Fine-needle aspiration cytomorphology of papillary thyroid carcinoma with NTRK gene rearrangement from a case series with predominantly indeterminate cytology.

ABSTRACT

BACKGROUND: Neurotrophic tyrosine kinase receptor (NTRK) rearrangement has been reported in a subset of papillary thyroid carcinoma (PTC) cases. Little is known about the cytomorphologic features of NTRK-rearranged PTC. METHODS: We report an institutional series of 13 fine-needle aspiration (FNA) specimens of NTRK-rearranged PTC with a predominantly indeterminate cytology diagnosis. NTRK3 or NTRK1 rearrangements were detected on FNA or surgical specimens by next-generation sequencing. RESULTS: The 13 patients had a median age of 18 years; 10 patients were female and 3 patients were male. In 10 (77%) cases, cytology was indeterminate, and histopathologic follow-up was predominantly the follicular variant of PTC (n = 8 [62%]), mostly infiltrative subtype. Of 12 FNA specimens available for review, a predominant loosely cohesive group pattern was the most commonly encountered architectural pattern (n = 5 [41%]), followed by single cell (n = 3 [25%]), thick cord (n = 2 [17%]), and microfollicular pattern (n = 2 [17%]). Background lymphocytic thyroiditis was observed in 9 cases. At the cellular level, the cytoplasm was moderate and granular, occasionally vacuolated. Classic PTC nuclear features (eg, nuclear enlargement, elongation, grooves, and nuclear membrane irregularity) were present but were often focal and subtle. Chromatin was often granular. Intranuclear pseudoinclusions were absent or rare. CONCLUSION: Our study demonstrates that most cases of NTRK rearrangement lack classic PTC cytomorphologic characteristics. Loosely cohesive groups and single cells with granular, sometimes vacuolated cytoplasm and subtle nuclear features are often seen on FNA specimens. Recognizing these characteristics may be helpful to preoperatively prompt molecular testing, including NTRK rearrangement analysis.