Clinical features distinguish childhood chordoma associated with tuberous sclerosis complex (TSC) from chordoma in the general paediatric population

Abstract

Background: Chordoma, an age-dependent rare cancer, arises from notochordal remnants. Fewer than 5% of chordomas occur in children. Tuberous sclerosis complex (TSC) is an autosomal dominant neurocutaneous syndrome characterised by abnormal tissue growths in multiple organ systems. Reports of chordoma in children with TSC suggest that TSC1 and TSC2 mutations may contribute to chordoma aetiology.

Methods: To determine whether the 10 TSC-associated childhood chordomas reported in the literature are representative of chordoma in the general paediatric population, the authors compared age at diagnosis, primary site and outcome in them with results from a systematic assessment of 65 paediatric chordoma cases reported to the US population-based cancer registries contributing to the SEER Program of the National Cancer Institute.

Results: TSC-associated paediatric chordomas differed from chordomas in the general paediatric population: median age at diagnosis (6.2 months, TSC, vs 12.5 years, SEER); anatomical site (40% sacral, TSC, vs 9.4% sacral, SEER); and site-specific age at diagnosis (all four sacral chordomas diagnosed during the fetal or neonatal period, TSC, vs all six sacral chordomas diagnosed at >15 years, SEER). Finally, three of four patients with TSC-associated sacral chordoma were alive and tumour-free at 2.2, 8 and 19 years after diagnosis versus a median survival of 36 months among paediatric patients with sacral chordoma in SEER.

Conclusions: These results strengthen the association between paediatric chordoma and TSC. Future clinical and molecular studies documenting the magnitude and clinical spectrum of the joint occurrence of these two diseases should provide the basis for delineating the biological relationship between them.

Figure 1. Distribution of primary chordoma sites by age in SEER

Each site-by-age segment is depicted as a proportion of all chordomas in the pediatric age group. The frequency of chordoma overall increases with age. In this study population, chordoma site appears to be age dependent. While chordoma was diagnosed at intracranial sites in all age groups, chordoma of the mobile spine appeared in the second tertile, and sacral chordoma was diagnosed only in adolescents (third tertile).

Figure 2. Survival of pediatric chordoma by primary site in SEER

Kaplan-Meier plot of cause-specific survival of patients aged 0 – 18 years diagnosed with chordoma affecting intracranial sites, the mobile spine, or the sacrum and reported to SEER. Median follow-up for the entire cohort was 48.5 months. Median survival was 36 months for patients with sacral chordoma. The median survival has not been reached for chordoma at other sites.