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This report relates to a retrospective analysis of two non-randomised cohorts of patients with pineoblastoma, with some differences in presenting features and treatment characteristics. We have identified a large difference in survival depending on the possession or otherwise of the mutated RB (retinoblastoma) gene in the genome/karyotype. Eight children with familial retinoblastoma (non-metastatic at presentation) developed pineoblastoma and were treated by chemotherapy and radiotherapy. The survival of these patients was compared with the survival of nine non-metastatic sporadic cases of pineoblastoma similarly staged and treated. One out of eight children having the RB mutation in the genome survived compared with seven out of nine in the group with sporadic pineoblastoma (P = 0.002). It is suggested that the inheritance of the mutated retinoblastoma gene is not only causal in the generation of this tumour type but, in a way that is yet to be defined, renders such tumours more aggressive or less responsive to therapy. With the current interest in the role of RB mutations in other cancers (where the prognostic import of single genes is less easily identified), this observation may have wider relevance.

The RB1 gene mutation was investigated in a child with ectopic intracranial retinoblastoma using DNA obtained from both the pineal and retinal tumours of the patient. A nonsense mutation in exon 17 (codon 556) of the RB1 gene was found to be present homozygously in both the retinal and the pineal tumours. The same mutation was present heterozygously in the DNA from the constitutional cells of the patient, proving it to be of germline origin. The initial mutation was shown to have occurred in the paternally derived RB1 allele. The mutation is in an area of the gene that encodes the protein-binding region known as the 'pocket' region and has been detected in other cases of retinoblastoma.

The results of treatment with platinum based combination chemotherapy in ten patients with intracranial germ cell tumours (GCT) are presented. Two patients, treated for relapse within the central nervous system (CNS), attained partial responses of short duration. One patient with systemic relapse was successfully salvaged with chemotherapy. Seven patients received primary chemotherapy, six of whom received a 'CNS friendly' regimen consisting of vincristine, etoposide, carboplatin (VEJ) prior to craniospinal axis (CSA) irradiation. Three complete and three partial responses, and one patient with stable disease, were seen prior to irradiation. All seven patients are alive and remain disease-free at a median time of 12 months after treatment. Current treatment policy for germinomas attaining complete response to two courses of VEJ is a lowered CSA dose prescription, while non-germinomatous germ cell tumours (NGGCT) receive standard total dose CSA irradiation.

Radioiodinated metaiodobenzylguanidine (MIBG) has been used for diagnostic purposes to image neural crest tumors. We report the uptake of 123I MIBG in a child with ectopic intracranial retinoblastoma. It is felt that 123I MIBG scintigraphy may have a role in detecting occult metastatic disease in these patients.

Twelve out of a series of 630 children with retinoblastoma, treated in the ocular oncology units at St Bartholomew's and Moorfields Eye Hospitals during the past 30 years, have developed ectopic intracranial retinoblastoma. The ectopic tumour occurred in the pineal region in eight children and in the suprasellar region in four. Ten patients had bilateral retinoblastoma, one unilateral disease, and one child presented with an isolated suprasellar tumour but no evidence of retinal disease. The interval from the initial diagnosis of retinoblastoma to the development of ectopic intracranial disease ranged from 4 to 70 months, median 34 months. Methods of treatment for the ectopic tumour varied, but all 12 children died with a median survival of only 8 months following the diagnosis of ectopic retinoblastoma. Subsequent spread of tumour to other sites within the central nervous system proved to be the most frequent cause of death. Ectopic intracranial retinoblastoma is a potentially curable neoplasm, but it requires adequate therapy to the whole neuraxis as well as high dose equivalent radiotherapy to the primary tumour.

A 13-year-old boy developed widespread osteoblastic bone metastases, with dissemination throughout the neuraxis, 1 year following treatment of a differentiated (Kernohan and Sayre grade II) astrocytoma of the left parietal cortex. This unusual clinical picture and the possible route of tumour dissemination are discussed.