04/14/2023 1

By Abril SantosUniversidad Popular Autónoma del Estado de Puebla

International Observership Program

Retinoblastoma

04/14/2023 2

Most frequent malignant intraocular tumor during childhood. 1/15,000 – 1/20,000 • Greater amount due to better treatments.• Age of diagnosis depends on socio-economic conditions.

Introduction

04/14/2023 3

Age of Diagnosis* Type of Retinoblastoma

12 months Bilateral (20-30%)

24 months Unilateral

18 months Total average

Unilateral Bilateral*Average

04/14/2023 4

Genetic Characteristics

Presentation of Retinoblastoma• Sporadic (94%)• Family History (6%)

• Due to an spontaneous mutation• 80% of the cases is somatic• The other 20% is germinal - heritage

04/14/2023 5

Knudson’s TheoryFor a retinoblastoma to exist 2 mutations are required to happen.

Hereditary1°- Germinal

(In all the cells)2°- Somatic mutation

NON Hereditary1° y 2°- Somatic

2 mutations must occurConsecutively in the same ȼ

04/14/2023 6

04/14/2023 7

NON HereditarySomatic + somatic mutation : Single

tumor. Unilateral.Late start (2 years)

HereditaryGerminal + somatic mutation : Bilateral,

multifocal tumor.Early start (1 year)

Unifocal Multifocal

04/14/2023 8

Retinoma* Associated Lesions

*Retinoma is a benign variant, initially considered a tumor regression, but recent evidences suggest that it rather represents a pre-malignant lesion.

1. Spontaneous Regression of Retinoblastoma2. Spontaneous Growth arrest of Retinocytoma or Retinoma

Phthisis Bulbi Retinal Scars

04/14/2023 9

Hereditary

RetinoblastomaMore likely to present another kind of tumor.• Osteosarcoma• Pinealoblastoma (Trilateral

retinoblastoma)

04/14/2023 10

Development of the eye from the neural tube. Optic vesicles and the inverted optic cup are forming the retina.

04/14/2023 11

The RB1 has a longitude of 180,388 pairs of bases and 27 exons.

The RB1 gen is localized within the 13th chromosome in the q14.2 region.

Retinoblastoma

GEN

04/14/2023 12

pRb Functions*

Whatever type of mutations results in increased RB phosphorylation and inactivation of RB function.

*Inhibits the progression of the cellular cycle before the mitosis

04/14/2023 13

PRb1 y P53

• Rb1 y P53 are in charge of stopping damaged cells into the cellular cycle. • So, if these are damaged, there will be a filtration of abnormal cells.

04/14/2023 14

Clinical Features• Asymptomatic – Early stage.• Leukocoria (66% - 1st sign)• Strabismus (20%)• Hyphema• Rubeosis iridis• Mydriasis• Areflexic pupils• Secondary Glaucoma• Hypopyon

04/14/2023 15

CLINICALFINDINGS

1st2nd

04/14/2023 16

Diagnosis

• Fundus examination

• Eye ultrasound

• Head CT

• MRI

• Fluorescein Angiography

04/14/2023 17

Types of Retinoblastoma

Exophytic Endophytic

04/14/2023 18

Endophytic.- Invading vitreous, retinal vascular tortuosity and dilation.Variant: Diffuse infiltrative *Simulates endophthalmitis with hypopyon*Exophytic.- Invades subretininan space, vasculature goes over the tumor.• Variant: Flat retinoblastoma

04/14/2023 19

1-Initial stage 2

3 4-Advanced

04/14/2023 20

Extra Ocular Invasion

Orbit and optic nerve are invaded in very advanced cases,

specially when there is secondary glaucoma.

04/14/2023 21

Treatment• Optic nerve ablation to prevent invasion. • Ocular enucleation• Chemotherapy and Radiotherapy

04/14/2023 22

After Treatment

• Ocular Implants• Ocular Prosthesis

04/14/2023 23

Types of Implants

1. Mesh-wrapped Bioceramic

2. Bioceramic

3. Egg-shaped Bioceramic

4. Silicone

04/14/2023 24

Types of Prosthesis

1. Plastic Acrylic2. Cryolite glass (only a few)

04/14/2023 25

Differential Diagnosis

Osteosarcoma Cataract Pseudo-retinoblastoma

04/14/2023 26

Causes for Pseudo-retinoblastoma

Coat’s Disease Persistent Fetal Vasculature

Vitreous Hemorrhage

Ocular Toxocariasis

04/14/2023 27Comparison of two cases of a Retinoblastoma

04/14/2023 28

References1. Shields C, Schoenberg E, Kocher K, Shukla S, Kaliki S, Shields J. Lesions Simulating Retinoblastoma (Pseudoretinoblastoma) in 604 Cases. Ophthalmology. 2013;120(2):311-316.2. Gil-Gibernau J, Galan Terraza A. Retinoblastoma y otras causas de leucocoria en el nino. [S.l.: s.n.]; 1984.3. Turaka K, Shields C, Bianciotto C, Shields J. Pinealoblastoma and Pineal Cysts among Patients with Intraocular Retinoblastoma Treated with Chemotherapy. International Journal of Radiation Oncology*Biology*Physics. 2011;81(2):S297-S298.4. Shields J, Shields C, Shields J. Eyelid, conjunctival, and orbital tumors. Philadelphia: Lippincott Williams & Wilkins; 2008.5. Rodriguez-Galindo C, Wilson M. Retinoblastoma. New York: Springer; 2010.6. Knudsen et al, University of Cincinnati, in a study of 2000 stated that pRB is not only involved in the regulation of the G1/S Checkpoint but it is also required for an intra-S-phase response to DNA damage.