Case Report

Retinoblastoma
By : Maskur Ramadhan S. Ked
M. Akbar Batubara S. Ked

Supervisor: dr. Yazid Dimyati

Sp.A (K)

Pediatric Department of H. Adam Malik General

Hospital
Medical School of North Sumatera University

Background
Retinoblastoma is the most common

intraocular tumor and the Seventh

most common solid tumor in childhood.
Occurring in approximately 1 in 15,000
live births in the United States.
Approximately 95 % before the age of
five.
The incidence is similar in boys and
girls and among blacks and whites.
bilateral in 30% ; < 12 months.

FAMILIAL
(Hereditary)

SPORADIC
(Non-hereditary)

85% bilateral, multifocal.

Unilateral, unifocal.

40% of all cases.

60% of all cases.

Present earlier.

Present later.

Children of the affected have 45% chance

of inheritance.

Children of the affected are normal.

Chromosomal anomaly is a germline

mutation.

Chromosomal anomaly is a somatic

mutation.

Relatives have a high risk of RB

development.

Relatives have a low risk of RB

development.

Increased risk for second malignancies

sarcomas, melanoma, and cancers of the
brain and nasal cavities.
Autosomal dominant with high
penetrance.

Pathogenesis:
Mutational inactivation of both alleles

of the retinoblastoma (RB1) gene.

On chromosome 13q14.
Encodes a nuclear protein that acts as
a tumor suppressor and cell cycle
regulator; checkpoint between G1 & Sphase.
Normal individual inherits two copies of
this gene one from each parent.

A "two-hit" model
Sporadic
retinoblastoma:
First hit occurs after conception
in utero or in early childhood in
retinal cells.
All cells in body are not affected
as germ cells are not involved.
Second somatic mutation results
in loss of other normal allele.

Hereditary retinoblastoma
Child starts with heterozygous
alleles (RB/RB+).
Only one mutation is required
to produce disease.
First hit occurs in utero in germ
cells before conception or is
inherited from a parent.
All cells of body affected.
Second hit occurs in any retinal
cell.

STAGING
The International Retinoblastoma Staging System
(IRSS) may be used for staging retinoblastoma
Stage 0
Thetumoris in the eye only. The eye has not been
removed and the tumor was treated without surgery.
Stage I
Thetumoris in the eye only. The eye has been removed
and nocancercellsremain.
Stage II
Thetumoris in the eye only. The eye has been removed
and there arecancercellsleft that can be seen only
with amicroscope.

 Stage III
StageIII is divided into stages IIIa and IIIb:
In stage IIIa,cancerhas spread from the eye totissues
around the eye socket.
in stage IIIb, cancer has spread from the eye to
lymph nodesnear the ear or in the neck.
Stage IV
StageIV is divided into stages IVa and IVb:
In stage IVa,cancerhas spread to thebloodbut not to the
brain orspinal cord. One or moretumorsmay have spread
to other parts of the body such as the bone orliver.
In stage IVb, cancer has spread to the brain orspinal cord.
It also may have spread to other parts of the body.6

Natural history & Prognosis:

If untreated:
Retinoblastoma grows to fill the
eye (within 6 months) and destroys the
internal architecture of the globe.
Metastatic spread usually begins
after six months. => BM, bone, cx LNs,
liver

Death occurs within a matter of

years

Diagnosis:
The diagnosis of retinoblastoma can
usually be made during a dilated
indirect ophthalmoscopic
examination that is performed under
anesthesia;
the characteristic finding
is a chalky, white-gray
retinal mass with
a soft, friable consistency

Presentations of retinoblastoma

Leukocoria (60%) Strabismus (20%)Secondary glaucoma

Anterior segment invasion Orbital inflammat.

Orbital invasion

To confirm the diagnosis:

Ocular U/S:
Demonstrates a mass more echogenic
than the vitreous on B mode.
Highly reflective intrinsic
echoes of fine calcifications
on A mode.
Accuracy 80 %.

computed tomography:
may demonstrate a solid
intraocular tumor with
characteristic intratumoral
calcifications.

 Magnetic resonance imaging

(MRI):
tumor size.
optic nerve involvement.
the presence of an associated
intracranial lesion Tri-lateral RB.
preferred in children younger than
one year of age avoid cancer risk that
increase with CT

CT
MRI

 if there is clear evidence of tumor

outside the eye, the full
metastatic evaluation should
be done:
Bone marrow examination
(aspiration and biopsy).
Lumbar puncture.
Bone scan.

Differential diagnosis of leukocoria

Congenital cataract

Unilateral or bilateral

Coats disease

Unilateral

Persistent hyperplastic Inflammatory cyclitic

membrane
primary vitreous

Unilateral

Unilateral or bilateral

Posterior pole toxocara Advanced retinopathy

of prematurity
granuloma

Unilateral

Always bilateral but

may be asymmetrical

Treatment
Goals of treatment:
Save life.
Preserve vision or salvage eye

(i.e. avoid enucleation).

Minimize any complications or side
effects of therapy.

Treatment options:
Enucleation & Exenteration.
EBRTx.
Local therapies:

Plaque RTx.
Laser photocoagulation.
Cryotherapy.
Thermotherapy.

Chemoreduction:

I.V.
Subcojunctival.

Chemotherapy.

Recent Treatment of Retinoblastoma

1. Small tumours

Laser photocoagulation

Transpupillary thermotherapy
Cryotherapy

2. Medium tumours
Brachytherapy

Chemotherapy
External beam radiotherapy

3. Large tumours

Chemotherapy followed by local treatment

Enucleation

4. Extraocular extension
External beam radiotherapy

5. Metastatic disease
Chemotherapy

Chemotherapy:
Retinoblastoma is a chemo-sensitive malignancy.
The most active agents are carboplatinand
vincristine with or without etoposide.
Indications:

Vision salvage and delay or avoidance of radiotherapy in

patients with bilateral disease.
Tumor shrinkage in patients with unilateral disease, good
vision, and a tumor that is too large for isolated local
therapy
Metastatic disease.
Risk factors identified after enucleation (ie, massive choroid
invasion or postlaminar involvement of the optic nerve).

Chemoreduction
Most retinoblastomas are large at the time
of presentation, so chemoreduction is
often used to reduce tumor volume
enhances the success of local therapies.
As initial treatment of retinoblastoma
improves the ocular salvage rate.
Most common chemoreduction regimen
contains carboplatin, vincristine, and
etoposide, given approximately every 4
weeks.

 Numerous studies have been published that

Show that chemotherapy is very effective in
globe salvage; (eliminating the need for EBRTx/enucleation)
in R-E group IIV eyes success rate: 85% of
treated patients by 5 years.
while proving to be significantly less successful
in more advanced disease Approximately
40% of group C and 70% of group D eyes failed
systemic chemotherapy alone.

Shields CL, Mashayekhi A, Demirci H et al. Practical approach to management of

retinoblastoma. Arch Ophthalmol 2004;122:729735.
Shields CL, De Potter P, Himelstein BP et al. Chemoreduction in the initial management
of intraocular retinoblastoma. Arch Ophthalmol 1996; 114:13301338.

Intra-arterial chemotherapy:

in a very recent prospective study To determine whethe

intra-arterial chemotherapy is safe and effective in
advanced
intraocular RB.
78 patients with were treated.
Catheterization of the ophthalmic artery and injection of
chemotherapy, usually melphalan (with or without topotecan(.
End-points: event-free (enucleation or radiotherapy) ocular
survival, and ocular and extraocular complications.
2-years results:
Ocular event-free survival rates were 70%.
81.7% for eyes that received intra-arterial chemotherapy as primary
treatment.
58.4% for eyes that had previous treatment failure with intravenous
chemotherapy and/or external beam radiation therapy.
There were no permanent extraocular complications.

Gobin YP, Dunkel IJ, Marr BP, et al. Intra-arterial chemotherapy for the management of retinoblastom
four-year experience. Arch Ophthalmol 2011; 129:732.

Follow-up
Long-term follow-up is best accomplished by
a multidisciplinary team.
Recurrence usually occurs with in 3 years.
The risk period for extraocular spread after
successful treatment is generally recognized
to be 12 to 18 months.
Long-term survivors should also be followed
for the development of second malignancies.
Routine CT or MRI scans and bone scans are
probably not necessary.

Case Report
Name : MN
Age : 3 years 11 months old
Sex : Male
Date of Admission : 02nd February 2015

Main Complaint: Eye looks like a cat eye

History: This main complaint is experienced by patients in
8 months ago, and had brought to treatment within 4
months ago to the regional hospital of Banda Aceh. History
of red eye (+) experienced by patients within 5 months
ago. Headache (+) patients experienced since 1 month
ago. at this point the patient is not in a state of fever.
History of previous illness: Patients had previously been
treated in regional hospitals of Banda Aceh and was
examined orbital CT scan with contrast, with the results of
the mass in the Vitreous Dextra with calcification.

 History of drugs
Nothing
Pregnant History
1st child in the family. Mother was 27 years old during
pregnancy. There is no history of fever, hypertension, diabetic
mellitus, and herbal medicine consumption.
Birth History
Spontaneous; attended by nurses; BW 2100 gram; cyanotic
(-). Abnormality at birth: (-)
Immunization History
Till date all type of immunization completed
(BCG, Polio, Measles, Hep B, DPT)
Feeding History
From birth till 9th Months Old : Breast milk + formula milk

Physical Examination
Generalized status
Body weight: 14 Kg, Body length: 94 cm
BW/age: z = < 0
BL/age : z = -2
BW/BL: z = 0
Interpretation : normal nutrition
Praesens status
Level of Consciousness: Compos Mentis, Blood pressure 110/60 mmHg, HR: 90 bpm, RR: 26 bpm, body temperature:
37oC,
body weight : 14 Kg, body length : 94 cm.
Anemic (-), Icteric (-), Cyanosis (-), Edema (-), Dyspnea (-).
Localized status
Head :
Eye:
Right eye : light reflex (-), ciliary injection (+), conjuctiva injection (+), white formation covering lower part of cornea.
Left eye : Light Reflex (+), Pupil 3mm
Conjuctiva palpebra inferior anaemic (-/-), sclera icteric (-/-).
Nose and ear: normal
Mouth: normal
Neck : Lymph node enlargement (-).
Thorax: Symmetrical fusiformis, Chest retraction(-)
HR : 90 bpm, regular, murmur (-),
RR: 26 x/i,regular, ronkhi (-/-)
Abdomen:
Soepel, normoperistaltic. Liver, spleen and renal were unpalpable.
Extremities:
Pulse 90 bpm, regular, adequate pressure and volume, warm acral, Capillary Refill Time < 3.
Urogenital:
Male, normal

Laboratory Findings on HAM Hospital ( 2nd February

2015), outgoing patient:

Laboratory Findings on HAM Hospital ( 2nd February

2015), outgoing patient:
Result Normal
Liver
Bilirubin Total 0.28 mg/dL <1
Bilirubin Direk 0,08 mg/dL 0-0.02
Fosatase alkali (ALP) 309U/L <449
AST/SGOT24U/L <38
ALT/SGPT 13U/L <41
Renal
Ureum 20.9 mg/dL <50
Creatinin 0.50 mg/dL 0.17-0.42
AsamUrat 4.7 mg/dL<7,0

THORAX X-Ray
Normal Cor
Normal Sinuseas dan
diafragma
Normal Hilus
Bronkovaskular
characteristic normal
Spot and Soft tissue are
not visible

Result: Cardiomegaly Not

Found , There are No
Imaging of Active-TB

CT SCAN
Result:
The Mass in
the Vitreous
Dextra with
calcification

 Working Diagnosis:
Retinoblastoma OD
Management:
Bed Rest
Diagnostic Planning:
Bone Marrow Puncture

Follow Up

Discussion

Discussion

Conclusion
The conclusion of this paper is:
A boy, 3 year 11 months old, diagnosed
with Retinoblastoma OD, which is
confirmed by the results of CT scan with
contrast.
The patient received :
Bed Rest
Bone Marrow Puncture
Plan for Chemotherapy