Trilateral retinoblastoma (TRb) presents a management challenge, since intracranial tumours are seldom times resectable and quickly disseminate. However, there are no risk factors to predict the final outcome in each patient.
Objective To evaluate minimal disseminated disease (MDD) in the bone marrow (BM) and the cerebrospinal fluid (CSF) at diagnosis and during follow-up and reviewing its potential impact in the outcome of patients with TRb.
Methods and analysis We evaluated MDD in five patients with TRb, detecting the mRNA of CRX and/or GD2, in samples from BM and CSF, obtained at diagnosis, follow-up and relapse.
Results Treatment involved intensive systemic chemotherapy in four patients, one did not receive this treatment and died of progression of the disease. Two patients underwent stem cell rescue. Three patients had leptomeningeal relapse and died. One patient remains disease-free for 84 months. RB1 mutations were identified in the five patients, all of them were null mutations. At diagnosis, one patient had tumour cells in the CSF, and none had the BM involved. Only one case of four presented MDD during follow-up in the CSF, without concomitant detection in the BM. On leptomeningeal relapse, no case had MDD in the BM. In all these cases, cells in the CSF were positive for GD2 and/or CRX.
Conclusion CSF dissemination always concluded in the death of the patient, without concomitant systemic dissemination denoting the importance of increasing treatment directed to the CSF compartment. The MDD presence could indicate a forthcoming relapse.
- intracranial tumor
- leptomeningeal dissemination
- bone marrow
- neuroblastic tumor
- RB1 gene
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Presented at Preliminary results of this work were presented at the annual meeting of Argentinian Society of Clinical Investigation (SAIC) 2017, Buenos Aires, Argentina.
Contributors AVT and GLC conceived and designed the study. AVT and VEL developed and validated the molecular biology technique. AVT, VEL, RA, JR and IS processed the samples. CS and DFA participated in subject enrolment and sample collection. SI and CS drafted the work and revising it critically for important intellectual content. AVT, DFA and GLC designed the study and wrote the paper. All authors contributed to the review of the literature, in drafting the manuscript and in approving the final manuscript.
Funding This study was supported by the Fund for Ophthalmic Knowledge, the Natalí Dafne Flexer Foundation (Argentina) and Grants from the National Agency of Scientific and Technological Promotion from Argentina (Grant numbers: PICT 2015-1820 and BID-PID 129 PAE 37.011). No conflicting relationship exists for any of the authors.
Competing interests None declared.
Patient consent Guardian consent obtained.
Ethics approval Research Coordination Board of Pediatric Hospital ‘Prof. Dr. Juan P. Garrahan’ (approval number: 751)
Provenance and peer review Not commissioned; externally peer reviewed.
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