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.