Diagnosis and Management of Retinoblastoma

Carol L. Shields, MD; Jerry A. Shields, MD


Cancer Control. 2004;11(5) 

In This Article

Life-Threatening Problems

Children with retinoblastoma are at risk for three important, life-threatening problems including metastasis from retinoblastoma, intracranial neuroblastic malignancy (trilateral retinoblastoma), and second primary tumors.

At Risk for Metastasis

Retinoblastoma metastasis, when it occurs, generally develops within 1 year of the diagnosis of the intraocular tumor. Those at greatest risk for metastasis show features of retinoblastoma invasion beyond the lamina cribrosa in the optic nerve, in the choroid (>2 mm dimension), sclera, orbit, or anterior chamber.[13] Eyes with invasion of the optic nerve or choroid generally demonstrate large retinoblastoma over 15 mm greatest dimension along with elevated intraocular pressure and total retinal detachment.[14,15] Patients with evidence of invasive retinoblastoma should be treated with chemotherapy for 4 to 6 months to prevent metastases; however, criteria for regarding the need for adjuvant chemotherapy remain unclear. In an analysis from our department, metastases were reduced from 24% in those without preventive chemotherapy to 4% in those with chemotherapy.[13]

At Risk for Neuroblastic Intracranial Malignancy (Trilateral Retinoblastoma)

There is an association of neuroblastic intracranial malignancy in patients with the hereditary form of retinoblastoma, most often manifesting as pineoblastoma or other parasellar tumors.[16] The pineoblastoma is identical to retinoblastoma from an embryologic and pathologic standpoint.[16,17,18,19] This association of midline intracranial pineal tumors and suprasellar/parasellar neuroblastic tumors with bilateral retinoblastoma has been termed trilateral retinoblastoma.[20] Loss of function of the retinoblastoma gene is believed to confer an increased susceptibility to developing these intracranial tumors. Trilateral retinoblastoma is found in approximately 3% of all children with retinoblastoma.[18,19] Those patients with bilateral or familial disease are at greatest risk, with 5% to 15% developing this finding.[18,19] Hence, patients with bilateral or familial retinoblastoma are advised to have screening for pineoblastoma using computed tomography or magnetic resonance imaging of the brain twice yearly for the first 5 years of life. In some cases, the intracranial tumor preceded the diagnosis of retinoblastoma.[18] It is possible that many cases of pineoblastoma were previously misinterpreted as metastatic retinoblastoma to the brain. Unlike other second tumors, the pineoblastoma usually occurs during the first 5 years of life,[19] whereas second tumors often take many decades to develop. Unfortunately, pineoblastoma is usually fatal. The possibility of pineoblastoma should be included in the genetic counseling of patients with hereditary retinoblastoma. Newer evidence suggests that recent treatment methods of systemic chemoreduction for retinoblastoma may prevent trilateral retinoblastoma.[21] In a study of 100 patients with hereditary retinoblastoma, trilateral retinoblastoma was found in no patient who received chemoreduction and it would have been expected in 5 to 15 patients. Thus, prevention of trilateral retinoblastoma may be possible with neoadjuvant chemotherapy.

At Risk for Second Primary Tumors

Another important aspect of genetic counseling concerns the development of new genetically related cancers in survivors of bilateral or heritable retinoblastoma. It is now recognized that a child with retinoblastoma has approximately a 5% chance of developing another malignancy during the first 10 years of follow-up, 18% during the first 20 years, and 26% within 30 years.[22] The 30-year cumulative incidence is approximately 35% or even higher for those patients who received radiation therapy (external beam therapy) compared with an incidence rate of 6% for those patients who avoided radiation. Therefore, patients with bilateral retinoblastoma have an increased incidence of second tumors, and this rate is further increased in those treated with external radiation therapy.[22] Osteogenic sarcoma, often involving the femur, is most common, but other tumors such as spindle cell sarcoma, chondrosarcoma, rhabdomyosarcoma, neuroblastoma, glioma, leukemia, sebaceous cell carcinoma, squamous cell carcinoma, and malignant melanoma have also been recognized. The mean latency period for the appearance of the second primary is approximately 13 years.[22] Patients who survive a second tumor are at risk for a third, fourth, and even fifth nonocular tumor.[23]


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