Conclusion
Germline SDHB mutations rarely occur in patients with PTC and may contribute to its aggressiveness. Somatic TERT promotor mutations rarely occur in PGL and contribute to its aggressiveness and metastatic potential.
Purpose
About 40% of paragangliomas (PGL) are due to germline mutations in one of several susceptibility genes. These genes rarely predispose to other non-PGL tumors. Here, we describe and functionally characterize a germline SDHB mutation in a patient who developed a BRAF V600E mutation-positive papillary thyroid cancer (PTC) and a TERT promotor mutation-positive PGL. Experimental design: A 28-year-old asymptomatic man was discovered incidentally to have a large left-sided mid-abdominal PGL and PTC. He underwent resection of the PGL and total thyroidectomy and neck dissection followed by I-131 adjuvant therapy for PTC. The histopathology revealed a high-grade PGL and a tall cell-variant PTC with lymph node metastases (T1b N1b M0). He soon developed PGL spinal metastases that have been rapidly progressing and is currently being treated with Lu177-dotatate therapy. Family screening revealed a positive SDHB mutation in the mother, a son, and a brother.
Results
In addition to the heterozygous SDHB germline mutation (c.688C>T, p.Arg230Cys), molecular analysis revealed a somatic TERT promotor mutation (C228T) in PGL (negative in PTC) and a somatic BRAF V600E mutation in PTC (negative in PGL). Functional studies showed a higher proliferation rate in the mutant compared with the wild-type SDHB.