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
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.
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.
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
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)
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
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
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)
53.
54.
55.
56. T1 C+ (Gd)
The mass usually enhances relatively homogeneously
when small
Larger tumours often have areas of necrosis,
rendering it heterogeneous
57.
58.
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
61.
62. Careful assessment of the optic disc and optic nerve
should be carried out to assess for involvement
63.
64. Extra-ocular extension through the sclera will be
visible as interruption of the otherwise hypointense
non-enhancing sclera by enhancing tumour
67. COMPLICATIONS
(1) Metastases to: meninges (via
space), bone marrow, lung,
subarachnoid
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%
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 enzymelinked 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.
retinal detachment
separation of the inner layers of the retina from the pigment epithelium, which remains attached to the choroid. Retinal detachment occurs most often as a result of degenerative changes in the peripheral retina and vitreous body, which produce holes or tears in the retina that can range from minute breaks no larger than 0.1 mm to extensive holes that extend over the entire fundus. Causes include trauma to the eyeball, severe contusions, inflammatory lesions and sometimes ocular surgery.
rhegmatogenous detachment
retinal detachment with holes.
nonrhegmatogenous detachment
retinal detachment with no holes present.
Transverse B-scan showing a large, endophytic, irregularly shaped lesion (green arrow) involving most of the posterior fundus with associated retinal detachment (red arrow). There are multiple, focal calcified areas (blue arrow), causing shadowing of the orbit.
Ultrasonographic (US) image obtained with a high-frequency linear transducer shows the heterogeneous, nodular mass (arrow) in the globe apposed to the retina and posterior to the lens (arrowhead). (f) US image shows posterior acoustic shadowing (arrow).
Figure 7d. Retinoblastoma in a 7-year-old girl who complained of blurry vision in her right eye. (a) Photomicrograph (original magnification, ×400; H-E stain) shows Flexner-Wintersteiner rosettes with central lumina (straight arrows). Numerous mitotic figures are noted (arrowheads) as well as areas of necrosis (*). Also note the central focus of proliferative vessels with plump endothelial cells (curved arrow). (b) Photomicrograph (original magnification, ×20; H-E stain) shows a homogeneous mass of tumor cells in the posterior globe (*) that invade the optic nerve (arrows). (c) Photomicrograph (original magnification, ×100; H-E stain) shows basophilic neoplastic cells in the optic disc (*) crossing the lamina cribrosa (arrows) into the optic nerve (arrowheads). (d) Photograph of the sectioned gross specimen shows an irregular whitish mass (*) arising from the thickened retina (arrowhead). (e) Ultrasonographic (US) image obtained with a high-frequency linear transducer shows the heterogeneous, nodular mass (arrow) in the globe apposed to the retina and posterior to the lens (arrowhead). (f) US image shows posterior acoustic shadowing (arrow).
CT is the preferred method to image the
child with leukokoria because it is sensitive to calcification
in retinoblastoma. CT demonstrates clumped or punctate calcification
(in 95 per cent of cases) in the posterior part of
the globe extending into the vitreous, with minimal enhancement.
In advanced cases the tumour may fill the globe (Fig.
61.1). If CT shows calcification in an intra-ocular mass in a
child less than 3 years of age, it should be considered a retinoblastoma
until proven otherwise. Absence of calcification
means this diagnosis is unlikely, since it is rare in other causes
of leukokoria.
Huge retinoblastoma with orbital and intracranial
involvement. Axial CT image with contrast medium. The right globe is
filled by a calcified mass. The optic nerve is also calcified and surrounded
by a soft tissue mass that replaces orbital fat and extends through the
optic foramen. There is involvement of the suprasellar cistern, temporal
lobe, greater wing of sphenoid and temporal fossa.
Figure 8a. Trilateral retinoblastoma in a child of unknown age. (a) Axial CT image enhanced with intravenous contrast material shows bilateral hyperattenuating nodular masses containing dense foci of calcification (arrowheads). (b) Axial CT image enhanced with intravenous contrast material shows a large, round, intensely enhancing mass in the pineal region, which causes hydrocephalus.
Coronal T1 weighted image shows a
mass in the lower part of the left globe with relative high signal intensity. Note the smaller RB in the upper part of the right
globe
Axial high-resolution three-dimensional T2 weighted image shows low signal intensity left
intraocular mass with a few signal void regions that correspond to areas of calcification
Multifocal retinoblastoma (RB). Axial threedimensional
T2 weighted image of the globe at 3 T shows
multifocal RBs (arrows) seen in the left globe.
Endophytic retinoblastoma. Contrast T1 weighted
image shows intense contrast enhancement of the right
intraocular mass.
Diffuse retinoblastoma. Contrast T1 weighted
image at 3 T with surface coil shows diffuse infiltrative
placode lesion with retinal detachment (arrow).
Anterior segment eye enhancement. Axial contrast
T1 weighted image shows enhancement (arrows) of
anterior segment in a patient with retinoblastoma (RB),
which may be due to extension of RB or a tumour-induced
angiogenesis in the iris.
Retinoblastoma (RB) with optic nerve invasion. (a) Axial contrast T1 weighted image shows right RB with infiltration
of a small part of the right optic nerve (arrowhead). (b) Axial contrast T1 weighted image in another patient shows left ocular
mass infiltrating most of the left optic nerve (arrow).
