Retinoblastoma

1. Case presentation
Dr Tariq Masood
TMO Radiology Department,
HMC

3. Case
2 year old male child
Mother had noticed some white spot in the window
of his left eye since early childhood
And gradual protrusion of the eye

5. Clinical differentials?

6. Leucocoria
•TUMOR
–Retinoblastoma (most common cause--58%)
–Retinal astrocytic hamartoma (3%):
–Medulloepithelioma (rare)
•DEVELOPMENTAL
–Persistent hyperplastic primary vitreous
•(2nd most common cause--28%)
–Coats disease (16%)
–Retrolental fibroplasia (3--5%)
–Coloboma of choroid / optic disc

7. •INFECTION
–Uveitis
–Larval granulomatosis (16%)
•DEGENERATIVE
–Posterior cataract
•TRAUMA
–Retinopathy of prematurity (5%)
–Organized vitreous hemorrhage
–Long-standing retinal detachment

8. •Leukocoria in Normal-sized Eye
•CALCIFIED MASS
–Retinoblastoma
–Retinal astrocytoma
•NONCALCIFIED MASS
–Toxocaral endophthalmitis
–Coats disease
•Leukocoria with Microphthalmia
•UNILATERAL
–Persistent hyperplastic primary vitreous (PHPV)
•BILATERAL
–Retinopathy of prematurity
–Bilateral PHPV

11. Diagnosis?

12. RETINOBLASTOMA

13. History/Overview
• In 1597 it starts with a man named Pieter Pauw and
his autopsy findings of cancerous tumor originating in
a 3 year-old eye. The results of the autopsy were
later found by Edwin B. Dunphy who suggested
Retinoblastoma.

14. In 1872 a Brazilian ophthalmologist called Hilário
de Gouvêa treated a boy with retinoblastoma.
Later in life, the boy had two daughters that also
had retinoblastoma. This proposed perhaps the
disease was genetic.

15. In 1986 Dr. Knudson discovered the retinoblastoma
gene and then a year later he isolated the gene
making it the first ever tumor suppressor to be
identified.

16. In one of Knudson’s cases he found that one family
had a genetic past of the disease and found that the
gene causing the disorder is located in chromosome 13
that has been mutated.

17. Retinoblastoma
Rare malignant congenital intraocular tumor arising
from primitive photoreceptor cells of retina (included
in primitive neuroectodermal tumor group)
AKA neuroepithelioma of the retina

18. Cause of Retinoblastoma
1. Mutations
Mutations in the RB1 gene are responsible for most
cases of retinoblastoma. RB1 is a tumor suppressor
gene, which means that it normally regulates cell
growth and keeps cells from dividing too rapidly or in
an uncontrolled way.

19. 2.Chromosomal anomaly–
A small percentage of retinoblastomas are caused by
deletions in the region of chromosome 13 that
contains the RB1 gene. Because these chromosomal
changes involve several genes in addition to RB1,
affected children usually also have;
microcephaly, ear changes, facial dysmorphism,
mental retardation, finger + toe abnormalities,
malformation of genitalia.

20. TYPES
A.Non-Heritable form
B.Heritable form

21. A.Non-Heritable form(60%)
RB1 mutations occur only in the eye and cannot be
passed to the next generation.
typically only one eye is affected and there is no
family history of the disease.
Affected individuals are born with two normal copies
of the RB1 gene.
Then, usually in early childhood, both copies of the
RB1 gene in retinal cells acquire mutations or are lost
Mean age at presentation--23 months

22. B.Heritable form(40%)
RB1 mutations occur in all of the body's cells, including
reproductive cells (sperm or eggs).
People with germinal retinoblastoma may have a family
history of the disease, and they are at risk of passing on
the mutated RB1 gene to the next generation.
Mutations in the RB1 gene appear to be inherited in an
autosomal dominant pattern.

23. Autosomal dominant inheritance suggests that one
copy of the altered gene in each cell is sufficient to
increase cancer risk.
A person with germinal retinoblastoma may inherit
an altered copy of the gene from one parent, or the
altered gene may be the result of a new mutation that
occurs in an egg or sperm cell or just after
fertilization.

24. For retinoblastoma to develop, a mutation involving
the other copy of the RB1 gene must occur in retinal
cells during the person's lifetime.
This second mutation usually occurs in childhood,
typically leading to the development of
retinoblastoma in both eyes.

25. B.Heritable form
1.Heritable sporadic form
2.Familial retinoblastoma

26. 1.Heritable sporadic form (20-25%)-- sporadic germinal
mutation (50% chance to occur in subsequent
generations)
Mean age at presentation:
12 months--bilateral retinoblastomas in 66%

27. 2.Familial retinoblastoma (5-10%)
autosomal dominant with abnormality in
chromosome 13
Mean age at presentation: 8 months
usually 3 to 5 ocular tumors per eye
bilateral tumors in 66%
Risk of secondary nonocular malignancy:
Osteo, chondro, fibrosarcoma, malignant
fibrous histiocytoma

28. Trilateral retinoblastoma (rare variant)
 bilateral retinoblastomas +
neuroectodermal pineal tumor
(pineoblastoma)
Quadrilateral retinoblastoma
 trilateral retinoblastoma + 4th focus in
suprasellar cistern

29. Incidence
1:15,000 to 30,000 livebirths
 Most common intraocular neoplasm
in childhood
 1% of all pediatric malignancies

30. Mean age at presentation is 18 months
98% in children <5 years of age
M:F = 1:1

31. Patterns of growth
Endophytic
Growth occurs inwards into the vitreous ± anterior
chamber
Cell clusters may detach and float in the vitreous
(vitreous seeding)

32. Exophytic
Growth occurs outwards
Proliferation into subretinal space with non-
rhegmatogeneous retinal detachment + invasion of
vascular choroid (hematogenous spread)

33. Combined
Endophytic and Exophytic

34. Location
Posterolateral wall of globe (most commonly)
60% unilateral 40% bilateral + frequently
synchronous (90% bilateral in inherited forms)
Normal ocular size/Enlarged

35. • Leukocoria - 60%• Strabismus - 20%• Secondary glaucoma
• Anterior segment invasion• Orbital inflammation • Orbital invasion
Presentations of retinoblastoma

36. PROPTOSIS

37. Imaging of RB
Ultrasound
CT scan
MRI

38. Imaging is crucial for timely management and
survival of patients with retinoblastoma.
 Cross-sectional imaging are done to exclude ;
Other retrobulbar tumours with globe invasion,
Optic nerve invasion by the retinoblastoma
Intracranial metastases

39. US
Heterogeneous hyperechoic solid intraocular mass
Cystic appearance upon tumor necrosis
Secondary retinal detachment in all cases
Acoustic shadowing (in 75%)
Vitreous hemorrhage frequent

41. Figure 7e. Retinoblastoma in a 7-year-old girl who complained of blurry vision in her right
eye.

42. Figure 7d. Retinoblastoma in a 7-year-old girl who complained of blurry vision in her right
eye.
Chung E M et al. Radiographics 2007;27:1159-1186

43. CT Scan
CT is sensitive to calcification.
 Clumped or punctate calcification (in 95 per cent of
cases) in the posterior part of the globe extending into
the vitreous
Minimal enhancement.

44. CT Scan
•Calcification in an intra-ocular mass in a child (3 yrs,
retinoblastoma until proven otherwise. Absence of
calcification means this diagnosis is unlikely, since it
is rare in other causes of leukocoria.
•Retinoblastoma is the most common cause of orbital
calcifications!

45. CT Scan
Solid smoothly marginated lobulated retrolental
hyperdense mass in endophytic type
 Exophytic type grows subretinally causing retinal
detachment
Partial punctate / nodular calcification

46. Dense vitreous (common)
Extraocular extension (in 25%): optic nerve
enlargement, abnormal soft tissue in orbit,
intracranial extension
± Macrophthalmia

48. CT diagnosis of retinoblastoma
Calcification

51. Figure 8a. Trilateral retinoblastoma in a child of unknown age.

52. MRI
MRI is the modality of choice for pre-treatment
staging on retinoblastoma
T1 : Intermediate signal intensity, hyperintense c.f.
vitreous
T2 : Hypointense c.f. vitreous
subretinal exudate usually hyperintense on
T1WI + T2WI (proteinaceous fluid)

56. T1 C+ (Gd)
The mass usually enhances relatively homogeneously
when small
Larger tumours often have areas of necrosis,
rendering it heterogeneous

59. Linear enhancement of the choroid beyond the
margins of the tumour should raise the possibility of
choroidal involvement, although inflammation may
lead to similar appearance

60. Enhancement of the anterior chamber need not
represent tumour involvement, with hyperaemia,
uveitis and iris neovascularisation all leading to
asymmetric enhancement

62. Careful assessment of the optic disc and optic nerve
should be carried out to assess for involvement

64. Extra-ocular extension through the sclera will be
visible as interruption of the otherwise hypointense
non-enhancing sclera by enhancing tumour

65. PROGNOSIS
Spontaneous regression in 1%;

66. Poor prognostic signs
Contrast enhancement
Optic nerve
involvement
Choroidal invasion
Large tumor
Anterior locations
Poor cellular
differentiation
Older children

67. COMPLICATIONS
 (1) Metastases to: meninges (via subarachnoid
space), bone marrow, lung, liver, lymph nodes
(2) Radiation-induced sarcomas develop in
15-20%

68. Mortality
Choroidal invasion:
65% if significant, 24% if slight
Optic nerve invasion:
<10% if not invaded
15% if through lamina cribrosa
44% if significantly posterior to lamina cribrosa
Margin of resection not free of tumor: >65%

69. Differential diagnosis
Retinal Astrocytic hamartoma
Retrolental fibroplasia
Coat’s disease
Peristent hypertrophic primary vitreous
Toxocaral infestation
Norrie’s disease

70. DDx
Retinal astrocytic hamartoma.
May occur in association with TS or NF or an isolated
abnormality.
May be bilateral multiple small retinal masses.
 calcification may occur in the older child

71. •Coats disease
•Coats’ disease is a primary congenital, non-familial
idiopathic vascular anomaly of the retina. It is
characterised by telangiectatic, leaky retinal vessels that
lead to progressive retinal exudates. It usually occurs
in young males (70%) with an incidence peak at age 6–8
years. It is mostly unilateral (90%). Patients present with
leukocoria, strabismus or painful
glaucoma..

72. Calcification is rare,allowing differentiation from RB.
CT shows homogeneous increased density within the
vitreous chamber,retinal detachment and lack of
enhancement after contrast administration.
The MRI findings are retinal detachment
without intraocular mass and high signal subretinal
effusion on both T1W and T2W MRI

73. Retrolental fibroplasia
Retinopathy of prematurity causes retro-lental
fibroplasia with the development of retrolental
membranes.
Present usually with bilateral leucocorea at the age of
7-10weeks with a history of prematurity and oxygen
therapy.
No Calcification.
Microphthalmia.

74. Persistent hyperplastic primary vitreous
is caused by the failure of the embryonic hyaloid
vascular system to regress normally and extensive
proliferation of embryonic connective tissue It is
characterised by a leukocoria in a microphthalmic
eye.
Small irregular lens with shallow anterior chamber.
If bilateral,PHPV may be part of the diagnosis of
Norrie’s disease.

75. On CT
No calcification.
Increased attenuation of vitreous with enhancement
of abnormal intravitreal tissue.
Triangular retrolental density with its apex on the
posterior lens and base on the posterior globe.

76. Toxocara canis infection
Sclerosing endophthalmitis is a granulomatous
chorioretinitis uveitis that develops secondary to a
Toxocara canis infestation, in more than 5 yrs age
Present with leucocorea----often bilateral.
It differs from RB by its central position, the fact that
it is hyperintense to vitreous on T2 weighted images,
the patient age and a positive serologic enzyme-
linked immunosorbent assay (ELISA).

77. CT demonstrate a hyperdense vitreous
cavity,sometimes with retinal detachment.No
enhancement is seen.

78. Norrie disease
Rare X-linked recessive syndrome consisting of
retinal malformation, deafness and mental
retardation. Female carriers are completely healthy.
The ocular changes in male patients include retinal
detachments and vitreo-retinal haemorrhage

79. Treatment
•Depends on tumour size and the stage of disease and
involves one or more modalities:
•Conservative external-beam radiation therapy
cryotherapy
laser photocoagulation
radioactive plaque therapy
thermochemotherapy
tumour reduction chemotherapy
•Surgical enucleation
en bloc resection

80. Treatment
Advantages Disadvantages
Photocoagulation (Laser Therapy) The laser beam focuses on the
cancerous tumor, cuts off blood
supply to the tumor and shrinks it.
Depending on the size of the tumor,
chemotherapy may be needed for
larger tumors that cannot be shrunk
by just laser.
Cryotherapy (Freezing Treatment) The tumor is frozen and thawed a
several times by a cold gas and it
deflates the tumor with no signs of a
tumor at all.
The tumor will leave a pigmented
scar and the eye lid will swell for a
couple of days.
Chemotherapy After the extensive cycles of chemo,
the cancer cells are reduced,
therefore, shrinking of the tumor.
There are several cycles, and there is
a port necessary to draw blood, and
insert the drugs.
Enucleation This is removal of the eyeball and the
tumor is extracted when no other
option is possible due to the size of
the tumor.
The whole eyeball is removed and it
causes permanent eye damage
because there is no way of an eye
transplant.

81. WE HATE RETINOBLASTOMA

82. THANKS