Likelihood of Germline Mutation With Solitary Unilateral Retinoblastoma Based on Patient Age at Presentation: Analysis of 482 Consecutive Patients

Abstract

Purpose: To evaluate the likelihood of germline retinoblastoma in patients presenting with solitary unilateral retinoblastoma, based on age at presentation. Methods: This retrospective case series of 482 consecutive patients presenting with solitary unilateral retinoblastoma analyzed the likelihood of germline retinoblastoma, defined as family history of retinoblastoma, germline retinoblastoma mutation documented on genetic testing, and/or development of bilateral disease and/or additional new tumors. This analysis was based on age at presentation (0 to 12 months vs older than 12 to 24 months vs older than 24 to 36 months vs older than 36 months) and a sub-study was conducted on infant age at presentation (0 to 3 months vs older than 3 to 6 months vs older than 6 to 9 months vs older than 9 to 12 months). Results: Of the overall group (482 consecutive patients) with solitary unilateral retinoblastoma, there were significantly different findings in the youngest age group (0 to 12 months old) with greater family history of retinoblastoma (10% vs 2% vs 1% vs 2%, P = .004), smaller median basal diameter (18.0 vs 20.0 vs 20.0 vs 20.0 mm, P = .014), smaller median tumor thickness (8.7 vs 10.0 vs 11.5 vs 10.0 mm, P = .002), greater macular tumor location (33% vs 16% vs 10% vs 8%, P < .001), and greatest likelihood of germline mutation (29% vs 17% vs 8% vs 9%, P = .001). By comparison, patients 1 year and younger (vs older than 1 year) demonstrated a 2.96 odds ratio (OR) ( P = .001) for likelihood of germline retinoblastoma. For those classified as infants (1 year and younger) (n = 132 consecutive patients), the youngest patients (0 to 3 months old) demonstrated the greatest likelihood for germline mutation (61% vs 20% vs 24% vs 22%, P = .009) and greatest odds ratio (5.52, P = .002) compared to patients older than 3 to 12 months. Conclusions: The youngest patients with solitary unilateral retinoblastoma showed the greatest likelihood of germline disease when evaluating all patients (1 year and younger vs older than 1 year of age) (OR = 2.96) and the substudy of infants (3 years and younger vs older than 3 to 12 months old) (OR = 5.52). [ J Pediatr Ophthalmol Strabismus . 2021;58(6):355–364.]

Primary Macular Retinoblastoma: Clinical Presentation and Treatment Outcomes

“…In our previous study of RB including all macular and nonmacular tumors, the mean age at presentation of RB was 29 months (median 24 months), 17 suggesting that macular tumors tend to present at a younger age (minimum of 12 months earlier) in eyes with an increased risk of harboring germline RB1 mutation. 18 A study by Abramson and Gombos 19 showed that posterior pole tumors have a more aggressive clinical course than peripheral tumors that present later in life. This might be attributed to 2 factors; that is, tumor location and tumor dimensions.…”

“…In our previous study of RB including all macular and nonmacular tumors, the mean age at presentation of RB was 29 months (median 24 months), 17 suggesting that macular tumors tend to present at a younger age (minimum of 12 months earlier) in eyes with an increased risk of harboring germline RB1 mutation. 18…”