Andrew Budning

Retinoblastoma CSF Metastasis Cured By Multimodality Chemotherapy Without Radiation

Objective: Cerebrospinal fluid (CSF) metastasis is the most difficult type of retinoblastoma metastasis to cure, even with bone marrow transplant. Most metastatic retinoblastoma cells express P-glycoprotein causing multidrug resistance (MDR). P-glycoprotein-rich blood vessels form blood-brain and blood-eye barriers, inhibit drug entry into central nervous system (CNS) and eyes. High-dose craniospinal radiation is too morbid for treatment of young children. To cure CSF metastasis without radiation, we designed an intensive multimodality chemotherapy regimen. Method: After left eye enucleation, a 4-month-old boy with bilateral International Intraocular Retinoblastoma Classification Group E eyes and CSF metastasis was treated with 7-cycle high-dose carboplatin and etoposide, standard-dose vincristine, and high-dose/short-infusion cyclosporine to inhibit P-glycoprotein. Intraventricular drugs, non-substrate of P-glycoprotein (cytarabine), or less susceptible to MDR (topotecan), contributed to treatment of the metastasis. On achieving complete response, he was consolidated with supralethal-dosage carboplatin, etoposide, and cyclophosphamide, and his bone marrow rescued with autologous cord blood stem cells. Results: Following 1-cycle systemic chemotherapy and 2-dose intraventricular chemotherapy, the CSF metastasis cleared. The right eye tumor regressed completely. The patient remains in remission 8.3 years after diagnosis and 7.8 years post-transplant. Conclusion: Intensive multimodality chemotherapy can cure CSF metastasis in retinoblastoma without incurring extreme morbidity from craniospinal radiation.

Toxocariasis mimicking liver, lung, and spinal cord metastases from retinoblastoma.

A boy with bilateral retinoblastoma underwent metastatic surveillance for increased risk of systemic and central nervous system metastasis because of the extensive choroid and optic nerve invasion in his enucleated eye. Two years after finishing chemotherapy, surveillance MRI showed multiple new liver, lung and spinal cord lesions. High Toxocara antibody titers, eosinophilia, and elevated IgE levels supported a diagnosis of toxocariasis, rather than retinoblastoma metastasis. This is the first report of early, asymptomatic spinal cord toxocariasis diagnosed incidentally through metastatic surveillance.

Trilateral retinoblastoma with pituitary-hypothalamic dysfunction.

Trilateral retinoblastoma is characterized by retinal tumors in one or both eyes, as well as tumors of the pineal gland or parasellar region of the brain. Here we describe a 4-month-old girl, presenting with pituitary dysfunction, hypothalamic overgrowth syndrome and central blindness, in addition to suprasellar and bilateral retinal tumors. Biopsy of the suprasellar tumor confirmed the diagnosis of trilateral retinoblastoma. After biopsy, cerebrospinal fluid (CSF) metastasis was discovered. Overgrowth persisted, but blindness and pituitary dysfunction resolved when the suprasellar tumor and CSF metastasis responded to cyclosporine-modulated systemic chemotherapy with intraventricular chemotherapy, consolidated with marrow-ablative chemotherapy and stem cell rescue of the bone marrow. Twenty months after diagnosis and 12 months after transplant, an unusual pattern of tumor recurrence was observed along the catheter of the Ommaya reservoir used for delivering intraventricular chemotherapy, which was also at the site of the previous suprasellar needle biopsy. Salvage therapy consisted of resection, stereotactic radiation, and further systemic and intraventricular chemotherapy. At 25 months after diagnosis, the patient was developing well and seeing better. However, she died 32 months after diagnosis despite the salvage therapy. This case highlights the possibility of tumor dissemination after needle biopsy of a suprasellar tumor. Biopsy may be avoided if a characteristic clinicoradiological picture of trilateral retinoblastoma is recognized. We recommend that if a pineal or suprasellar tumor is observed in a child, the eyes should be examined for retinoblastoma, thereby avoiding biopsies of the intracranial tumor, which may track difficult-to-treat tumor cells through the brain, and disseminate tumor cells into the CSF.

Bilateral idiopathic Brown's syndrome with delayed onset in the second eye.

PURPOSE We describe 6 cases of a previously unreported variation of bilateral Browns syndrome that presented in congenital form in one eye and developed later in the fellow eye with no underlying cause. METHODS We reviewed the clinical records of 6 patients from 6 separate practices to determine whether there were any common clinical features on presentation or in their clinical courses. RESULTS All 6 patients were diagnosed with unilateral congenital Browns syndrome at the first ophthalmologic assessment but showed no evidence of the syndrome in the fellow eye. In 5 cases the contralateral syndrome developed in the second eye after surgery was performed on the first eye, and in 1 case it developed before any surgery was done. The ages at onset of the syndrome in the second eye ranged from 2 to 8 years. None of the children had any evidence of systemic illness or local orbital disease to explain an acquired Browns syndrome. CONCLUSION To our knowledge, this is the first reported series of cases of bilateral Browns syndrome that manifested sequentially in the eyes with no known causes for an acquired syndrome in the second eye. This finding supports the premise that congenital and acquired Browns syndrome are on a continuum with a common pathophysiology of restriction of free movement of the superior oblique tendon in the trochlea.