Retinoblastoma is a rare form of eye cancer that develops from immature retinal cells in children younger than 5 years old. It is caused by mutations in both copies of the RB1 tumor suppressor gene. Symptoms may include a white pupil, crossed eyes, eye inflammation or pain, and vision loss. Diagnosis involves eye examination and imaging tests. Treatment depends on tumor size and spread but may include focal therapies like laser treatment or chemotherapy followed by focal therapies. Outcomes are generally good if caught early, but survivors require long-term monitoring due to risks of secondary cancers from radiation treatment.

1. RETINOBLASTOMA
AMANYIRE DICKSON
REG NO. : BMS/7925/163/DU
MBChB V - KIU – WC
JRRH
OCTOBER 14, 2022
SUPERVISOR
DR. WALUFU EGESA IVAN

2. OUTLINE
1. GENERAL ASPECTS
2. EPIDEMIOLOGY
3. RISK FACTORS
4. CLASSIFICATION
5. PATHOGENESIS
6. PATHOLOGY
7. CLINICAL FEATURES
8. DIAGNOSIS
9. MANAGEMENT
10.PROGNOSIS.
Figure 1: retinoblastoma with orbital extension5

3. GENERAL ASPECTS AND EPIDEMIOLOGY
Retinoblastoma is the most common primary, malignant intraocular
tumour of childhood yet rare form of cancer that rapidly develops from
the immature cells of a retina accounting for 4% of all pediatric
malignancies3
66–75% have unilateral tumors, with the remainder having bilateral
retinoblastoma and >90% of cases are diagnosed in children <5 yr old. 3
Risk of retinoblastoma may be increased in children conceived by in
vitro fertilization and old age in fathers.2,3

4. A retinoblastoma forms when both copies of
the RB1 gene located on chromosome are
affected by a gene mutation2,3,4,5
 Cancer development is believed to
follow the “two-hit” hypothesis first
described by the Dr. Alfred Knudsen.2
CLASSIFICATION & PATHOGENESIS
Fig 2: Classification of retinoblastoma2,3
Fig 3: Pathogenesis of Retinoblastoma6

5. 6. PATHOLOGY
 Histologically, retinoblastoma
appears as a small round blue cell
tumor with rosette formation
(Flexner-Wintersteiner rosettes).3,6
Tumors can be3,4,5,:
Endophytic tumors
Exophytic tumors
Diffuse infiltrating tumors
Fig 4: A large white tumor mass noted
within the posterior chamber of the
enucleated eye2
Fig 5: A: illluistration of A halo of cells
surrounding a largely empty central hub. Small
cytoplasmic extensions from the cells project into
the lumen.6 B. Histologic appearance6
A B

6. CLINICAL FEATURES2,3,4,5
 Leukocoria
 Strabismus
 Glaucoma
 Red, inflamed eye(s)
 Nystagmus
 Decreased vision
 Anisocoria
 Signs and symptoms of metastatic disease
Fig 6: Leukocoria6
Fig 7: Strabismus6

7. DIAGNOSIS 2,3,4,5,7
Complete history taking and full
physical examination.
 Family history of retinoblastoma
 Red reflex:
 Corneal light reflex / Hirschberg test
 Eye examination: checking for any
structural abnormalities
 Indirect ophthalmoscopy with scleral
indentation or slit-lamp evaluation can
detect retinoblastoma tumors.
Other tests include:
 Ultrasonography: Detects calcification
and the tumour dimensions.
 CT Scan:
 Detects calcification, involvement of
the optic nerve, orbit or CNS
 MRI:
 evaluation of the optic nerve and of
the detection of pinealoblastoma
 Smart-phone app that can detect
leukocoria in photos
 Cerebrospinal fluid and bone marrow
evaluation for tumor metastasis and
radionuclide bone scan are required
only if indicated by other clinical,
laboratory, or imaging findings.

8. DIAGNOSIS (Contd……) 2,3,4,5,7
DIFFERENTIAL DIAGNOSIS FEATURES
Persistent hyperplastic primary vitreous
(PHPV):
 Leukocoria, Cataract, Nystagmus,
Blurred vision, blindness, strabismus,
Coats disease:  Retinal detachment, Leukocoria
Toxocara canis:  Endophthalmitis, Ocular granulomas,
Retinal detachment
Retinopathy of prematurity (ROP):  Retinal detachment.
Familial exudative vitreoretinopathy (FEVR)  Retinal folds, retinal tears, retinal
detachments.
Cataract  Leukocoria

9. MANAGEMENT
Treatment2,3,4,5 Late Effects of Retinoblastoma Therapy2
Focal therapy:
Laser photocoagulation,
Transpupillary Thermo Therapy (TTT),
Cryotherapy,
Plaque brachytherapy.
The risk of second malignancies is further
increased by the use of radiation and cancer
chemotherapy.
Other radiation-related late adverse effects
include;
 Cataracts,
 Orbital growth deformities,
 Lacrimal dysfunction,
 Late retinal vascular injury
Local therapy:
External beam radiotherapy (EBRT).
Chemotherapy:
Followed by focal treatment is the primary
treatment of choice for intraocular retinoblastoma.
Enucleation:
 Indicated for advanced intraocular retinoblastoma,
especially in unilateral cases. Curative in 90%
Investigational Therapies.8
 Suicide gene therapy.
 Systemic chemotherapy with autologous
hematopoietic stem cell rescue for children with
severe forms of retinoblastoma.
Genetic counselling & Follow-up
Psychosocial support is essential for the entire
family.

10. PROGNOSIS
 Retinoblastoma that has spread outside of the eye is of poor prognosis.
 Trilateral retinoblastoma, disease involving both eyes and the pineal
region, is almost universally fatal. 2
 Children with germline RB1 mutations are at significant risk for
development of second primary malignancies, especially osteosarcoma
and also soft tissue sarcomas and malignant melanoma. 2,3
 The risk of second malignancies is further increased by the use of
radiation and cancer chemotherapy,2,3

11. REFERENCES
1. Khedekar, A., Devarajan, B., Ramasamy, K., Muthukkaruppan, V., & Kim, U. (2019). Smartphone-based
application improves the detection of retinoblastoma. Eye, 33, 1. https://doi.org/10.1038/s41433-
018-0333-7
2. Retinoblastoma Causes, Risk Factors, and Prevention. (2018). AMERICAN CANCER SOCIETY. Retrieved
7/10/2022 from https://www.cancer.org/cancer/retinoblastoma/causes-risks-prevention/risk-
factors.html
3. Kliegman, R. M., St, J. W., Blum, N. J., & Bennett, W. H. (2017). RETINOBLASTOMA. In R. E. Behrman
(Ed.), Nelson’s Textbook of Pediatrics (20 ed., pp. 2476-2477). Springer.
4. Pizzo, P. A., & Poplack, D. G. (2015). RETINOBLASTOMA. In Principles and Practice of Pediatric
Oncology (7 ed., Chapter 27). Lippincott Williams & Wilkins.
5. Goel, K. M., & Gupta, D. K. (2012). RETINOBLASTOMA. In Hutchison's Paediatrics (2 ed., pp. 591-593).
JP Medical Ltd.
6. Ellison, D., Love, S., Chimelli, L. M. C., Harding, B., Lowe, J. S., Vinters, H. V., . . . Yong, W. H. (2012).
Neoplasms of the pineal gland. In Neuropathology: a reference text of CNS pathology (3 ed.). Elsevier
Health Sciences.
7. Eye of the Storm: the impact of ‘not knowing’ on mental health. (2021). WORLD EYE CARE HOPE.
Retrieved OCT 9, 2022 from https://wechope.org/awareness/eye-of-the-storm-retinoblastoma-
awareness-mental-health/

12. REFERENCES (Contd….)
8. Rodriguez-Galindo, C., Chantada, G., Haik, B., & Wilson, M. (2007). Retinoblastoma: Current treatment
and future perspectives. Current treatment options in neurology, 9, 294-307. doi:10.1007/s11940-007-
0015-4