Asynchronous pineoblastoma is more likely after early diagnosis of retinoblastoma: a meta-analysis

Abstract

Purpose: To determine the risk of patients with an early diagnosis of heritable retinoblastoma being diagnosed with TRb (or pineoblastoma) asynchronously in a later stage and its effect on screening.

Methods: We updated the search (PubMed and Embase) for published literature as performed by our research group in 2014 and 2019. Trilateral retinoblastoma (TRb) patients were eligible for inclusion if identifiable as unique and the age at which TRb was diagnosed was available. The search yielded 97 new studies. Three new studies and eight new patients were included. Combined with 189 patients from the previous meta-analysis, the database included 197 patients. The main outcome was the percentage of asynchronous TRb in patients diagnosed before and after preset age thresholds of 6 and 12 months of age at retinoblastoma diagnosis.

Results: Seventy-nine per cent of patients with pineoblastoma are diagnosed with retinoblastoma before the age of 12 months. However, baseline MRI screening at time of retinoblastoma diagnosis fails to detect the later diagnosed pineal TRb in 89% of patients. We modelled that an additional MRI performed at the age of 29 months picks up 53% of pineoblastomas in an asymptomatic phase. The detection rate increased to 72%, 87% and 92%, respectively, with 2, 3 and 4 additional MRIs.

Conclusions: An MRI of the brain in heritable retinoblastoma before the age of 12 months misses most pineoblastomas, while retinoblastomas are diagnosed most often before the age of 12 months. Optimally timed additional MRI scans of the brain can increase the asymptomatic detection rate of pineoblastoma.

Keywords: MRI; PNET; magnetic resonance imaging; pineal gland; pineoblastoma; retinoblastoma; trilateral retinoblastoma.

Fig. 1

Magnetic resonance images (MRI) of Case 1. A 3.5‐month‐old child presented with bilateral retinoblastoma (cT2a and cT1a by 8th edition TNM) (Mallipatna et al. 2017). Baseline MRI performed on the day of diagnosis of bilateral retinoblastoma. Note a large (cT2a) tumour (14 × 14 × 9 mm) in the right eye (A, T2‐weighted image), while the tumours in the left eye were small (cT1a) and not visible. The midline brain MRI showed a normal 5 × 4 mm pineal gland (B and C, between arrowheads, T1‐weighted non‐contrast‐enhanced images) and no suprasellar mass. The right eye was enucleated and revealed no high‐risk histopathologic features (Sastre et al. 2009). Tumours in the left eye were controlled focally with OCT‐guided laser (Soliman et al. 2017b, 2018). Systemic chemotherapy was not required. The child was examined under anaesthesia (EUA) every 3–4 weeks for 8 months, when the follow‐up intervals were extended to 6 weeks for 6 months then to 8 weeks for 6 months. Twenty months from diagnosis at the age of 23 months, the routine EUA was postponed because of recent vomiting, suspected to be related to a viral infection. Intermittent vomiting persisted despite medical therapy, and after 10 days, the child was found unconscious and brought to emergency care. An urgent MRI of the brain revealed a large pineoblastoma showed a large enhancing pineal mass (37 × 30 × 26 mm) (D and E, arrow, T1‐weighted contrast‐enhanced images) invading the midbrain tectum and tegmentum anteriorly, the superior cerebellum posteriorly, and extending into the aqueduct and the third ventricle superiorly, resulting in acute triventricular hydrocephalus. Tumour deposits cranially cover the cerebellum (E, arrowhead). Multiple nodular drop metastases cover the brainstem, and numerous enhancing nodular metastases were observed along the spinal cord and cauda equina nerve roots (F and G, arrows, T1‐weighted contrast‐enhanced images). The child died two days later.

Fig. 2

Number of cases with synchronous versus asynchronous (true and surrogate) asymptomatic pineoblastoma by age at diagnosis of retinoblastoma.