124

Bilateral retinoblastoma in early infancySaiju R, Duwal S

Tilganga Institute of Ophthalmology, Kathmandu, Nepal

Abstract

Introduction: Retinoblastoma is the most common primary intraocular malignancy of childhood.It is usually diagnosed before the age of 5 years. In spite of its early onset in most children,retinoblastoma is rarely diagnosed congenitally or even within the first 3 months of life.Objective: To report a case of retinoblastoma in early infancy. Case: This was a case of theearliest presentation of retinoblastoma in a female child 20 days after birth. The presentingcomplaint was of leucokoria noticed by the mother 13 days after birth. The father of the childwas also found to have a suspicious lesion of retinocytoma in one eye and regressedretinoblastoma in the other eye. Conclusion: For early diagnosis of the disease, awarenessand knowledge about the modes of presentation of the disease are very important. Similarly,the ophthalmic examination of the parents and siblings with retinoblastoma should always bedone to exclude the disease.

Key-words: retinoblastoma, retinocytoma, phthisis bulbi

Saiju R et alBilateral retinoblastoma in early InfancyNepal J Ophthalmol 2013;5(9):124-128

Received on: 01.08.2012 Accepted on: 13.12.2012Address for correspondence: Dr Rohit Saiju, MDAssociate Professor, NAMS, Consultant OculoplasticSurgeon, Tilganga Institute of Ophthalmology, Kathmandu,Nepal.E-mail: rohitsaiju@gmail.com

Case report

IntroductionRetinoblastoma is the most common primaryintraocular malignancy of childhood and accountsfor about 3 % of all childhood cancer (Kanski,2007; American Academy of Ophthalmology,2008-2009). The median age at diagnosis isapproximately 12 months in children who havebilateral retinoblastoma and 24 months in those whohave unilateral disease. It affects boys and girls withequal frequency and has no known racialpredilection. Approximately 60-70% of cases areunilateral and 30-40% of those are bilateral(American Academy of Ophthalmology, 2008-2009). It is usually a sporadic condition. Only 6%have positive family history (American Academy ofOphthalmology, 2008-2009). In hereditary cases,the affected child usually, but not always, has multipletumors in both eyes. Transmission of the disease in

such families follows the rules of autosomal dominantinheritance (Yanoff et al, 2009). .

Retinoblastoma is caused by a mutation in the RB1gene, located on the long arm of chromosome 13at locus 14 (13q14). Both copies of the RB1 genemust be mutated in order for a tumor to form.

We here report a case of bilateral retinoblastomawith an early presentation, at the age of 20 days.To the best of our knowledge, this is probably theearliest diagnosed case of retinoblastoma in Nepal.

Case reportA 20-day-old female child from the south easternpart of Nepal was brought to our institute with thecomplaints of whitish pupillary reflex in the right eye(RE), which her mother first noticed when the babywas 13 days of age. There were no other ocularcomplaints. The baby was born full term viaspontaneous vaginal delivery in a hospital to a 26-year-old mother. Further inquiry revealed that herelder brother was diagnosed as a case of

125

retinoblastoma and died at the age of 28 monthsafter the 2nd cycle of chemotherapy.

On examination, the baby could fix light with botheyes (BE). The anterior segment was within normallimits on both sides. Indirect ophthalmoscopyrevealed a whitish mass in BE. Intraocular pressure(IOP) was digitally normal in both the eyes. Theultrasonography B scan showed a dome-shapedechogenic mass in BE, arising from the retinaextending into the vitreous cavity. In the right eye,the mass occupied almost the whole of the vitreouscavity. The A Scan showed a characteristic V-Ypattern with alternating high and low spikes. TheCT scan of the orbit showed a hyperdense masswith flecks of calcification in the posterior aspect ofthe vitreous of both globes.

Figure 3: CT Scan of orbit showing hyperdensemass with flecks of calcification in posterior aspectof the vitreous of both globesA detailed examination under general anesthesiarevealed a corneal diameter of 11mm X 11.5 mmand IOP of 12 mmHg in both the eyes.The anterior segment was within normal limits inboth eyes. On posterior segment examination, novitreous seeding was seen. In RE, a whitish tumormass occupying whole of the fundus was seen withdilated overlying vessels. In the left eye (LE), theoptic disc was pink and round with a well-definedmargin with the CDR 0.3:1. Multifocal elevatedwhitish tumors confluent to each other, measuringabout 6 X 7 disc diameter temporal to the discinvolving the macular area with overlying dilatedvessels, were also seen in the left eye.Enucleation of the right eye with 14 mm Acrylic ballimplant was done and in left eye photocoagulationwith a diode laser around the tumor was tried.The histopathological examination of the enucleatedeye showed a diffusely growing tumor, composedof small round cells with scant cytoplasm and ovalhyperchromatic moulded nuclei with the presenceof frequent true and pseudo-rossettes and focalareas of necrosis. The choroid, sclera, cornea andoptic nerve were free of tumor. With this information,a diagnosis of “well-differentiated retionoblastoma”was made.

Figure 1: Ultrasonography of the right eye

Figure 2: Ultrasonography of the left eye

B-scan showing echogenic mass in the vitreouscavity. A-scan showing V-Y pattern with alternatinghigh and low spikes.

Figure 4: Photomicrograph showing multipleFlexner-Wintersteiner rosettes (true rosettes). The

Saiju R et alBilateral retinoblastoma in early InfancyNepal J Ophthalmol 2013;5(9):124-128

126

halo-like cluster of cells in each rosette surrounds anearly empty appearing central lumen containing finecytoplasmic processes (Hematoxylin and Eosinstain, magnification 10x, low power).

Chemotherapy was then started. After completionof two cycles, the patient was again examined undergeneral anesthesia. The tumor mass in the left eyehad increased in sizeto occupy almost the whole ofthe fundus. As the tumor size was growing rapidlyand was not regressing despite chemotherapy, thesecond eye of the patient was also enucleated afterdiscussing with the parents as the life of the patientwas deemed more important. The patient alsounderwent a total of 6 cycles of chemotherapy.

Figure 5: after enucleation of RE and 2nd cycle ofchemotherapy

RE- Anophthalmic socket. LE- tumor mass withoverlying vessels, seen with naked eyes.

The parents were also examined and it was foundthat the father had a best corrected visual acuity of6/6 in the left eye and in the right eye there was noperception of light. He was on prosthesis of the righteye. He told us that according to his parents, hisright eye started to decrease in size at the age of 2years. On further examining the father, we found awhitish lesion measuring about the size of 4 - 5 discdiameters in supero-nasal quadrant of the left eyewith an area of some calcification in the centralportion of the tumor and areas of some chorioretinalatrophy surrounding the lesion. With these clinicalfindings, we assumed that the phthisis bulbi wasperhaps the result of spontaneous regression ofretinoblastoma and that the lesion of the left eyewas retinocytoma.

Figure 6: Fundus photograph of patient’s fathershowing superonasal quadrant of LE indicatingwhitish lesion measuring about the size of 4-5 discdiameters with area of some calcification in thecentral portion of the tumor and areas of somechorioretinal atrophy surrounding the lesion.

Both the baby and the father were kept on regularfollow up. The parents were explained about thedisease and the risk of the other child developingretinoblastoma was explained.

DiscussionIn spite of its early onset in most children,retinoblastoma is rarely diagnosed congenitally oreven within the first three months of life (Kanski,2007).

Here, we diagnosed retinoblastoma in a 20-day-old female which is probably the earliest diagnosedcase in Nepal.

Abramson et al stated that the most commonmanifesting sign of children with retinoblastomadiagnosed in the first month of life is family history(Abramson et al, 2002). Similarly, in our case,though the patient was brought to us due to whitepupillary reflex, the positive family history of herbrother, who died at the age of 28 months due tothe same cause, made the parents seek medical helpsoon after detecting leucokoria.

If the parents were aware of the disease, they wouldhave taken the first child to the hospital in early stageof the disease. However, very early diagnosis doesnot always guarantee vision, salvage of the globe,

Saiju R et alBilateral retinoblastoma in early InfancyNepal J Ophthalmol 2013;5(9):124-128

127

or patient survival since the diagnosis may not reflectan early stage of the disease. We could not saveboth the eyes of our patient as the tumor was veryadvanced and aggressive.

A family history of retinoblastoma is very important.Retinoblastoma was the first cancer to be directlyassociated with a genetic abnormality. So, theparents and siblings of patients with retinoblastomashould have screening ophthalmic examinations toexclude an unknown familial disease. On screeningophthalmic examination, we found the father of thepatient to have a phthisis bulbi (RE), which mightbe a regressed retinoblastoma, and also a suspiciouslesion of retinocytoma in the fellow eye.

Spontaneous regression in a retinoblastoma, thougha rare phenomenon, is also well documented in theliterature. Regression of retinoblastoma usually leadsto a phthisical eye. A study by Das has reportedthree cases of spontaneously regressedretinoblastomas in 140 eyes removed forretino-blastoma (Das, 1964).  Isola-ted cases ofphthisical eyes showing regressed retinoblastomahave been reported by other researchers too (Jainet al, 1968; Mehra et al 1965).

In the literature, retinocytoma and retinoblastomahave also been reported in different forms andassociations: in the same family, in a case withretinoblastoma in one eye and retinocytoma in thefellow eye, as two separate foci in the same eyeand in the parents of a child with retinoblastoma(Gallie et al, 1982; Singh et al, 2000; Balmer et al,1991; Lueder et al, 1995).

Based on the evidence documented in the literature,the father in our case was diagnosed with regressedretinoblastoma in the right eye and retinocytoma inthe left eye on the following grounds: presence ofphthisical eye, presence of calcified tumour in thefundus with a characteristic clinical picture, presenceof retinoblastoma in two children.

Management of retinoblastoma should be guidedby the objectives to save life, to retain anatomicalintegrity of the eye, to preserve vision, and to obtain

good cosmetic results (Goddara et al, 1999). Inour case we tried all possible measures to preserveat least the left eye but as the tumor size wasincreasing aggressively and could have threatenedthe life of the patient, the second eye too had to beenucleated without delay.

Genetic counseling is another important thing to beconsidered while treating retinoblastoma. Theparents of a child with retinoblastoma should havean ocular examination and genetic counseling andthe risk of the child’s siblings developingretinoblastoma should be clearly explained.

A child who has hereditary retinoblastoma is at riskfor developing trilateral retinoblastoma and othercancers. Similarly, most retinocytomas are stableand demonstrate no tendency to grow or metastasize(Singh et al, 2000). However, there is still a possiblechance of malignant transformation which stressesthe importance of close follow-up of the patient witha presumed diagnosis of retinocytoma. Hence, inthis case, both the father and the child should bekept in a long-term follow-up.

ConclusionAwareness and knowledge about the disease is veryimportant as it may lead to early diagnosis, whichmay save eyes and lives, though this is not alwayspossible as the earlier diagnosis does not alwaysreflect an early stage of the disease. Also, screeningophthalmic examination of the parents and siblingswith retinoblastoma should always be done toexclude the disease.

ReferencesAbramson David H, Du Ted T, Beaverson K

L (2002). Retinoblastoma in the first month of life.Archives of Ophthalmology; 120:738-742.

Balmer A, Munier F, Gailloud C (1991).Retinoma: Case studies. Ophthalmic PediatricGenetics; 12:131-7.

Das SP (1964). Some observations onretinoblastoma. Indian J Ophthalmol; 12, 128-131.

Saiju R et alBilateral retinoblastoma in early InfancyNepal J Ophthalmol 2013;5(9):124-128

128

Gallie BL, Ellsworth RM, Abramson DH,Phillips RA (1982). Retinoma: Spontaneousregression of retinoblastoma or benign manifestationof the mutation. Br J Cancer; 45:513-21.

Goddara AG, Kingstoma JE, Hungerfordb JL(1999). Delay in diagnosis of retinoblastoma: riskfactors and treatment outcome. Br J Ophthalmol;83:1320-1323.

Jain IS, Singh K (1968). Retinoblastoma inphthisis bulbi. Indian J Ophthalmol; 16:76-8.

Kanski JJ (2007). Clinical Ophthalmology.Ret inoblastoma. 6 th edit ion. Edinburgh:Butterworth-Heinermann : 542-552.

Lueder GT, Heon E, Gallie BL (1995).Retinoma associated with vitreous seeding. Am J

Ophthalmol; 119:522-3.

Mehra KS and Banerjee C (1965).Spontaneous regression of retinoblastoma. Br JOphthalmology; 49:381.

Shetlar DJ (2008). 2008-2009 Basic andClinical Science Course: Section 4: OphthalmicPathology and Intraocular Tumors (Basic andClinical Science Course 2008-2009) Publisher:American Academy of Ophthalmology.

Singh AD, Santos MC, Shields CL, ShieldsJA, Eagle RC (2000). Observations on 17 patientswith retinocytoma. Arch Ophthalmol; 118:199-205.

Yanoff M, Duker J S (2009). Ophthalmology.Retinoblastoma. 3rd Edition: 887-894.

Source of support: nil. Conflict of interest: none declared

Saiju R et alBilateral retinoblastoma in early InfancyNepal J Ophthalmol 2013;5(9):124-128