateral disease. Genetic testing would help to determine if the patient with unilateral disease also had germline mutation. However, genetic testing was not done in this patient.
Neonatal RB may be unilateral or bilateral on presentation. However, 90% of those presenting with unilateral RB eventually become bilateral before 6 months of age.[5],[7],[8] In a study of 46 children with neonatal RB, 26 (57%) had unilateral involvement, of which 22 (85%) eventually developed bilateral disease.[7] This is important in counseling the parents about the importance of regular fundus screening for early detection of tumor in the otherwise normal eye. In our series, 4 (80%) patients had bilateral disease on presentation, whereas one child had unilateral involvement. The child with unilateral RB did not develop tumor in the other eye over a follow-up period of 12 years.
Tumor presentation in neonates with bilateral RB is usually asymmetric with an advanced grouping typically evident in the presenting eye. Early age at diagnosis may not always imply the early stage of the disease. Those tumors in cases with positive family history detected by routine fundus screening in the 1st month of life and those detected through close monitoring after diagnosis of the first eye may have early-stage disease of ICIoR Group A or B tumors, whereas those presenting with leukocoria tend to have an advanced stage disease (ICIoR Group C or beyond). In our series, Group A or B was noted in five eyes, whereas Group C, D, or E was noted in five eyes. One case with a positive family history of RB was detected with Group C RB at 14 days of age in spite of early routine fundus screening. All cases presenting with leukocoria or redness had advanced tumors (Group D or E) in the eye with the chief complaint.
There is a strong correlation between the age at diagnosis and retinal topographic location of the tumor, which follows a centrifugal pattern.[9] Younger the child, more the chances of macular involvement. However, bilateral macular involvement is rare.[8] Thus, at presentation, most of the tumors detected in the neonates are located at the macula, and the subsequent tumors are always anterior to the first tumor and never at the fovea. In a study from Finland, 80% of neonates with a positive family history had macular involvement at least in one eye, and the subsequent tumor in the other eye did not involve the macula.[5] In another study of 12 neonates with familial RB from The Netherlands, 10 (83%) had macular involvement in at least one eye at presentation, one (8%) had bilateral macular involvement, one (8%) had extramacular tumor in both eyes, and none of the four eyes which developed tumor subsequently had macular involvement.[8] In our study, of the four neonates with bilateral RB, one patient had unilateral involvement of macula, two had bilateral macular involvement, and one patient had bilateral extramacular tumors. The patient with unilateral RB had a large tumor filling the globe and thus presumably involving the macula.
Berry et al. in their series of 72 infants with RB diagnosed at <6 months of age recommended the usage of low-dose chemotherapy with 50% reduction of the standard chemotherapy dose for the first cycle of chemotherapy along with omission of vincristine if the child was <2 months of age and reported a 100% survival rate when combined with a thorough serial monitoring of hematological profile.[10] In our series, low-dose chemotherapy was not used. A standard dose of chemotherapy with VEC was well tolerated by four neonates, and one child died due to chemotherapy-induced neutropenia and subsequent pneumonia.
The management of neonatal RB is challenging in spite of early diagnosis. This is related to inadequate response to chemotherapy owing to limited vascular supply to smaller tumors, low-grade tumors, increased chances of vitreous relapse, and frequent new tumors.[5] In our study, tumor relapse was noted in four (44%) eyes, but none displayed vitreous tumor relapse.
Globe salvage rates in neonatal RB vary from 79% to 92%.[5],[7],[8] In our series, globe salvage was achieved in 86% of cases. Patients with neonatal RB are at increased risk of second nonocular cancers in the irradiated field (9%),[7] trilateral RB (4%–5%),[7],[11] metastatic RB (0%–9%),[5],[7],[8] and death (0%–17%).[5],[7],[8] In our series, no patient underwent irradiation, and there was no evidence of second nonocular cancer, trilateral RB, or systemic metastasis over a mean follow-up period of 89 months (median, 92 months; range, 29–144 months). One child died in our series, but the death was related to the treatment complications rather than the tumor itself.
| Conclusion | | |
The overall prognosis of neonatal RB is gratifying if detected early and managed promptly. IVC is well tolerated in most of the cases and requires continuous monitoring of hematological parameters. Meticulous follow-up is indispensable to identify and treat the recurrences and subsequent development of new tumors.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Financial support was provided by the Operation Eyesight Universal Institute for Eye Cancer (SK) and Hyderabad Eye Research Foundation (SK), Hyderabad, India.
Conflicts of interest
There are no conflicts of interest.
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| 7. | Abramson DH, Du TT, Beaverson KL. (Neonatal) retinoblastoma in the first month of life. Arch Ophthalmol 2002;120:738-42. |
| 8. | Imhof SM, Moll AC, Schouten-van Meeteren AY. Stage of presentation and visual outcome of patients screened for familial retinoblastoma: Nationwide registration in the Netherlands. Br J Ophthalmol 2006;90:875-8. |
| 9. | Abramson DH, Gombos DS. The topography of bilateral retinoblastoma lesions. Retina 1996;16:232-9. |
| 10. | Berry JL, Jubran R, Lee TC, Murphree AL, Lee D, Kim JW. Low-dose chemoreduction for infants diagnosed with retinoblastoma before 6 months of age. Ocul Oncol Pathol 2015;1:103-10. |
| 11. | de Jong MC, Kors WA, de Graaf P, Castelijns JA, Moll AC, Kivelä T. The incidence of trilateral retinoblastoma: A systematic review and meta-analysis. Am J Ophthalmol 2015;160:1116-26. |
[Figure 1]
[Table 1]
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