Molecular and clinicopathological characteristics of NTRK fusions in papillary thyroid carcinoma: Hospital experience with a literature review.

Neurotrophic tyrosine receptor kinase (NTRK) fusions are rare but significant oncogenic drivers in papillary thyroid carcinoma (PTC). This study aims to delineate the clinicopathological and molecular characteristics of NTRK PTC and situate these findings within the current literature to advance diagnostic accuracy. Retrospective analysis of targeted next-generation sequencing (NGS) data from 66 primary thyroid cancer patients identified two female cases with NTRK fusions: a 22-year-old with TPR::NTRK1 and a 53-year-old with ETV6::NTRK3, both validated by fluorescence in situ hybridization (FISH). The TPR::NTRK1 patient presented with multifocal left-sided PTC, exhibiting lymph node metastasis (22/45), capsular invasion, multiple pulmonary nodules, and positive pan-TRK immunohistochemistry (IHC). Histologically, the tumor showed papillary architecture with invasive growth. The 12-month follow-up after total thyroidectomy, neck dissection, and radioactive iodine therapy (131I) showed no PTC recurrence and revealed calcified proliferative changes in the pulmonary nodules. The ETV6::NTRK3 patient had a unifocal right-sided encapsulated PTC with no evidence of metastasis and negative pan-TRK IHC. Histology revealed a predominant follicular architecture with focal conventional papillary features. Following right hemithyroidectomy, no recurrence or metastasis was observed at the 24-month follow-up. This study highlights the importance of targeted NGS combined with FISH and clinicopathological analysis for accurate diagnosis in NTRK fusion PTC. While pan-TRK IHC is useful for initial screening, confirmatory NGS is essential to avoid false-negative results.