Brain metastases of papillary thyroid carcinoma origin are derived from aggressive histologic variants and demonstrate similar adverse morphology in the metastatic lesion

Background: Distant metastases of papillary thyroid carcinoma are exceedingly rare. We analyzed all cases of brain metastases of papillary thyroid cancer at our institution and performed a literature review over the past ten years to identify histologic and molecular features of primary and metastatic tumors. Methods: Following institutional review board approval, the entire pathology archives at our institution were searched for cases of papillary thyroid carcinoma metastatic to brain. Patient demographics, histologic features of both primary and metastatic tumors, molecular information, and clinical outcomes were investigated. Results: We identified 8 cases of metastatic papillary thyroid carcinoma to brain. The average age at time of diagnosis of metastases was 56.3 years (range: 30-85). Average time from diagnosis of primary thyroid cancer to brain metastasis was 9.3 years (range: 0-24 years). All primary thyroid carcinomas demonstrated aggressive subtypes which were correspondingly seen in brain metastases. Next-generation sequencing revealed the most common mutations were identified in BRAFV600E, NRAS, and AKT1 with one tumor harboring a TERT promoter mutation. Six out of eight patients were deceased at the time of study with an average survival time of 2.3 years (range: 0.17-7 years) following diagnosis of brain metastasis. Conclusions: Based on our study, it is highly unlikely that a low-risk variant of papillary thyroid carcinoma will metastasize to the brain. Therefore, careful and accurate reporting of the papillary thyroid carcinoma subtype in primary thyroid tumors is warranted. Certain molecular signatures are associated with more aggressive behavior and worse patient outcomes and next-generation sequencing should be performed on metastatic lesions.