Nelson Textbook http://ebookdokter.blogdetik.

com
of Pediatrics KU / 10600
CHAPTER 455 RETINOBLASTOMA
RETINOBLASTOMA
Charles B. Pratt

This tumor occurs in about 1 in 16,000 live births in the United States, with a similar
incidence among black and white children. The median age at diagnosis is 11 mo for
patients with bilateral tumors and 23 mo for those with unilateral tumors. About 30% of
patients with retinoblastoma have bilateral involvement and a dominantly inherited
predisposition to the malignancy. Genetic predisposition also occurs in about 20% of
patients with unilateral disease. The finding that retinoblastoma occurred in patients with
"13q{endash}– syndrome" (characterized by growth delay, mental retardation, and facial
and other anomalies) helped to localize the retinoblastoma gene to the long arm of
chromosome 13 (see Chapter 446).
The Rb gene also carries an increased risk of other tumors. For example, in about 1% of
the survivors of the hereditary form of retinoblastoma, osteosarcoma will develop by
about 10 yr of age. These osteosarcomas may occur at an irradiated site or at a
nonirradiated site and are sometimes multifocal. It is estimated that 30% of individuals
cured of the hereditary form of retinoblastoma will have a second malignancy within 30
yr. In trilateral retinoblastoma syndrome, pineal tumors that are histologically similar to
retinoblastoma develop in patients with bilateral ocular disease.

PATHOLOGY.

Retinoblastoma usually develops in the posterior portion of the retina. The tumor
consists of small, round, closely packed malignant cells with scanty cytoplasm. Rosette
formation occurs, possibly reflecting an abortive attempt at formation of rod and cone
cells.
Retinoblastoma may appear as a single tumor in the retina but typically has multiple foci.
When it arises in the internal nuclear layers of the retina, it grows forward into the
vitreous cavity. This endophytic growth is easily seen with the ophthalmoscope.
Exophytic tumors (arising in the external nuclear layer and growing into the subretinal

1
Nelson Textbook http://ebookdokter.blogdetik.com
of Pediatrics KU / 10600
space, with detachment of the retina) are hidden, and the diagnosis is more difficult.
Tumor fragments may break off from endophytic tumors and float free in the vitreous to
"seed" other parts of the retina. Vitreous seeding is associated with large tumors (usually
more than 5 disc diameters) and a poor prognosis. Extension of retinoblastoma into the
choroid usually occurs with massive tumors and may indicate an increased likelihood of
hematogenous metastases. Extension of tumor through the lamina cribrosa and down the
optic nerve may lead to central nervous system involvement. Both choroidal and optic
nerve invasion increase the risk of metastatic disease.
Because these tumors rarely metastasize before they are detected, the primary concern at
diagnosis is generally preservation of useful vision. Accordingly, retinoblastoma is staged
by the extent of disease within the eye.

CLINICAL MANIFESTATIONS.

Retinoblastoma usually presents with leukocoria, a yellowish white reflex in the pupil
caused by tumor behind the lens. Other common findings include diminished or absent
vision and strabismus. With more advanced tumor, pupillary irregularity, hyphema, and
pain may be present. Proptosis, signs of increased intracranial pressure, or bone pain may
occur with very advanced or metastatic disease.
More than 80% of patients with hereditary retinoblastoma have tumors involving both
eyes at the time of diagnosis. Multifocal disease involving a single globe is also
associated with the hereditary form of retinoblastoma. Asynchronous involvement of
both globes rarely appears after 18 mo of age. In the case of familial retinoblastoma, the
disease may be discovered on routine funduscopic examination of the offspring or sibling
of a patient who has had the disease.
DIAGNOSIS. The finding of leukocoria must be followed by a careful funduscopic
examination, which usually requires anesthesia in children. Computed tomographic scan
of the orbits should be performed to evaluate the extent of tumor and to assess whether
optic nerve or bony structures are involved. Magnetic resonance imaging is of greater
value in defining optic nerve invasion. Most intraocular retinoblastomas show evidence
of intratumoral calcification. Ultrasonography may aid in the differential diagnosis,

2
Nelson Textbook http://ebookdokter.blogdetik.com
of Pediatrics KU / 10600
which includes other causes of leukocoria such as retinal detachment, persistent
hyperplastic primary vitreous, nematode endophthalmitis (ocular larva migrans), bacterial
panendophthalmitis, cataract, coloboma of the choroid, and retinopathy of prematurity.
Radionuclide bone scan and examinations of the bone marrow and cerebrospinal fluid for
tumor cells are not necessary unless there is physical, radiographic, or histopathologic
evidence of extraocular extension. Elevated plasma levels of carcinoembryonic antigen
are rarely found at the time of diagnosis; a subsequent rise in levels may indicate
recurrence of tumor.

TREATMENT.

The standard treatment for unilateral disease is enucleation, although other measures
such as cryotherapy and external beam irradiation may be more appropriate for single or
multiple small lesions. If the tumors are so small that useful vision might be preserved,
irradiation may be preferred. In unilateral disease, however, tumors this small are rare.
For patients with bilateral disease, attempts should be made to salvage useful vision in at
least one eye by using radiotherapy and/or cryotherapy. Radiation may be given
bilaterally from the outset because the eye that appears to be more involved may have a
more dramatic response and be more salvageable. On the other hand, if an eye is so
heavily involved that no useful vision remains or if painful glaucoma has developed as a
complication, then enucleation is indicated. When enucleation is done, an attempt should
be made to resect as much of the optic nerve as possible (10 mm or more). Radiation
therapy to the orbit should also be considered if regional extraocular extension of the
tumor has been found at the time of enucleation. Radiation therapy requires daily
sedation and perhaps daily anesthesia.
Chemotherapy confers no definite benefit in patients whose tumors are localized to the
globe. If there is gross or microscopic residual disease in the orbit after enucleation, then
chemotherapy with a combination regimen (probably including cyclophosphamide and
doxorubicin) should be considered along with radiotherapy. Widespread metastatic
disease responds to chemotherapy, although cure is unlikely. Chemotherapy should also

3
Nelson Textbook http://ebookdokter.blogdetik.com
of Pediatrics KU / 10600
be considered for patients whose tumors extensively involve the choroid, sclera, or ciliary
body.

PROGNOSIS.

The overall survival rate is more than 90%, although survival into the 3rd and 4th
decades of life may be decreased considerably by the high incidence of second
malignancies. Cures are infrequent for patients with massive orbital disease or extensive
optic nerve involvement at diagnosis, who are likely to have intracranial spread and
distant metastases. If microscopic examination reveals tumor in the periglobal tissues of
the optic nerve, there is a slight chance of long-term survival with irradiation and
chemotherapy.