PATH-38. Rare co-occurrence of a clival chordoma and Tetralogy of Fallot in a pediatric patient: A role for T-Box transcription factors?

Abstract Chordomas are rare slow-growing malignant bone tumors of notochord origin, with incidence of 0.08 per 100,000/year and median 5-year survival of 67%. Fewer than 5% occur before age 20. Most pediatric chordomas arise from the skull-base. Tetralogy of Fallot, a heterogeneous congenital cyanotic heart disease comprised of a ventricular septal defect, overriding aorta, pulmonary stenosis, and right ventricular hypertrophy, is also a rare disease, with incidence of approximately 1 in 2,000 live births. Here we describe a girl with Tetralogy of Fallot who at age 10 years presented with 3 months of dysarthria, difficulty swallowing, morning headaches, and tongue paresthesia and fasciculations. Brain MRI showed a clival chordoma infiltrating into the pons and medulla. The tumor was partially resected. Pathology of the tumor showed cords and nests of epithelioid cells in a chondromyxoid background, expressing brachyury, cytokeratin (CK AE1/AE3), and S100 and no DNA sequence variants or RNA gene fusions of clinical significance by Onco-Kids somatic panel. Patient received 73.5 Gy to the clivus with IMRT (brainstem dose of 62 Gy to 0.03 cc), with the partially-resected tumor remaining stable, now 4 years following diagnosis. To date, this is the first description of these two rare conditions, chordoma and Tetralogy of Fallot, occurring in the same patient. Interestingly, both clival chordoma and Tetralogy of Fallot are associated with the T-box gene family of developmental transcription factors: Brachyury (TBXT) is expressed in chordomas and alterations in TBX1, TBX5 and TBX20 can contribute to Tetralogy of Fallot. While random co-occurrence is not impossible (likelihood of approximately 1 in 2.08 ×109), presentation of this rare skull-based tumor of embryological origin within the context of dysregulated cardiac development suggests the intriguing possibility of a yet-unknown biological connection between the two conditions, potentially via connection of T-box developmental transcription factors.