Introduction
Retinoblastoma (RB) is the most common primary intraocular malignancy in pediatric patients. In most cases, it results from either a germline (hereditary) or somatic (non-hereditary) mutation of the RB1tumor suppressor gene located on chromosome 13q14.1,2,3 Hereditary retinoblastoma is associated with an increased lifetime risk of second primary malignant neoplasms (SPMNs), most of which are either pineoblastoma (ectopic intracranial retinoblastoma) or sarcomas. While RB-associated pineoblastoma tends to occur during early childhood, most RB-associated sarcomas occur years or even decades after initial retinoblastoma diagnosis and treatment. SPMNs are particularly likely to occur in patients with hereditary retinoblastoma who have nonsense mutations inRB1 .4 The reported incidence of SPMNs in the published literature varies due to differing definitions of SPMNs, differing lengths of follow-up, referral practice biases, and differences in retinoblastoma treatment.5 SPMNs are now the leading cause of death in patients with hereditary retinoblastoma in the developed world.6 Because SPMNs often occur decades following the initial diagnosis of retinoblastoma, long-term follow-up is necessary to accurately determine the frequency of and risk factors for the development of such outcomes in retinoblastoma survivors.
Herein we report the demographic and historical features of a series of patients with non-pineoblastoma SPMNs, the clinical features and treatment for the retinoblastoma in these cases, the types of SPMNs that occurred in these patients, and the treatment outcomes of these patients following SPMN diagnoses over a forty-three-year period in a single referral ocular oncology practice.