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Copyright 2001 American Medical Association. All Rights Reserved.
Applicable FARS/DFARS Restrictions Apply to Government Use.2001
The occurrence of a midline intracranial primitive neuroectodermal tumor
(PNET) with bilateral retinoblastoma has been called "trilateral retinoblastoma."1 This rare complication of heritable retinoblastoma
is associated with an extremely poor prognosis, accounting for up to 50% of
tumor-associated mortality among patients with retinoblastoma.2
Primitive neuroectodermal tumors usually occur 2 to 4 years after diagnosis
of bilateral retinoblastoma. However, PNETs have been diagnosed in patients
with unilateral retinoblastoma 6 months before diagnosis of bilateral retinoblastoma
and in 2 siblings of patients with bilateral retinoblastoma with no intraocular
disease.3 In most cases, patients with PNET
are seen for symptoms of increased intracranial pressure after the tumor is
large, and the disease is usually fatal.3
Patients diagnosed with small, asymptomatic PNETs, however, have improved
survival rates when treated with chemotherapy and radiation.4
This has led to routine neuroimaging among patients with heritable retinoblastoma
to detect preclinical intracranial neoplasms in many centers. However, no
studies have established which patients are most likely to benefit from routine
neuroimaging, how often patients should be screened, or whether routine neuroimaging
improves patient outcome.
Of 226 patients with retinoblastoma evaluated between January 1990 and
December 1998 at 2 large referral centers, the University of California, San
Francisco, and Bascom Palmer Eye Institute, Miami, Fla, we identified 3 patients
A 3½-month-old girl had bilateral retinoblastoma, Reese-Ellsworth
stage IIB in the right eye and stage VA in the left. Her family history was
remarkable for retinoblastoma. Initial computed tomographic (CT) scan showed
no extraocular or intracranial disease. The left eye was enucleated. At age
38 months, chemotherapy was initiated for a recurrent tumor in the right eye
after treatment with cryotherapy and laser. Despite multiple cycles of chemotherapy,
the tumor progressed with diffuse vitreous seeding. At age 55 months, the
right eye was enucleated. Findings from histopathologic examination demonstrated
well-differentiated retinoblastoma confined to the globe. Routine magnetic
resonance images (MRIs) of the brain and orbits were obtained every 5 months.
At age 60 months, the patient complained of headaches. An MRI scan of the
brain and orbits showed no evidence of intracranial disease. At age 62 months,
the patient was seen for displacement of the right prosthesis. An MRI demonstrated
a new extraconal mass in the right orbit (Figure 1). The mass was felt to be an orbital PNET rather than recurrent
retinoblastoma because it was external to dural reflections in the orbit seen
on MRI scan. Fine-needle aspiration biopsy revealed a poorly differentiated
round blue cell tumor consistent with PNET. Metastatic evaluation disclosed
no other evidence of tumor. Despite prompt exenteration, chemotherapy, and
radiation, the patient died 9 months after PNET diagnosis.
Case 1. A magnetic resonance image
in a 62-month-old patient with bilateral retinoblastoma demonstrated a new
extraconal mass in the right orbit. The mass was felt to be an orbital primitive
neuroectodermal tumor because it was external to dural reflections in the
A 7-week-old girl with no family history of retinoblastoma was seen
for unilateral retinoblastoma (Reese-Ellsworth stage VA) in the left eye.5 Initial CT scan showed no extraocular or intracranial
disease. The left eye was enucleated. Results of histopathologic examination
demonstrated well-differentiated retinoblastoma confined to the globe. The
patient was examined under anesthesia every month for 2 months, then every
2 months for 6 months, then every 3 months, and did not develop retinoblastoma
in the right eye. At age 22 months, the patient developed nausea and vomiting.
An emergent CT scan demonstrated a tumor in the pineal region consistent with
PNET (Figure 2). Despite chemotherapy,
the patient died 4 months after PNET diagnosis.
Case 2. A computed tomographic
scan of the brain performed without contrast at age 22 months demonstrated
a tumor in the pineal region, consistent with primitive neuroectodermal tumor.
An 18-month-old girl with no family history of retinoblastoma was seen
for 4 months of unilateral leukocoria in the left eye. Findings on examination
revealed Reese-Ellsworth stage VB retinoblastoma in the left eye and no disease
in the right eye. A CT scan showed no extraocular or intracranial disease.
The left eye was enucleated. Results of histopathologic examination demonstrated
well-differentiated retinoblastoma confined to the globe. The patient underwent
examination with anesthesia. At age 21 months, the patient developed unremitting
headaches. An emergent MRI showed a tumor in the pineal region, consistent
with PNET. Following chemotherapy and radiation, the patient remained without
disease 18 months after PNET diagnosis.
In the current study, routine neuroimaging among patients with heritable
retinoblastoma did not lead to presymptomatic diagnosis of PNET in any patient.
At the time of retinoblastoma diagnosis, all patients were screened with CT
of the brain and orbits under anesthesia, without contrast, with 3.75-mm cuts
through the brain and 1-mm cuts through the orbits. Patients with recognized
heritable retinoblastoma (patients with bilateral retinoblastoma or a family
history of retinoblastoma) underwent additional routine MRIs of the brain
and orbits every 6 months. In any patient with new neurologic symptoms, an
MRI of the head was obtained immediately. No family refused neuroimaging studies.
Of 226 patients seen at these institutions over 9 years, 83 had heritable
retinoblastoma and underwent routine neuroimaging every 6 months. The 143
patients with unilateral, unifocal disease and no family history of retinoblastoma
did not undergo routine neuroimaging after the initial baseline study at the
time of retinoblastoma diagnosis. Mean follow-up time was 44.8 months, with
a range of 0 to 139 months.
A limitation of this study is that 56 (25%) of 226 patients were followed
up for less than 2 years, and some of these patients may develop PNET in the
future, during the 2 to 4 years following retinoblastoma diagnosis. In the
current series, 1 of the 86 patients who were screened developed PNET, which
was diagnosed after the patient was seen for symptoms and not as a result
of routine neuroimaging. Two of 3 PNET patients were not recognized to have
heritable retinoblastoma and did not undergo routine neuroimaging.
The current series of 226 patients with retinoblastoma did not demonstrate
improved outcome due to early diagnosis of PNET by routine neuroimaging of
patients with recognized heritable retinoblastoma. Because PNET occurs infrequently,
many patients with retinoblastoma must be studied to investigate the utility
of routine neuroimaging in diagnosing this condition. An international, prospective,
multicenter collaborative trial is necessary to determine the appropriate
regimen for routine neuroimaging in patients with both heritable and presumed
Corresponding author: Joan M. O'Brien, MD, Box 0730, University of
California, San Francisco, San Francisco, CA 94143-0730 (e-mail: email@example.com).
Duncan JL, Scott IU, Murray TG, Gombos DS, van Quill K, O'Brien JM. Routine Neuroimaging in Retinoblastoma for the Detection of Intracranial Tumors. Arch Ophthalmol. 2001;119(3):450–452. doi:
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