RetinoblastomaBy : Maskur Ramadhan S. Ked

M. Akbar Batubara S. Ked

Case Report

Supervisor: dr. Yazid Dimyati Sp.A (K)

Pediatric Department of H. Adam Malik General HospitalMedical 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 & S-phase.

• Normal individual inherits two copies of this gene one from each parent.

A "two-hit" model

Sporadicretinoblastoma: 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.

STAGINGThe International Retinoblastoma Staging System (IRSS) may be used for staging retinoblastoma• Stage 0

The tumor is in the eye only. The eye has not been removed and the tumor was treated without surgery.

• Stage IThe tumor is in the eye only. The eye has been removed and no cancer cells remain.

• Stage IIThe tumor is in the eye only. The eye has been removed and there are cancer cells left that can be seen only with a microscope.

• Stage IIIStage III is divided into stages IIIa and IIIb:

In stage IIIa, cancer has spread from the eye to tissues around the eye socket.

in stage IIIb, cancer has spread from the eye to lymph nodes near the ear or in the neck.

• Stage IVStage IV is divided into stages IVa and IVb:

In stage IVa, cancer has spread to the blood but not to the brain or spinal cord. One or moretumors may have spread to other parts of the body such as the bone or liver.

In stage IVb, cancer has spread to the brain or spinal 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

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

Anterior segment invasion •Orbital inflammat. • Orbital invasion

Presentations of retinoblastoma

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 solidintraocular tumor withcharacteristic intratumoralcalcifications.

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

C T 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 leukocoriaCongenital cataract

Unilateral or bilateral Unilateral

Inflammatory cycliticmembrane

Persistent hyperplasticprimary vitreous

Unilateral or bilateral

Coats disease

Unilateral Unilateral

Advanced retinopathy of prematurity

Posterior pole toxocaragranuloma

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 Retinoblastoma1. 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 carboplatin and

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 I–IV 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.

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• Shields CL, Mashayekhi A, Demirci H et al. Practical approach to management of retinoblastoma. Arch Ophthalmol 2004;122:729–735.

• Shields CL, De Potter P, Himelstein BP et al. Chemoreduction in the initial management of intraocular retinoblastoma. Arch Ophthalmol 1996; 114:1330–1338.

Intra-arterial chemotherapy: in a very recent prospective study To determine whether 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.

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Gobin YP, Dunkel IJ, Marr BP, et al. Intra-arterial chemotherapy for the management of retinoblastoma: 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 : MNAge : 3 years 11 months oldSex : MaleDate 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 drugsNothing

• Pregnant History1st 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 HistorySpontaneous; attended by nurses; BW 2100 gram; cyanotic (-). Abnormality at birth: (-)

• Immunization HistoryTill date all type of immunization completed(BCG, Polio, Measles, Hep B, DPT)

• Feeding HistoryFrom birth till 9th Months Old : Breast milk + formula milk

Physical ExaminationGeneralized status• Body weight: 14 Kg, Body length: 94 cm• BW/age: z = < 0• BL/age : z = -2• BW/BL: z = 0• Interpretation : normal nutritionPraesens 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 statusHead :

• Eye: Right eye : light reflex (-), ciliary injection (+), conjuctiva injection (+), white formation covering lower part of cornea.

Left eye : Light Reflex (+), Pupil Ø 3mmConjuctiva 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 <1Bilirubin Direk 0,08 mg/dL 0-0.02Fosatase alkali (ALP)309U/L <449AST/SGOT 24U/L <38ALT/SGPT 13U/L <41

• RenalUreum 20.9 mg/dL <50Creatinin 0.50 mg/dL 0.17-0.42AsamUrat 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 RestBone Marrow PuncturePlan for Chemotherapy