Abstract
Simple SummaryAccurate diagnosis of thyroid fine-needle aspiration cytology is a significant clinical challenge. A method to detect thyroid cancer at the cellular level would be invaluable to reduce diagnostic uncertainty and improve clinical decision making. We studied the ability of confocal fluorescence polarization imaging of an exogenous fluorophore, methylene blue, to provide quantitative discrimination of cancerous cells in human samples. Our results indicate that fluorescence polarization imaging provides a reliable biomarker of thyroid cancer and holds the potential to shift the paradigm of cellular level cancer diagnosis from subjective visual assessment to objective measurement.Background: Diagnostic accuracy of the standard of care fine-needle aspiration cytology (FNAC) remains a significant problem in thyroid oncology. Therefore, a robust and accurate method for reducing uncertainty of cytopathological evaluation would be invaluable. Methods: In this double-blind study, we employed fluorescence emission and quantitative fluorescence polarization (Fpol) confocal imaging for sorting thyroid cells into benign/malignant categories. Samples were collected from malignant tumors, benign nodules, and normal thyroid epithelial tissues. Results: A total of 32 samples, including 12 from cytologically indeterminate categories, were stained using aqueous methylene blue (MB) solution, imaged, and analyzed. Fluorescence emission images yielded diagnostically relevant information on cytomorphology. Significantly higher MB Fpol was measured in thyroid cancer as compared to benign and normal cells. The results obtained from 12 indeterminate samples revealed that MB Fpol accurately differentiated benign and malignant thyroid nodules. Conclusions: The developed imaging approach holds the potential to provide an accurate and objective biomarker for thyroid cancer, improve diagnostic accuracy of cytopathology, and decrease the number of lobectomy and near-total thyroidectomy procedures.
Highlights
Epidemiological studies indicate that overall prevalence of thyroid nodules is between40 and 71% in adults [1,2]
Fine-needle aspiration cytology (FNAC) is the standard of care for preoperative evaluation of thyroid nodules that are suspicious for malignancy [6]
The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) is a standardized classification scheme used to group thyroid cytology specimens into one of six diagnostic categories: (I) nondiagnostic/unsatisfactory (ND/UNS), (II) benign, (III) atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS), (IV) follicular neoplasm/suspicious for a follicular neoplasm (FN/SFN), (V) suspicious for malignancy (SFM), and (VI) malignant [7]
Summary
Epidemiological studies indicate that overall prevalence of thyroid nodules is between40 and 71% in adults [1,2]. Fine-needle aspiration cytology (FNAC) is the standard of care for preoperative evaluation of thyroid nodules that are suspicious for malignancy [6]. While FNAC can provide a conclusive diagnosis for benign (category II) and malignant (category VI) thyroid nodules [8,9], overall diagnostic accuracy ranges from 60.2 to 68.8% when including aspirates within the indeterminate categories. Diagnostic accuracy of the standard of care fine-needle aspiration cytology (FNAC) remains a significant problem in thyroid oncology. Methods: In this double-blind study, we employed fluorescence emission and quantitative fluorescence polarization (Fpol) confocal imaging for sorting thyroid cells into benign/malignant categories. Samples were collected from malignant tumors, benign nodules, and normal thyroid epithelial tissues. The results obtained from 12 indeterminate samples revealed that MB Fpol accurately differentiated benign and malignant thyroid nodules
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