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Clinicopathologic Reports, Case Reports, and Small Case Series
June 2002

Mushroom-Shaped Choroidal Recurrence of Retinoblastoma 25 Years After Therapy

Arch Ophthalmol. 2002;120(6):844-846. doi:

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.

Report of a Case

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 choroidal melanoma.

Figure 1
 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
body region.

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 body region.

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.

Figure 2
 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).

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).

Comment

Whole-eye radiotherapy for retinoblastoma offers tumor control in 41% to 74% of cases.14 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 group).

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.

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