Likelihood of germline mutation with solitary retinoblastoma based on tumour location at presentation

Background/aimsTo evaluate the likelihood of germline mutation in patients presenting with solitary retinoblastoma based on tumour location at first examination. MethodsRetrospective analysis of solitary unilateral retinoblastoma for likelihood of germline mutation (family history of retinoblastoma and/or genetic testing indicating germline RB1 mutation and/or development of additional new or bilateral tumours) based on tumur location at presentation (macular vs extramacular). ResultsOf 480 consecutive patients with solitary retinoblastoma, 85 were in the macula (18%) and 395 were extramacular (82%). By comparison (macular vs extramacular tumours), macular tumours had smaller basal diameter (12.7 mm vs 18.9 mm, p<0.001) and smaller tumour thickness (6.1 mm vs 10.7 mm, p<0.001). Patients with macular tumours demonstrated greater likelihood for germline mutation (23% vs 12%, OR=2.18, p=0.011), specifically based on family history of retinoblastoma (13% vs 2%, OR=4.64, p=0.004), genetic testing showing germline RB1 mutation (27% vs 15%, OR=2.04 (95% CI 1.04 to 4.01), p=0.039), development of new tumours (13% vs 3%, OR=5.16 (95% CI 2.06 to 12.87), p=0.001) and/or development of bilateral disease (9% vs 2%, OR=4.98 (95% CI 1.70 to 14.65), p=0.004). ConclusionsAmong patients with solitary unilateral retinoblastoma, those presenting with macular tumour (compared with extramacular tumour) show 2.18 times greater likelihood for germline mutation and an even higher likelihood of development of subsequent tumours. Solitary macular retinoblastoma should raise an index of suspicion for likely germline mutation and multifocal disease.