Cytomorphologic features of NTRK-rearranged thyroid carcinoma

NTRK-rearranged thyroid carcinomas (NRTC), though rare, harbor a potential therapeutic target. The cytomorphologic features by fine needle aspiration (FNA) and the utility of preoperative molecular testing for NRTC remain largely uncharacterized. We provide a detailed cytomorphologic analysis of an institutional NRTC cohort with clinical, radiologic, histopathologic, and molecular correlations.

Our NRTC FNA cohort included 21 specimens from 19 patients. The mean age and female-to-male ratio were 42 years and 2.2:1, respectively. Predominantly alcohol-stained Papanicolaou smears and liquid-based preparations were reviewed for 14 patients with available materials, and histologic review of subsequent resections was conducted for all 19 patients. Imaging and clinical data were accessed through electronic medical records.

Sonographically, NRTC were hypoechoic (87%), predominantly solid (53%) with limited central vascularity (27%), ill-defined borders (67%), and microcalcifications (67%). Observed cytomorphologic features include mixed architectural patterns (79%), fibrosis (93%), oncocytic and vacuolated cytoplasm (36% and 43%, respectively), and abundant intranuclear pseudoinclusions (14%). Most NRTC FNAs were classified as suspicious for malignancy or malignant (89%). One case classified as atypia of uncertain significance underwent ThyroSeq sequencing where a NTRK1 fusion was identified.

Although NRTC did not show a consistent cytomorphologic signature, mixed architectural patterns, prominent fibrosis and distinct cytoplasmic or nuclear features should raise suspicion for NRTC and, when accompanied by negative BRAFV600E by immunohistochemistry on cell block material, aid in selecting cases for molecular testing. This algorithmic approach may help identify potential NRTC, maximizing treatment options for patients, especially in patients for whom treatment planning is complicated.