Endocrine Abstracts

Background

Most thyroid nodules are benign, but therefore it is crucial to correctly stratify the malignancy risk of nodules to avoid unnecessary invasive procedures and/or surgery, but and still identify aggressive tumors. The aim of our study was to address the potential for improvement of malignancy detection in routine clinical setting using clinical examination, risk stratification of thyroid nodules on ultrasound using the American College of Radiology Thyroid Imaging Reporting and Database System (ACR TI-RADS) and fine-needle aspiration cytology (FNAC) concurrently with molecular diagnostics.

Methods

A prospective study in 105 patients was performed. DNA from FNA samples was used for next generation sequencing to identify mutations in genes: BRAF, HRAS, KRAS, NRAS and TERT. RNA was used for Real Time PCR to detect RET/PTC1, RET/PTC3 and ETV6/NTR3 rearrangements. All specimens were histologically confirmed. Multivariate regression (a method of orthogonal projections to latent structure, OPLS) was used for data evaluation.

Results

FNA samples were cytologically evaluated as Bethesda II (n = 16; 15.2%), III (n = 23; 21.9%), IV (n = 18; 17.1%), V (n = 24; 22.9%) and VI (n = 24; 22.9%). Histologically, 48 findings were malignant (45.7%); especially papillary thyroid carcinoma (93.8%); 54 were benign and 4 were borderline tumors (MB). Total detection rate of mutations was 4/54 in benign tissues, 41/48 in malignant and 1/4 in MB. Total detection rate of mutations was 4/16 in Bethesda II; 6/23 III; 3/18 IV; 14/24 V and 20/24 VI. The strongest relevant positive predictors for malignancy were the presence of genetic mutation (t-statistic = 14.10; P < 0.01), FNAC (10.39; P < 0.01), ACR TI-RADS (4.02; P < 0.01), positivity of anti-thyroglobulin antibodies (4.09; P < 0.01), TSH (3.6; P < 0.01), presence of neck resistance (2.86; P < 0.05) and lymphadenopathy (2.33; P < 0.05). In common, FNAC, ACR TI-RADS and genetic testing reached sensitivity 86.3% (95% CI 74.3–93.2), specificity 88.9% (95% CI 77.8–94.8) and diagnostic odds ratio 50.3 (15.7–161.2).

Conclusion

FNA molecular testing has seemed to have substantial potential for thyroid malignancy detection. Clinical examination, FNAC and risk stratification of thyroid nodules on ultrasound have been other relevant factors. However, a broader spectrum of molecular markers must be involved to make correct diagnosis in all patients in a routine clinical setting.