Uveal melanoma, a life-threatening malignancy, tends to manifest in adults, not children. Although uveal melanoma has been reported in all age groups, including newborns, this tumor occurs at an average age of 58 years.1,2 Based on a large cohort of 8,033 patients treated by the Ocular Oncology Service at Wills Eye Hospital of Thomas Jefferson University in Pennsylvania, uveal melanoma in children younger than 20 years represented only 1% of cases.1 In a similar study from the Ocular Oncology Service at Helsinki University in Finland, where the risk for uveal melanoma supposedly is the highest in the world, the frequency of melanoma in children was nearly the same (0.6% of cases).3
The clinical features and prognosis of uveal melanoma, based on age difference, have been studied.1,3,4 Shields et al. explored clinical features and found that uveal melanomas in children were more likely to show anterior iris location, smaller tumor size, lack of pigmentation, less subretinal fluid, and less frequent extraocular extension.1 A matched cohort study by Kaliki et al. comparing children (< 20 years) with uveal melanoma matched to similar tumors in mid-adults (21 to 60 years) and older adults (> 60 years) identified that younger patients have a better prognosis with lower risk of metastasis.1,4
We describe a 13-year-old girl with choroidal melanoma managed with plaque radiotherapy. We evaluate the published differences in choroidal melanoma clinical features and prognosis between the adult and pediatric population.1–10
A 13-year-old girl noted blurred vision in the right eye and was found to have an intraocular mass. She was referred to the Ocular Oncology Service at Wills Eye Hospital for treatment. On examination, visual acuity was 20/80 in the right eye and 20/20 in the left eye. The left eye was unremarkable. Fundus examination in the right eye revealed a variably pigmented choroidal mass located superior to the macula, measuring 10 mm in basal diameter, and nearly abutting the optic disc and foveola (Figure 1). The mass featured overlying orange pigment confirmed on autofluorescence and subretinal fluid confirmed on optical coherence tomography (OCT). There was no evidence of drusen. Ultrasonography disclosed an acoustically hollow mass with low internal reflectivity, measuring 4.5 mm in thickness (Figure 1). Based on the clinical features and related risk factors, a clinical diagnosis of choroidal melanoma was established (Figure 2).
Choroidal melanoma in a 13-year-old girl. (A) The variably pigmented juxtamacular choroidal tumor is noted with surrounding subretinal fluid. (B) Fundus autofluorescence imaging shows overlying hyperautofluorescence corresponding to orange lipofuscin pigment. The hypoautofluorescence relates to retinal pigment epithelial atrophy. (C) B-scan ultrasonography shows an acoustically hollow, dome-shaped mass of 4.5-mm thickness, consistent with melanoma.
Optical coherence tomography images of choroidal melanoma. (A) Horizontal and (B) vertical imaging cuts showing the abruptly elevated choroidal mass with overlying subretinal fluid and subretinal debris with intraretinal cystoid changes.
The patient underwent custom-designed Iodine-125 plaque radiotherapy using a 15-mm field for apex dose of 7,000 cGy delivered over 96 hours. Sectorial argon laser photocoagulation was performed to the radiation field following radiotherapy to reduce the ischemic load and minimize maculopathy. Intravitreal bevacizumab injection (1.25 mg in 0.05 cc) at the time of plaque removal was provided to reduce vascular endothelial growth factor-related maculopathy.
Choroidal melanoma in children is rare. Most practicing ophthalmologists never witness a case. The mean “age adjusted” incidence of uveal melanoma in the United States is 4.3 per million.5 In the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute, the mean age at presentation of uveal melanoma was 60 years.5 The rate of uveal melanoma in children ages 10 to 14 years was 0.2 cases per million for boys and 0 per million for girls.5 The incidence rates progressively increase up to the age of 70 years, with a peak of 24.5 cases per million in males and 17.8 per million in females.5 Our patient presented at 13 years of age, far below the median age of presentation.3,6,7
Pediatric uveal melanoma can show some characteristic clinical features. A summary of features from several reports is listed in Table 1. In the largest report on childhood uveal melanoma (< 20 years) in 122 cases, the median age at presentation was 16 years.7 In that study, 3% occurred in those ages 0 to 5 years, 11% in those 5.1 to 10 years, 35% in those 10.1 to 15 years, and 50% in those 15.1 to 20 years.7 Although case reports of infants with melanoma are noted, there is strong evidence in the literature that the majority of uveal melanomas develop at or after puberty.
Summary of Reports on Pediatric Uveal Melanoma in the Recent 10 Years
In the case that we report, the tumor measured 10 mm in largest basal diameter and 4.5 mm in thickness. According to the large pediatric uveal melanoma study from the United States, the mean tumor size was 10 mm and thickness was 5 mm, similar to our case.7 In that study, metastatic disease at 20 years was 20% for children compared to 36% for all ages.7
In the study from Finland on pediatric uveal melanoma, the ratio of girls to boys was 2 to 1 and metastasis was 24% at 10 years. They found no association between mortality rates and tumor size; however, by statistical analysis, mortality was related to higher tumor stage (size and location), age older than 17 years, female sex, and ciliary body location.3 In a matched-cohort study from the United States on 122 children (> 20 years) with uveal melanoma compared with mid-adults (21 to 60 years) and older adults (> 60 years), Kaplan–Meier estimates of metastasis for posterior uveal melanoma at 3, 5, and 10 years was 2%, 11%, and 18% for children, 9%, 14%, and 21% for mid-adults, and 9%, 34%, 33% for older adults, respectively.4 They concluded that children with posterior uveal melanoma manifested a lower rate of metastasis compared to mid-adults and older adults.4
When confirming the diagnosis of uveal melanoma, congenital predisposing conditions should come to mind. Predisposing factors include neurofibromatosis type 1, ocular or oculodermal melanocytosis, dysplastic nevus syndrome, and germline mutation of BRCA1-associated protein 1 (BAP1). Neurofibromatosis can promote a risk for cutaneous tumors, central nervous system tumors, and cutaneous/ocular melanoma. Ocular melanocytosis is noted in 3% of patients with uveal melanoma.8 There is a suggestion that uveal melanoma occurs earlier in patients with melanocytosis at a mean age of 58 years.8 However, those with uveal melanoma arising from ocular melanocytosis have double the risk for metastasis compared to those without melanocytosis.8
There is increasing evidence for a uveal melanoma cancer syndrome with BAP1 germline mutation. Preliminary small case series have shown that BAP1 is a tumor suppressor gene located on chromosome 3p21. Mutation can lead to several cancers, including malignant mesothelioma, uveal melanoma, cutaneous melanoma, and cutaneous atypical intradermal tumors (P ≤ .001).9 For young patients with uveal melanoma, we generally test for BAP1 germline defect. In our case, there was no neurofibromatosis, melanocytosis, dysplastic nevus syndrome, familial uveal melanoma, or family history of cutaneous melanoma or BAP1-related cancers. There is further evidence that BAP1 mutation could explain the rare familial occurrence of melanoma.
The selected treatments for uveal melanoma depend on tumor size, location, age, and other factors. Plaque brachytherapy is the most commonly used therapy, offering local tumor control in approximately 98% of cases. In our 13-year-old patient, a custom-designed episcleral radioactive plaque was employed. Long-term follow-up will be necessary for monitoring systemic metastasis.
Uveal melanoma in children is rare, but can occur. It should be suspected in any child with a melanocytic intraocular tumor. Melanoma in children shows slightly fewer clinical features and better prognosis compared to melanoma in adults. This could be partly due to a more robust immune system and possibly fewer genetic alterations.