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Updated: Dec 5, 2025
Spontaneous Murine Model of Anaplastic Thyroid Cancer
Published on: February 3, 2023
Cytomorphologic features of NTRK-rearranged thyroid carcinoma
Kartik Viswanathan1, Ying-Hsia Chu2, William C Faquin1
1Departments of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
Background:
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.
Methods:
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.
Results:
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.
Conclusion:
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.
Insights
NTRK-rearranged thyroid carcinomas (NRTC) have potential therapeutic targets. Cytomorphologic analysis of fine needle aspiration (FNA) and molecular testing can help identify these rare cancers for better treatment planning.
Area of Science:
- Oncology
- Cytopathology
- Molecular Diagnostics
Background:
- NTRK-rearranged thyroid carcinomas (NRTC) are rare but therapeutically targetable.
- Cytomorphologic features of NRTC via fine needle aspiration (FNA) and preoperative molecular testing are not well-characterized.
Purpose of the Study:
- To analyze cytomorphologic features of NRTC using FNA.
- To correlate FNA findings with clinical, radiologic, histopathologic, and molecular data.
- To evaluate the utility of preoperative molecular testing for NRTC.
Main Methods:
- Retrospective review of 21 NRTC FNA specimens from 19 patients.
- Analysis of cytomorphologic features on Papanicolaou and liquid-based cytology preparations.
- Histopathologic review of resections for all patients.
- Correlation with clinical, imaging, and molecular data.
Main Results:
- Sonographic findings included hypoechogenicity, solid composition, ill-defined borders, and microcalcifications.
- Cytomorphologic features observed: mixed architectural patterns, fibrosis, oncocytic/vacuolated cytoplasm, and intranuclear pseudoinclusions.
- Most FNAs were classified as suspicious or malignant (89%); one case with atypia revealed an NTRK1 fusion via molecular testing.
Conclusions:
- NRTC lacks a consistent cytomorphologic signature but specific features (mixed patterns, fibrosis, cytoplasmic/nuclear characteristics) warrant suspicion.
- Combining cytomorphology with negative BRAFV600E immunohistochemistry can guide selection for molecular testing.
- An algorithmic approach aids in identifying NRTC, optimizing treatment strategies for patients.
