Trilateral Retinoblastoma

The term trilateral retinoblastoma (TRb) classically refers to the association of heritable intraocular retinoblastoma with a midline brain tumor with a similar histopathology as the intraocular tumors. About 80% of cases arise in the pineal gland, which is referred to as pineal TRb. In the rest of the cases, the intracranial tumor develops in the supra- or parasellar region or rarely in the third or fourth ventricle. These cases are referred to as non-pineal TRb. The overall incidence of TRb is approximately 1.7% of all patients with Rb, up to 3.8% for patients with bilateral retinoblastoma, and 3.5% for patients with heritable retinoblastoma. The median age at diagnosis of TRb is 26 months, with a range of 1-144 months. Screening recommendations for TRb are somewhat controversial, mainly because of the low incidence of TRb, the need for anesthesia for performing magnetic resonance imaging (MRI) in this population, the risk of false positive and false negative results, the risk that the more aggressive faster-growing brain tumors may develop into an untreatable tumor within the interval between scans, the potential associated anxiety that comes with a screening program, and the uncertainty of the effectiveness of a screening program. There is no discussion about baseline brain screening with MRI, which should be performed in all Rb patients at the time of diagnosis, as well as at the time an ocular MRI under anesthesia is performed anyway. This MRI will diagnose most cases of non-pineal TRb and some cases of pineal TRb. Unfortunately, most cases with pineal TRb seem to develop after Rb, especially when Rb is diagnosed at a young age (<12 months), for whom baseline brain screening is usually too early. Almost all asymptomatic pineal TRbs are diagnosed before the age of 40 months. A modeled screening program performed every six months after Rb diagnosis until the age of 36 months will require over 300 MRIs to diagnose one pineal TRb and even more to save one life. The burden of such a screening program might be higher than the potential benefit of catching a TRb in an early stadium. However, as in most TRb cases (79%), Rb is diagnosed before the age of 12 months, and in those patients, only 11% of pineal TRb cases will be detected on baseline brain screening, one or more optimally timed MRI scans can increase the detection of asymptomatic and potentially treatable pineal TRB from 11% to 53% or higher depending on the number of MRI scans. The prognosis for pineal TRb remains poor even with aggressive treatment, as patients often die of disseminated neuraxis disease within the first year after diagnosis. Only when the tumor is detected in an early stage (<15 mm) and treated properly do patients have about a 50% chance to survive. Non-pineal TRb has a better prognosis with an overall survival chance of over 50% since 1995, irrespective of the stage it is diagnosed at. This increase can be attributed to early screening and detection of improved chemotherapy regimens, especially the use of high-dose chemotherapy with stem-cell rescue and surgical resection in certain cases if the intracranial disease is not disseminated.