Thyroid carcinoma metastases to central nervous system and vertebrae

Introduction: Metastatic thyroid carcinoma rarely involves the parenchyma of the central nervous system (CNS) or vertebral bones. While various mutations have been identified in primary thyroid carcinomas and differ based on the histological type, little is known about the molecular features of thyroid carcinoma metastases to brain or spinal column. Based on limited prior literature, we hypothesized that TERT mutations might be enriched in CNS metastatic lesions. Material and methods: CNS/vertebral metastases were identified via database search, 1.01.2006 to 9.08.2021, and muta-tion/fusion testing performed. Results: 21 surgically resected lesions were identified from 16 patients: 15/21 metastases were to the vertebral bone, requiring neurosurgical intervention for cord compression and 6/21 metastases were intraparenchymal. Male : female ratio was 1 : 1, with median age at the time of CNS metastasis of 62 years. Metastases were of varied histological types, with follicular the most common; the histological subtype often matched in patients with multiple CNS metastases although 2 patients showed dedifferentiation in subsequent metastases. Diagnosis of thyroid carcinoma antedated development of CNS metastases in all but 2 patients in whom a surgically-resected bone metastasis represented their first diagnosis. Intervals for the remaining 14 patients from primary to CNS/vertebral metastasis ranged from 6 months to 41 years. Muta-tions were multiple in 14/15 cases, including TERT (n = 12) and NRAS (n = 9), with fewer TP53, ATM, AKT1, PTEN, NOTCH1 mutations. Two specimens had fusions involving RET. Conclusions: TERT mutation occurred in a significantly higher percentage (80%) of mutations than reported for primary tumors, underscoring the need for molecular testing of the metastases, should a targeted therapy become available.