Cancer in children

RETINOBLASTOMA

Introduction

Retinoblastoma is malignant endo-oculer

tumor of children arising in the embryonic
neural retina.
Prototype model for hereditary cancer
development .
Frequently 1 in 15.000 18.000 live birth in
developed country.
No predisposition for sex and race.
Average age of patients at diagnosis is 24
months in unilateral and 13 months in
bilateral cases.

Genetic

Retinoblastoma can occur in a familial or sporadic form.

Only 6-10% familial, classified in two group: unilateral
or bilateral and heritable or non heritable.
Non heritable cases are always unilateral, whereas 90%
of the heritable
cases are bilateral and 10% are
unilateral. All bilateral cases are heritable
Knudson (1971) : mathematical model to explain the
hereditary of retinoblastoma is two hits must occur at
a gene level for retinoblastoma.
The retinoblastoma gene (RB1) was isolated at
chromosome 13q 14 and cloned in 1987. Abnormality at
chromosome 13q14 can be detected by conventional
karyotyping studies in only 5% of the cases
Molecular diagnosis of retinoblastoma plays a mayor
rule in genetic counseling.

Pathology

Retinoblastoma is a tumor neuroepithelial origin

which may be classified as one of the primitive
neuroectodemral tumor in childhood.
Classically, two types : highly undifferentiated
retinoblast (most common) and differentiated
photoreceptor cell with neuroepithelial rossette
formation (Flexner-Wintersteiner rossette)
Retinoblastoma can disseminate outside the eye,
following the optic nerve and/or subarachnoid
space to chiasm, the brain and the meninges.
Haematogenous metastases involves CNS, facial
structures, and bones of the skull. Bone and bone
marrow ,liver, lung and any other organ (less)

Sign and symptoms

Sign of retinoblastoma are often first notes by parent:

leukocoria ; stabismus, red, painful eye frequently
accompanied by glaucoma and poor of vision.
Less common sign: rubeosis iridis; orbitas cellulitis;
heterochromia iridis; uni lateral mydriasis; hypemia;
nystagmus and failure to thrive and abnormal facies
A syndrome associated with deleetion of the long arm of
chromosome 13 ( the 13q- deletion syndrome) :
microcephaly;hypertelorism;
microopthalmos
;epicanthal fold; micrognathia ; short neck with lateral
fold, low set ears, imperforate anus, hypoplastic or
absent thumbs and mental retardation.

Diagnosis

The important step in diagnosis is: under

anaesthesia fully dilated pupils; with indirect
opthalmoscopy and scleral depression by an
opthalmologist.
Diagnostic can accurately without histo
patological confirmation.
USG : very helpful in the differential diagnosis
of children with leukocoria.
CT and MRI: for evaluated the optic nerve;
orbital; CNS involvement and intraocular
calcification.
Bone marrow aspiration and lumbar puncture
for cytologic examination (LCS)

Differential diagnosis of retinoblastoma

Intraocular reetinoblastoma:

Coats disease

Retrolental fibroplasia

Endopthalmitis

Toxocara infection

Meduloepitheloma

Cataracts

Uveitis

Peersisten hiperplastic
primary vitreous

Astrocytic hamartomas

Extraocular retinoblastoma:
Orbital cellulitis
Metastases neuroblastoma
Orbital rhabdomyosarcoma
Leukemia
Lymphoma

Reese - Ellsworth Staging system for intraoculer

retinoblastoma
Grroup
I

Description
(a)
(b)

Solitary tumor less than 4 dd (disc diameter) at or

behind the equator
Multiple tumor non large than 4 dd, all at or behind
the equator

II

(a)
(b)

Solitary tumor 4-10 dd,at or behind the equator

Multiple tumor, 4-10 dd at or behind the equator

III

(a)
(b)

Any lesion anterior to the equator

Solitary tumor laarge than 10 dd behind the equator

IV

(a)
(b)

Multiple tumor, some large than 10 dd

Any lesion extending anterior to the ora serrata

(a)
(b)

Massive tumor involving over half the retina

Vitreous seeding

Treatment
Aspect of treatment:
Local therapeutic :
to treat intra ocular disease
Systemic therapy :
for extra ocular ,regional
and matastases
In developed country:most present intra ocular,
survival 95%.
Size, number and location of tumor are taken to
choose the best therapy.
Bilateral retinoblastoma come with advanced intra
ocular disease in one eye.
In developing country retinoblastoma is diagnosis
after extra ocular spread. Aim of treatment to save
patients life, since death from metastatic is possible

Treatment (contd)

Surgery:
Enucleation is the simplest and safest therapy
* Under 2 years : facial asymmetry
* Group V : require enucleation
* Enucleation mandatory when present:
glaucoma; anterior chamber invasion or
rubeosis iridis
local therapy cannot be evaluated due to a
cataract or failure to follow a patient closely
* Vitrectomy is contraindicated

External beam radiotherapy

Retinoblastoma is a radiosensitive and radio

therapy is the elective local therapy for
retinoblastoma. Long term side effect limit its use.
EBRT is usually delivered using a linier
accelerator to dose of 40-45 Gy involving whole
retina .
Most recurrences after radiotherapy can be treated
with cryo or photocoagulation.
Long term sequelae of radiotherapy is: growth
inhibition of orbital bone; cosmetic and increase
of secondary malignancy.

Plaque radiotherapy
Radioactive episcleral plaque using
60Co; 106 Ru; or 125 I.
Usually for : small and medium
sized single tumors not amenable
to cryo or photocoagulation
Recently as primary therapy after
chemoreduction.

Cryo and photocoagultion

Use to treat small (usually less
than 5 mm) and accessible tumors.
Widely
available and can be
repeated several times until local
control is achieved
Cryotherapy : to treat anterior tumors
Photocoagulation : to treat posterior tumor

Newer modality
Chemotherapy for intra ocular disease in
order to decrease tumor size and make the
tumors suitable for local therapy
In past: chemotherapy ineffective for
intraocular disease
Recently : with the newer drug with greater
penetration of the eye, this modality has
reemerged

Chemotherapy
The agents used commonly is:

Carboplatin

Cisplatin

Etoposide

Cyclophosphamide

Vincristine

Adriamycine
The role of intrathecal chemotherapy and cranial
radiotherapy to prevent of CNS dissemination
is not established.