Download MBBS Orthopaedics PPT 15 Retinoblastoma Lecture Notes

Retinoblastoma

Epidemiology
The most common primary intraocular malignancy of

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childhood

3% of all childhood cancers
The second most common malignant intraocular tumour

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1 in 18,000 live births
25-30% cases are bilateral but asymmetric
Survival rates are over 95% in specialized centers but are

much lower in the developing world.

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Genetics & Histopathology
RB1 is the tumour suppressor gene in which

mutations/deletion predisposes to retinoblastoma.

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Tumours are composed of small basophilic cells (retinoblasts)

with large hyperchromatic nuclei and scanty cytoplasm.

Characterized by the formation of structures known as

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rosettes

Flexner?Wintersteiner,
Homer?Wright and fleurettes

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Growth may be endophytic (into the vitreous) with seeding

of tumour cells throughout the eye, or

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Exophytic (into the subretinal space) leading to retinal

detachment, or mixed, or the retina may be diffusely

infiltrated.

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Optic nerve invasion may occur, with spread of tumour along

the subarachnoid space to the brain.

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Metastatic spread is to regional nodes, lung, brain and bone.

Flexner?Wintersteiner Rosettes

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Endophytic growth

Optic nerve infiltration
Types of retinoblastoma

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1. Heritable (hereditary, germline) retinoblastoma accounts for

40%.

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One of the pair of alleles of RB1 is mutated in all the cells in the body.
When a further mutagenic event (`second hit' according to the `two-hit'

hypothesis proposed by Knudson) affects the second allele, the cell may

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then undergo malignant transformation.

Because of the presence of the mutation in all cells, a large

majority of these children develop bilateral and multifocal

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tumours.

Pinealoblastoma (`trilateral retinoblastoma', which occurs in

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up to 10%, usually before the age of 5),

Osteosarcomas,
Soft tissue sarcomas and melanomas
The risk of a second malignancy is about 6%

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Increases five-fold if external beam
irradiation has been used to treat the original tumour,
The second tumour tends to arise within the irradiated field.

2. Non-heritable (non-hereditary, somatic) retinoblastoma.

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60% Cases
The tumour is unilateral,
Non transmissible and
Does not predispose the patient to second non-ocular cancers.
If a patient has a solitary retinoblastoma and no positive

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family history, Its very likely that

Non-heritable
The risk in each sibling and the patient's offspring is about

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1%.

Screening of at-risk family members.
Siblings at risk of retinoblastoma should be screened by

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Prenatal ultrasonography,
Ophthalmoscopy soon after birth and
Then regularly until the age of 4 or 5 years.
Early diagnosis correlates with a higher chance of preserving

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vision, salvaging the eye and preserving life.

If a child has heritable retinoblastoma, the risk to siblings is

2% if the parents are healthy, and 40% if a parent is affected.

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Parents should also be screened

Clinical features
Bilateral cases present with in 1 yr of age

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Unilateral cases present up to 2 yrs of age
Leukocoria (white pupillary reflex) is the commonest

presentation (60%) and may first be noticed in family

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photographs.


Leukocoria

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Strabismus is the second most common (20%); fundus

examination is therefore mandatory in all cases of childhood

squint.

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Painful red eye with secondary glaucoma
Painful red eye with uveitis
Poor vision.
Inflammation or pseudoinflammation

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Nystagmus


Uveitis

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Iris nodules with pseudohypopyon


Clinical features
Routine examination of a patient known to be at risk.

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Orbital inflammation mimicking orbital or preseptal
cellulitis may occur with necrotic tumours

Orbital invasion or visible extraocular growth

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Metastatic disease involving regional lymph nodes
and brain before the detection of ocular involvement is
rare.

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Orbital cel ulitis


Orbital invasion

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Signs
An intraretinal tumour

is a homogeneous,

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dome-shaped white

lesion that becomes

irregular, often with

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white flecks of

calcification.

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Signs
An endophytic tumour

projects into the

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vitreous as a white mass

that may `seed' into the

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gel.

Signs
An exophytic tumour

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forms multilobular

subretinal white

masses and causes

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overlying retinal

detachment
Clinical Stages

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I. Quiescent stage.
II. Glaucomatous stage.
III. Stage of extraocular extension.
IV. Stage of distant metastasis.

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Clinical Stages
I. Quiescent stage.
Lasts for about 6 months to1year.
Leukocoria
Nystagmus

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Strabismus
Diminution of vision
Retinal detachment

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Clinical Stages
II. Glaucomatous stage.
Pain, redness, watering.
Eyeball is enlarged leading to

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proptosis.

Conjunctival congesion.
Corneal haze.
Increased intraocular pressure.

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Rarely acute iridocyclitis.

Clinical Stages
III. Stage of extraocular

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extension.

Fungation and involvement

of extraocular tissues

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resulting in marked

proptosis
Clinical Stages

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IV. Stage of distant metastasis.
1. Lymphatic spread to preauricular and neighbouring lymph

nodes.

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2. Direct extension by continuity to the optic nerve and brain

is common.

3. Metastasis by blood stream involves cranial and other

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bones.

Investigations

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Red reflex testing with a distant direct ophthalmoscope
Examination under anaesthesia
General examination
Tonometry.
Measurement of the corneal diameter

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Anterior chamber examination
Ophthalmoscopy,
Cycloplegic refraction.

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Investigations
Ultrasonography
Aqueous LDH levels
Wide field photography
CT scan

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MRI for optic nerve evaluation
Bone scans and bone marrow aspiration
Genetic study

USG

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B Scan displays a

caulifiower like mass

arising from the retina.

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A scan through the mass

shows a characteristic V-Y

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pattern.


CT SCAN

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Differential diagnosis
Persistent anterior fetal vasculature (persistent

hyperplastic primary vitreous)

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Coats disease
Retinopathy of prematurity
Toxocariasis
Uveitis
Vitreoretinal dysplasia

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Endophthalmitis
Treatment
1. Tumour destructive therapy.
When tumour is involving less than half of retina and optic

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nerve is not involved

Chemoreduction followed by local therapy
(Cryotherapy, thermochemotherapy or brachytherapy) for

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large tumours (>12mm in diameter)

Tumour <12 mm in diameter and <8mm in thickness

Radiotherapy (external beam radiotherapy or brachytherapy)

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combined with chemotherapy is recommended for medium

size.

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Cryotherapy is indicated for a small tumour (<4.5 mm

indiameter and <2.5 mm in thickness) located anterior to

equator.

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Laser photocoagulation is used for a small tumour located

posterior to equator <3 mm from fovea.

Thermotherapy with diode laser is used for a small tumour

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located posterior to equator away from macula

2. Enucleation
Tumour involves more than half of the retina.

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Optic nerve is involved.
Glaucoma is present and anterior chamber is involved.
Followed by radiotherapy and chemotherapy if optic nerve is

involved.

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Intravenous carboplatin, etoposide and vincristine (CEV) are

given in three to six cycles according to the grade of

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retinoblastoma.
Careful review at frequent intervals is generally required

following treatment, in order to detect recurrence or the

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development of a new tumour, particularly in heritable

disease.

Palliative therapy

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Retinoblastoma with orbital extension,
Retinoblastoma with intracranial extension, and
Retinoblastoma with distant metastasis.

Chemotherapy,

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Surgical debulking of the orbit or orbital exentration, and
External beam radiotherapy
Prognosis
If untreated the prognosis is almost always bad and the

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patient invariably dies.

Rarely, spontaneous regression with resultant cure and
shrinkage of the eyeball may occur due to necrosis followed

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by calcification

Prognosis is fair (survival rate 70-85%) if the eyeball is

enucleated before the occurrence of extraocular extension.

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MCQs
1. Gene Rb1 responsible for retinoblastoma is located at:
A. 13q14
B. 14q13

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C. 13p14
D. 14p13
MCQs
2. Pathognomic feature of retinoblastoma is:
A. Necrosis

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B. Calcification
C. Granulomatous reaction
D. None

MCQs

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3. Characteristic histopathological feature of retinoblastoma is:
A. Flexner?Wintersteiner rosettes,
B. Granulomatous reaction
C. Homer?Wright and fleurettes
D. None

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4. On A scan characteristic pattern of Retinoblastoma is:
A. Collar stud appearance
B. V-Y Pattern
C. Cauliflower pattern
D. All

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5. The most common clinical presentation of retinoblastoma is:
A. Nystagmus
B. Leukocoria
C. Strabismus

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D. Secondary glaucoma
6. Which not a clinical presentation of Retinoblastoma
A. Nystagmus
B. Leukocoria
C. Strabismus

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D. Growth retardation

7. Which not a differential diagnosis for Retinoblastoma
A. Coat's disease
B. Persistent hyperplastic primary vitreous

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C. Endophthalmitis
D. Central retinal vein occlusion
8. Leucocoria is seen in:
A. Cataract
B. Coat's disease

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C. Retinopathy of prematurity
D. All

9. If retinoblastoma involves more than half of the retina, the

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treatment of choice is:

A. Chemotherapy
B. External beam radiotherapy
C. Enuclaetion

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D. Cryotherapy
10. The most preferred combination of chemotherapy for

retinoblastoma is:

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A. Methotrexate, etoposide & vinblastin
B. Methotrexate, etoposide & vincristin
C. Carboplatin, etoposide & vinblastin
D. Carboplatin, etoposide & vincritin

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Thank You