An important method of conservative therapy for retinoblastoma during
the past 50 years has been external beam radiotherapy. In general, this modality
offers favorable tumor control, but subsequent monitoring for local recurrence
and application of salvage therapy have been emphasized. Several authors have
observed that recurrence is usually detected within 1 year of therapy.1,2 We report late-onset choroidal
recurrence of retinoblastoma 25 years following therapy.
A 25-year-old Latin American woman noticed sudden, painless visual loss
in her only eye on awakening. Visual acuity was hand motions OD; the left
eye had been enucleated. She gave a history of bilateral sporadic retinoblastoma
diagnosed at age 12 months and managed initially with chemotherapy and cryotherapy
to the right eye and enucleation of the left eye. One year later, 2 tumor
recurrences were detected at the site of previous cryotherapy scars superiorly
and inferonasally, measuring 1.5 × 1.5 × 1.0 mm and 12.0 ×
10.5 × 8.0 mm, respectively. The inferonasal mass displayed vitreous
seeds and the eye was classified as Reese-Ellsworth group Vb. External beam
radiotherapy using 3500 rad was delivered through an anterior portal. A cataract
was subsequently removed. During the following 24 years, the tumors were followed-up
elsewhere and remained regressed. Examination under anesthesia with complete
funduscopy was performed for 9 consecutive years and office evaluation for
the subsequent 15 years. Radiation complications of maculopathy, dry eye,
and corneal opacification combined with photophobia afforded a poor view of
the fundus during those 15 years.
At the most recent examination, there was a hyphema and vitreous hemorrhage
that precluded a view of the fundus. The patient was referred to the Ocular
Oncology Service at Wills Eye Hospital (Philadelphia, Pa) for further management.
Results of ocular ultrasound revealed a mushroom-shaped fundus mass measuring
15.0 mm in base and 10.3 mm in thickness. There was a slight suggestion of
calcification in the tumor but no acoustic shadowing in the orbit (Figure 1). Vascular pulsations were absent.
Vitreous echoes suggestive of blood were noted. Based on these findings, the
differential diagnosis included late-onset recurrence of retinoblastoma or
B-scan ocular ultrasound of an
eye with no fundus view owing to hyphema and vitreous hemorrhage. Note the
echogenic mushroom-shaped fundus mass in the peripheral choroid and ciliary
The right eye was enucleated. Gross pathology revealed a mushroom-shaped
amelanotic choroidal tumor (Figure 2).
Histopathologic examination results confirmed that the tumor was a poorly
differentiated, mitotically active retinoblastoma forming a massive tumor
in the ciliary body and peripheral choroid (Figure 2). The tumor cells grew in a confluent fashion without necrosis.
The cells had scant cytoplasm and showed intense positive immunoreactivity
for neuron-specific enolase and were negative for S100 protein, consistent
with retinoblastoma. A few calcific foci from a previous scar were noted near
the base of the recurrence. There was tumor invasion of the anterior chamber.
Chemoprophylaxis for metastatic disease was provided using vincristine, etoposide,
and carboplatin for 6 months.
Pathologic examination revealed
an amelanotic mushroom-shaped choroidal mass. A, Gross pathologic appearance
of the retina and retinal pigment epithelium lining the inner surface of the
choroidal mass. B, The choroidal mass is noted with overlying retinal tissue
(hematoxylin-eosin, original magnification ×10). C, Poorly differentiated
retinoblastoma is shown (hematoxylin-eosin, original magnification ×200).
Whole-eye radiotherapy for retinoblastoma offers tumor control in 41%
to 74% of cases.1- 4
When radiotherapy is combined with focal salvage treatments (cryotherapy,
laser photocoagulation, and plaque radiotherapy), tumor control improves to
80%.2 However, tumor control decreases with
more advanced retinoblastoma, such as Reese-Ellsworth group V, where stable
regression is achieved in 29% to 66% of eyes.1,2
Tumor recurrence following external beam radiotherapy generally is detected
within 1 year of treatment2,5
and 96% occurs within 2 years following treatment.1
In an analysis of 65 eyes treated with external beam radiotherapy, all retinoblastoma
recurrences were found within 2.75 years of treatment.1
Tumor recurrence was more likely in slightly older children (1.8 years in
the recurrence group vs 0.9 years in the nonrecurrence group) and in those
with larger tumors (16 mm in the recurrence group vs 8.9 mm in the nonrecurrence
Recurrence of retinoblastoma beyond 4 years following radiotherapy is
extremely rare. Ytteborg and Arnesen6 observed
one case of late-onset recurrence 12 years after radiotherapy. The patient
had shown initial poor tumor control for 2 years following 2 courses of external
beam radiotherapy and subsequent cobalt plaque radiotherapy and xenon photocoagulation.
Recurrence was discovered 10 years after an interval of stable findings. Others
have recognized late recurrence at 4.5 and 9 years.5,7
An alternative possiblity to tumor recurrence in our case could be new
tumor formation in a patient with germinal mutation of the retinoblastoma
gene. In most instances, new tumors in bilateral cases occur within 1 to 2
years from initial diagnosis.8 Late-onset
new tumors after 5 years of follow-up in bilateral retinoblastoma have been
observed at 8 years9 and 12 years.10 Another possibility for the pathogenesis of this
tumor is that it represents a radiation-induced second cancer.11
It seems highly improbable to have retinoblastoma as a second cancer after
treatment of retinoblastoma. In our case, it is most likely that choroidal
recurrence of retinoblastoma developed after 25 years.
Another interesting facet of this case was the configuration of the
recurrence as a mushroom-shaped choroidal mass, suggestive of melanoma with
a rupture through the Bruch membrane.12
The mushroom configuration has rarely been found with nonmelanoma tumors,
such as choroidal metastasis13,14
and choroidal hemangioma,15 that have broken
through the Bruch membrane. To our knowledge, this is the first report of
choroidal invasion from retinoblastoma assuming this configuration. However,
we have seen another case of retinoblastoma histopathologically that had massive
choroidal invasion and had ruptured through the Bruch membrane, assuming a
mushroom configuration. Because of the ultrasound findings, melanoma was a
diagnostic consideration since choroidal melanoma has been reported in association
with both unilateral and bilateral retinoblastoma.11,16
In summary, we report a remarkable case of choroidal recurrence of retinoblastoma
25 years after radiotherapy, that assumed a mushroom shape, simulating a choroidal
melanoma. We advise that patients with retinoblastoma maintain regular monitoring
of the affected eye(s) throughout their lifetimes. If difficulty in visualization
develops owing to media opacity or patient cooperation, then regular ocular
ultrasonography and examination with sedation are warranted.
This research was supported by the Eye Tumor Research Foundation, Philadelphia,
Pa (Dr C. L. Shields), the Paul Kayser International Award of Merit in Retina
Research, Houston Tex (Dr J. A. Shields), and the Noel T. and Sara L. Simmonds
Endowment for Ophthalmic Pathology, Wills Eye Hospital, Philadelphia (Dr Eagle).
Corresponding author and reprints: Carol L. Shields, MD, Ocular Oncology
Service, Wills Eye Hospital, 900 Walnut St, Philadelphia, PA 19107.
Shields CL, Piccone MR, Shields JA, Eagle RC, Singer M. Mushroom-Shaped Choroidal Recurrence of Retinoblastoma 25 Years After Therapy. Arch Ophthalmol. 2002;120(6):844-846. doi: