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.