Girl presents with unilateral retinal lesion
The gray elevated retinal mass was superotemporal to the macula with overlying focal white opacities consistent with calcification.
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An 8-year-old healthy girl presented to the New England Eye Center retina service for evaluation of a retinal lesion in the right eye.
On a recent routine dilated eye exam, she was found to have a white, elevated retinal mass. Her pediatric ophthalmologist was concerned for retinoblastoma. She had no change in vision and was asymptomatic. She was born full term without complications. She had no ocular history or previous eye surgery or trauma. She did not take medications. Her mother and younger sister recently had normal eye exams, and she had no other known family history of eye disease. She had no neurologic symptoms.
Examination
Visual acuities were 20/20 in both eyes. Pupils were symmetric and briskly reactive to light with no afferent pupillary defect. IOP was 7 mm Hg in the right eye and 8 mm Hg in the left eye. Confrontation visual fields were full in both eyes. Extraocular movements were full in both eyes, and the patient was orthophoric.
Source: Christine Benador-Shen, MD, and Jay S. Duker, MD
Anterior segment exam of both eyes was unremarkable. On dilated fundus exam, she had healthy optic nerves with small cup-to-disc ratios. She had no vitreous cells or opacities. In the right eye, there was a well-demarcated 5 mm by 5 mm, mostly amelanotic, gray elevated retinal mass superotemporal to the macula with overlying focal white opacities consistent with calcification (Figure 1). There was retinal pigment epithelium (RPE) hyperpigmentation and chorioretinal atrophy along the edge of the mass. There was no subretinal fluid and no additional masses in either eye. The retinal vasculature was normal. OCT of the lesion showed a homogenous intraretinal mass with moderate reflectivity, overlying calcification, retinal atrophy, and loss of both the retinal architecture and choriocapillaris (Figure 2). B-scan ultrasound of the right eye demonstrated a retinal lesion with high internal reflectivity and a thickness of 1.26 mm (Figure 3). The left eye was normal.
What is your diagnosis?
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Retinal lesion
Our patient was diagnosed with probable retinocytoma.
The differential diagnosis of an asymptomatic unilateral retinal lesion in a child includes neoplasms such as retinoblastoma, retinocytoma and retinal astrocytic hamartoma. Retinoblastoma was considered but thought less likely because 90% of cases are diagnosed by age 5 years. Retinoblastomas are typically more diffusely calcified and have retinal feeder vessels. RPE changes and chorioretinal atrophy are present only in treated retinoblastoma, and our patient had no history of treatment. The calcification in retinal astrocytoma is yellow and has a “fish egg” appearance, which was not seen in her case. In addition, astrocytomas have disorganized but preserved retinal layers on OCT.
The differential also includes amelanotic choroidal melanoma and choroidal osteoma, which are see in older patients. Choroidal melanoma is localized to the choroid and has low to medium internal reflectivity on ultrasound. Choroidal osteoma is a highly calcified choroidal tumor often adjacent to the optic nerve with high internal reflectivity on B-scan ultrasound and characteristic shadowing. Our patient’s lesion did not resemble these neoplasms. Coats’ disease, persistent fetal vasculature and ocular toxocariasis can present as a unilateral white mass in a child but are less likely in a patient older than 5 years.
Given our patient’s lack of family history and unilateral mass, the underlying mutation was thought to be sporadic. Although it was recommended, her parents elected to not have genetic testing yet. MRI of the brain was performed to evaluate for pineoblastoma. Imaging revealed a 1 mm by 1 mm T2 hyperintense cystic lesion in the pineal gland consistent with a pineal cyst. Neurosurgery reviewed these findings and thought the probability of a primitive neuroendocrine tumor was low.
Discussion
Retinocytoma is now regarded to be a benign and well-differentiated form of retinoblastoma. The causative RB1 mutation can be germline or somatic. In the two-hit hypothesis, retinoblastoma develops when the second hit occurs in an undifferentiated retinal cell, while in retinocytoma this occurs in a partially differentiated retinocyte. Because its appearance is similar to that of radiation-treated retinoblastoma, retinocytoma was initially thought to be spontaneously regressed retinoblastoma. In a retrospective case series studying 920 patients with retinoblastoma, retinocytoma or both, the rate of retinocytoma was 1.8%. The median age of diagnosis was 15 years but ranged from 4 to 45 years. In contrast to retinoblastoma, retinocytomas have bland cells with no necrosis or mitoses. Retinocytomas may undergo malignant transformation to retinoblastoma at a rate of 4% to 12%. Several studies have reported adult-onset retinoblastoma, which may have originated from an undiagnosed retinocytoma that underwent malignant transformation.
Patients are often asymptomatic. Many retinocytomas are discovered during a routine eye exam or in family members of patients with retinoblastoma. Vision is variably affected depending on the location of the tumor. Some patients present with strabismus. On exam, retinocytoma is classically a gray, translucent retinal mass with calcification and RPE pigment changes. All three of these features were present in 33% of retinocytomas in the case series mentioned above. Chorioretinal atrophy was also present in 54%. Of these tumors, about 30% were located in the macula while 70% were located in the periphery. Our patient’s exam was typical and had all four features.
The diagnosis of retinocytoma is made based on its characteristic appearance and supported by older age at diagnosis and family history of retinocytoma or retinoblastoma. An important differentiating factor between retinocytoma and retinoblastoma is its lack of growth over 4 to 6 weeks and stability over time. OCT of the tumor demonstrates an elevated homogenous mass with loss of retinal architecture and absent choriocapillaris. If calcification is present, B-scan ultrasound will show a mass with high internal reflectivity. Families should undergo genetic counseling and testing to discuss the risk for inheritance in future offspring. Unilateral retinocytoma with retinoblastoma in the fellow eye has the same genetic risk as bilateral retinoblastoma. Additionally, MRI of the brain should be performed to evaluate for pineoblastoma, which is associated with both retinocytoma and retinoblastoma.
Treatment for retinocytoma involves close observation with an initial exam interval of 4 to 6 weeks to ensure there is no tumor growth. Tumor size and depth can be documented using serial fundus photography, OCT and B-scan ultrasound. If stable, the examination interval can be increased. In one study, the longest duration of stability without treatment was 28 years. However, it is crucial that patients with retinocytoma have lifelong follow-up due to the risk for malignant transformation into retinoblastoma. Any evidence of tumor growth should prompt treatment of the lesion as a retinoblastoma.
Clinical course continued
Our patient was reexamined 4 weeks later and had a stable exam. Her visits have been spaced out to every 6 months. Her visual acuities remain 20/20 in both eyes. Over a period of 2 years, the lesion has not grown in size, and there is no development of subretinal fluid. She has no new retinal masses in either eye.
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- For more information:
- Christine Benador-Shen, MD, and Jay S. Duker, MD, can be reached at New England Eye Center, Tufts University School of Medicine, 800 Washington St., Box 450, Boston, MA 02111; website: www.neec.com.
- Edited by Christine Benador-Shen, MD, and Malgorzata Dymerska Peterson, MD. They can be reached at New England Eye Center, Tufts University School of Medicine, 800 Washington St., Box 450, Boston, MA 02111; website: www.neec.com.