J Cancer 2020; 11(24):7276-7282. doi:10.7150/jca.46086 This issue
1. Department of Pathology, National Cancer Center/ National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College.
2. Department of Ultrasound, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College.
*These authors contributed equally to this work.
Objective: The management of indeterminate thyroid nodules is challenging. Molecular testing has emerged as a promising method for stratifying this gray area of fine-needle aspiration (FNA) cytology. Next-generation sequencing (NGS) can be used to test a large variety of genetic changes with very small amounts of nucleic acids obtained from FNA samples.
Methods: Thyroid FNA assays were classified according to the Bethesda System for Reporting Thyroid Cytopathology after routine ThinPrep® slide preparation. Indeterminate nodules with surgical outcomes were assayed with an 18-gene NGS panel with the residual ThinPrep® material, including nodules categorized as atypia of undetermined significance (AUS)/follicular lesions of undetermined significance (FLUS) or follicular neoplasm (FN)/suspicious for a follicular neoplasm (SFN). We evaluated the diagnostic efficacy of the 18-gene panel for thyroid malignancies and potential malignancies and compared it with a well-accepted examination, ThyroSeq v2 testing.
Results: A total of 36 indeterminate nodules were assayed, seven were categorized as AUS/FLUS and 29 as FN/SFN. All of them had adequate DNA for the NGS procedure. When noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) was considered malignant, the risk of malignancy was 71.4% for AUS/FLUS nodules, and 69.0%for FN/SFN nodules. The 18-gene panel showed 72.0% sensitivity, 72.7% specificity, 85.7% positive predictive value (PPV), and 53.3% negative predictive value (NPV) in identifying malignancies and potential malignancies in the indeterminate nodules. Compared with a multicenter report from ThyroSeq v2 testing, 18-gene panel showed a lower NPV (p=0.005), but a higher PPV (p=0.02).
Conclusions: NGS assays are feasible on residual ThinPrep® material, with the advantage of not requiring additional FNA procedure. The 18-gene panel testing can be used as a 'rule in' test for surgical management based on indeterminate nodules and showed a lower NPV but a higher PPV compared to ThyroSeq v2 testing.
Keywords: fine-needle aspiration, cytology, thyroid nodules, thyroid cancer, molecular diagnosis