RETINOBLASTOMA

Presented by OPIYO AUGUSTINE.

 Outline
• Introduction

• Epidemiology

• Pathogenesis

• Clinical presentations

• Diagnosis

• Differentials

• Treatment

• Prognosis
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 Introduction
• Is an Embryonal malignancy of the retina

• Originating from neuronal progenitor cells[can give rise to either neurons or glial tissue]

• The most common intraocular tumor in children.

• Its due to a defect in the RB1 gene

• Retinoblastoma accounts for 4% of all pediatric malignancies.

• The median age at diagnosis is approx 2 yr, and >90% of cases are diagnosed in children
younger than 5 yr of age.

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 Epidemiology
• In Uganda the incidence rate reported was 9000 new cases per year which corresponds to 1 in 15000
births.in a 10 year study between 2006 and 2015 at a tertiary hospital Mulago national referral hospital in
Kampala

• Majority of children with retinoblastoma in uganda clinically present with leucokoria and theres significant
delay in seeking treatment After diagnosis which results into poor prognosis.

• Overall, 66–75% of children with retinoblastoma have unilateral tumors, with the remainder having
bilateral retinoblastoma.

• Bilateral involvement is more common in younger children less than 1yr.

• Retinoblastoma can be either hereditary or sporadic.

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 PATHOGENESIS
• RB1 gene encodes the retinoblastoma protein, a tumor-suppressor protein that controls cell-
cycle phase transition[G1/S phase] and has roles in apoptosis and cell differentiation.[inhibits
transcription factor E2f when hypophosphorylated when active].

• Inactivation of retinoblastoma protein is found in retinoblastoma[hyperphosphorylation]

• Development follows the knudsons two hit hyposthesis,which states that both alleles of a
tumor suppressor gene must be mutated for phenotypic change to occur.

• In sporadic the first and second chnges occur later on in life

• In hereditary on the first hit is usually inherited and the second hit occurs later in life.

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 PATHOGENESIS
• Hereditary cases usually are diagnosed at a younger age and are multifocal and bilateral.

• Usually 40% of cases ,and they have a ridk of other tunors like osteosarcoma

• Trilateral retinoblastoma[ b/l retinoblastoma +peaniloblastoma]

• sporadic cases are usually diagnosed in older children, who tend to have unilateral,
unifocal involvement.

• Occurs when both Rb1 alleles are lost for phenotopic change

• Responsible for 60% of the cases

• Hereditary (younger age) and sporadic (older children)

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 Clinical Manifestations
• Classic – leukocoria, a white pupillary reflex (“cat eye reflex”)

• Strabismus

• Advanced disease

• Decreased vision

• Orbital inflammation

• Hyphema

• Pupil irregularity

• Pain can occur if secondary glaucoma is present.

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Clinical Manifestations
Retinoblastoma 10
 Diagnosis
• The diagnosis is established by the characteristic ophthalmologic findings of a chalky, white-
gray retinal mass with a soft, friable consistency.

• Imaging studies are not diagnostic, and biopsies are contraindicated.

• Indirect ophthalmoscopy with slit-lamp evaluation can detect retinoblastoma tumors.[can

differentiate between diffuse,exophytic and endophytic]

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 Diagnosis

• Orbital ultrasonography, CT, or MRI is used to evaluate the extent of intraocular

disease and extraocular spread.

• MRI allows for better evaluation of optic nerve involvement.

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 MORPHOLOGY
• Grossly,they are nordular masses usually in the posterior retina with satellite seedings

• microscopically, retinoblastoma appears as a small, round, blue cell tumor with rosette
formation (Flexner-Wintersteiner rosettes ).

• It may arise in any of the nucleated layers of the retina and exhibit various degrees of
differentiation.

• Retinoblastoma tumors tend to outgrow their blood supply, resulting in necrosis and
calcification.

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 Differential diagnosis
• Persistent hyperplastic primary vitreous
• Vitreous hemorrhage
• Cataract
• Endophthalmitis from Toxocara canis
• Retinopathy of prematurity
• Familial exudative vitreoretinopathy

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 MANAGEMENT
• Determinants
• Size and location of the tumors
• Disease localization (eye or spread to the brain or rest of the body)
• Hereditary or sporadic disease
• Goals
• Primary: cure
• Secondary: preserving vision and the eye, and decreasing the risk of late side
effects, mainly secondary malignancies

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 MANAGEMENT
Forms of treatment;
• Focal therapy; laser photocoagulation, transpupillary thermotherapy,
cryotherapy, plaque brachytherapy.
• Local therapy; external beam radiotherapy
• Chemotherapy; use agents like vincristine, etopiside and carboplatin
• Primary enucleation; for advanced unilateral tumors
 MANAGEMENT

• Most unilateral disease presents with a solitary, large tumor.

• Enucleation is performed if useful vision cannot be salvaged.

• With bilateral disease, chemoreduction in combination with focal therapy (laser

photocoagulation or cryotherapy) .

• Larger tumors often respond to multiagent chemotherapy , including carboplatin,

vincristine, and etoposide given intravenously.
 MANAGEMENT

• If these approaches fail, external beam irradiation should be considered.

• Brachytherapy , or episcleral plaque radiotherapy, is an alternative with less

morbidity.

• Enucleation may be required for unresponsive or recurrent tumors.

 MANAGEMENT

• Chemo reduction + focal therapy (laser photocoagulation or cryotherapy)

• Multiagent chemotherapy (carboplatin, vincristine, and etoposide) – Larger

tumors

• External-beam irradiation – chemo fails

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 MANAGEMENT

• Brachytherapy, or episcleral plaque radiotherapy, is an alternative with less

morbidity

• Enucleation – unresponsive or recurrent tumors.

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 Prognosis

• 95% cure (US)

• Routine ophthalmic review up to 7yr of age

• Poor prognosis with delayed diagnosis

• Trilateral retinoblastoma fatal

• Risk for secondary malignancy in children with germline RB1 mutations (osteosarcoma, soft
tissue sarcomas and malignant melanoma).

• Some tumors can regress spontaneously and When untreated can be fatal
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 Prognosis
Spread
• Can spread to optic nerve and subarachnoid space

• Or even to the brain,skull, distal bones and lymph nodes

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 Reference
• Robert M. Kliegman, MD, Joseph W. St Geme Iii, MD, Nathan J. Blum, MD,
Robert C. Tasker, MBBS, MD, Samir S. Shah, MD, MSCE, Karen M. Wilson,
MD, MPH.(2020).Nelson Textbook Of Pediatrics. Elsevier Publishers.
• Krishna M Goel,MD,DCH,FRCP,Devender K Gupta,MS,Mch,
(2012),Hutchison's pediatrics textbook second edition ,japee brothers
publishers.
• https://youtube/r500jd4r8Rs?si=Og4cL49D-PGzcbQ8

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