Case 1
A 19-month-old boy with a medical history of malrotation of the intestines
who had recently undergone their surgical repair, was referred for evaluation
of leukocoria in his right eye. His ocular history was significant for strabismus
at 6 months of age that was attributed to prominent epicanthal folds. At approximately
19 months of age, his right eye clearly deviated, and he was referred to a
pediatric ophthalmologist who subsequently referred the patient to the ocular
oncology unit at the University of California, San Francisco (UCSF).
On examination at UCSF, the patient demonstrated visual fixation that
was not central and not steady in the right eye, with central steady and maintained
fixation in the patient's left eye. A 15–prism diopter (PD) exotropic
strabismus was observed in the right eye. Intraocular pressures were 19 mm
Hg OD and 21 mm Hg OS.
Indirect ophthalmoscopy performed under anesthesia revealed an elevated
exophytic mass in the right inferotemporal retina, measuring 10 x 11
x 8 mm (Figure 1). The subretinal
mass, which appeared yellow and lipid filled, was associated with a total,
exudative retinal detachment. Scattered subretinal lipid, as well as retinal
pigment epithelial change, was found throughout the retina. The majority of
the retinal vasculature appeared normal, although prominent telangiectatic
vessels, confirmed by intraoperative fluorescein angiography, were noted overlying
the tumor mass. No intrinsic calcification of the mass was noted on ultrasonography.
The left eye demonstrated a normal disc, vessels, macula, and periphery.
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Figure 1. Yellow subretinal mass with associated
subretinal fluid and scattered subretinal lipids.
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Orbital and cerebral computed tomographic scans demonstrated right microophthalmia,
with a noncalcified minimally enhancing nodular mass along the posterior wall
of the right orbit, as well as focal subependymal calcifications. Magnetic
resonance imaging revealed cortical tubers and subependymal hamartomas within
the brain parenchyma. No giant cell astrocytoma was noted. These radiographic
findings were believed to be characteristic of tuberous sclerosis.
The patient was noted as having diffuse ash-leaf spots on dermatologic
examination (Figure 2). Infectious
serologies for toxoplasmosis, rubella, cytomegalovirus, herpes simplex virus
type 1, and herpes simplex virus 2 were negative.
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Figure 2. Hypopigmented macules consistent
with the clinical appearance of ash-leaf spots.
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The differential diagnosis included retinal astrocytoma, Coats disease,
persistent hyperplastic primary vitreous, or an atypical presentation of retinoblastoma.
Subsequent examination of the right eye was remarkable for an intraocular
pressure of 53 mm Hg, iris neovascularization, and a total retinal detachment.
The right eye was enucleated and replaced with a hydroxyapatite implant. Pathologic
examination results revealed necrotic retinoblastoma with a secondary Coats-like
response. There was no involvement of the optic nerve. To date, this child
has remained free of retinoblastoma in the orbit and in the contralateral
eye for 26 months. The patient was referred to a pediatric neurologist for
management of tuberous sclerosis with central nervous system involvement.
The child remains asymptomatic from this disease process.
Case 2
A previously healthy 6-year-old boy who had undergone an undiagnostic
anterior chamber and vitreous tap in Ecuador was referred to UCSF for further
consideration of a mass in his right globe. Findings from an extensive workup
for infectious disease performed in Ecuador were negative. He had been given
a preliminary diagnosis of Coats disease.
He first visited UCSF under a regimen of topical fluorometholone and
atropine for his right eye. On examination, his visual acuity was no light
perception OD and 20/20 OS. Leukocoria was present in the right eye. Slitlamp
examination of his right eye was remarkable for shallow and inferior iridocorneal
adhesions, a neovascularized iris, and retrolenticular opacification in the
anterior vitreous. Intraocular pressure was 45 mm Hg OD. Indirect ophthalmoscopy
revealed a detached and diffusely thickened retina without a visible focal
mass. Ultrasonography confirmed a detached retina with rare intraretinal calcification
and no focal mass lesion. Computed tomographic scans demonstrated high attenuation
of the right vitreous, suggesting that the vitreous was filled with proteinaceous
material. Additionally, 2 calcifications were seen within the anterolateral
aspect of the globe.
The differential diagnosis included Coats disease with dystrophic calcification;
however, given the results of the diagnostic studies, retinoblastoma could
not be excluded. With no light perception visual acuity and rapidly increasing
intraocular pressure, the blind eye was enucleated.
Pathologic inspection revealed diffuse retinoblastoma with an extensive
necrotic tumor. Focal areas of calcification invaded the optic nerve but did
not extend posterior to the lamina cribrosa. Results of a full metastatic
workup were negative; however, since this child had previously had a drainage
procedure and an anterior chamber tap, the UCSF tumor board recommended 6
months of adjuvant chemotherapy. The boy completed 6 cycles of combination
carboplatin, etoposide, and vincristine, which he tolerated well. He has relocated
to the United States and receives regular follow-up monitoring. To date, after
32 months of follow-up, he continues to be without evidence of retinoblastoma
recurrence.
Case 3
A previously healthy 9-year-old girl visited her ophthalmologist with
a retinal detachment following trauma to her left eye from a baseball. She
was found to have a solid retinal detachment with white flocculent material
under the retina and within the vitreous cavity, though she denied having
any visual symptoms. A review of family photographs showed evidence of left
eye leukocoria lasting for 30 months.
Examination at UCSF demonstrated a visual acuity of 20/20 OD and no
light perception OS. Intraocular pressures were 16 mm Hg OD and 20 mm Hg OS.
Slitlamp examination showed diffuse rubeosis iriditis in the left eye, as
well as snow-white material in the vitreous that aggregated into clumps and
was without intrinsic vasculature (Figure
3). A shallow and diffuse retinal detachment was observed posteriorly.
On fluorescein angiography, a posterior tumor mass was noted in the left eye,
along with vitreous opacities and iris rubeosis. Ultrasonography failed to
demonstrate any intrinsic calcification.
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Figure 3. Slitlamp photograph of vitreous
cells as the clinical presentation of retinoblastoma in a 9-year-old.
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During examination while the patient was under anesthesia, neither normal
retinal structures nor the optic nerve could be visualized. The vitreous demonstrated
a confluent ocular process that had the appearance of inflammation, but that
potentially represented vitreous seeding from retinoblastoma.
Computed tomographic scans demonstrated a high-density mass involving
her posterior and superolateral left globe. The mass was without intrinsic
calcification and was thought unlikely to be a retinoblastoma, especially
in light of the child's advanced age.
The differential diagnosis included a massive reaction in the vitreous
cells to an inflammatory or infectious process vs retinoblastoma. Since the
eye was blind as a result of iris neovascularization, an enucleation was performed.
Pathologic inspection revealed necrotic retinoblastoma cells, which
spared the choroid but invaded the optic nerve posterior to the lamina cribrosa.
Results of a systemic workup for metastasis were negative. The patient's case
was presented to the UCSF tumor board, which recommended adjuvant chemotherapy.
She underwent a 6-month course of carboplatin, etoposide, and vincristine,
and to date, she has been without recurrence for 16 months.
Comment
Atypical cases of retinoblastoma may lead to diagnostic dilemmas. In
the first case, a 19-month-old boy was referred for leukocoria. The diagnosis
of retinoblastoma was complicated by magnetic resonance imaging findings consistent
with tuberous sclerosis. This made the possibility of an intraocular astrocytic
hamartoma likely, since approximately half of all patients with tuberous sclerosis
demonstrate retinal hamartomas.1 Atypical
retinal astrocytomas with peculiar neovascularization have been reported.2 The eye was also judged to be small, involving
persistent hyperplastic primary vitreous in the differential diagnosis. The
clinical presentation, however, was most consistent with Coats disease, and
retinoblastoma with a prominent Coats-like response was confirmed by the pathology
report. No evidence of intrinsic calcification was found within this tumor.
In the second case, a 6-year-old boy was referred from Ecuador with
a diagnosis of Coats disease. The results of clinical imaging scans at UCSF
suggested proteinaceous material within the vitreous and no focal tumor mass.
However, the presence of calcification on computed tomographic scans, which
could have been consistent with dystrophic calcification in Coats disease,
increased suspicion for retinoblastoma. Use of contrast magnetic resonance
imaging has increased the sensitivity in distinguishing Coats disease from
retinoblastoma.3 Enhancement of detached
sensory retina with the absence of intraocular enhancement following gadolinium–diethylenetriamine
pentaacetic acid (DPTA) treatment favors a diagnosis of Coats disease.4 Some difficulty remains, however, in differentiating
retinoblastoma from advanced Coats disease.5
Despite the older age at presentation, retinoblastoma was confirmed histopathologically.
He unfortunately underwent 6 months of adjuvant chemotherapy because of the
procedure that was performed in Ecuador.
In the third case, a 9-year-old girl had a clinical appearance suggestive
of uveitis. The cellular material that filled the vitreal space showed no
intrinsic calcification and was without intrinsic vascularity. Because the
child was 9 years old at the time of examination, retinoblastoma was, again,
a relatively low consideration. Although retinoblastoma becomes less frequent
with older age, it has been described in adult populations.6
Should this child have demonstrated effective vision, a vitreous aspirate
and biopsy (as recommended by several retina specialists) could have been
performed. Children with retinoblastoma undergoing intraocular procedures
may require bone marrow transplantation for cure. Even with aggressive treatment,
many succumb to disseminated disease once the integrity of the globe has been
violated by an intraocular procedure.
In summary, the treating ophthalmologist should retain a high index
of suspicion for retinoblastoma in all children with intraocular disease,
even those who present with an atypical appearance or at an advanced age.
Children with no view of the posterior pole who have histories of trauma and
hyphema may harbor occult retinoblastoma. Children with uveitic or Coats-like
scenarios may also represent unusual manifestations of this disease. Unless
retinoblastoma is considered, improper actions may be undertaken, resulting
in a potential increase in morbidity and mortality for patients with this
disease.
Sharon McCaffery, MD;
Mark R. Wieland, MD;
Joan M. O'Brien, MD
San Francisco, Calif
Kim L. Cooper, MD;
Mark R. Wieland, MD
Stanford, Calif
Robert T. Wendel, MD
Davis, Calif
Corresponding author: Joan M. O'Brien, MD, Ocular Oncology Division,
Department of Ophthalmology, University of California San Francisco, 10 Koret
Way, Room K-301, Box 0730, San Francisco, CA 94143-0730 (e-mail: aleja{at}itsa.ucsf.edu).
REFERENCES
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ABSTRACT
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hemorrhage in a patient with tuberous sclerosis. Retina. 1986;6:53-56.
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of Gd-DTPA contrast enhancement. Radiol Clin North Am. 1998;36:1101-1117.
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4. Edward DA, Mafee MF, Garcia-Valenzuela EG, Weiss RA. Coats' disease and persistent hyperplastic primary vitreous: role of
MR imaging and CT. Radiol Clin North Am. 1998;36:1119-1131.
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5. Steidl SM, Hirose T, Sang D, Hartnett ME. Difficulties in excluding the diagnosis of retinoblastoma in cases
of advanced Coats' disease: a clinicopathologic report. Ophthalmologica. 1996;210:336-400.
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6. Biswas J, Mani B, Shanmugam MP, et al. Retinoblastoma in adults: report of three cases and review of the literature. Surv Ophthalmol. 2000;44:409-414.
PUBMED
SECTION EDITOR: W. RICHARD GREEN, MD
