Background Molecular testing of thyroid nodules is a diagnostic tool used to better understand the nature of thyroid nodules. The aim of this study is to better comprehend the relationship between specific mutations and aggressive behavior of the tumour as demonstrated on postoperative pathological analysis. Methods A retrospective chart review of 103 cases was performed. Included were patients who had undergone molecular testing using a panel that tests for 9 mutations (ThyGenX®) and were found to have malignant tumours. The following gene alterations were found pre-operatively in the nodules: BRAF V600E (n = 32), BRAF K601E (n = 4), NRAS (n = 11), HRAS (n = 4), KRAS (n = 3), RET/PTC1 rearrangement (n = 1), TERT promoter (n = 2), PAX8-PPARγ rearrangement (n = 1), and 45 cases where no mutation was detected. Aggressive behavior was defined by extra-thyroidal extension (ETE), lymph node metastasis (LN+), and the following variants of papillary thyroid carcinoma: tall cell, solid, diffuse sclerosing, columnar cell and hobnail. Chi-squared testing was performed to compare groups. Results The group with BRAF V600E, RET/PTC1 rearrangement, and TERT promoter mutations was associated with ETE 37.1%, and LN+ 45.7% of the time compared to 4.3 and 13.0% in the group with other mutations, and 4.4 and 4.4% in the group with no mutations (p-value 0.02, p-value < 0.001, p-value 0.006). In addition, the BRAF V600E, RET/PTC1 rearrangement, and TERT mutations group demonstrated tall cell variants (17.1%), columnar cell variants (5.7%), and hobnail variants (3%). The other mutations group demonstrated columnar cell variants (4.3%), and the no mutations group demonstrated solid variants (2.2%). Conclusions In this study, BRAF V600E, RET/PTC1 rearrangement, and TERT mutations were associated with aggressive behaving thyroid malignancies as defined above. Molecular testing may be a useful method to anticipate aggressive tumour types and therefore assist in planning the extent and timing of surgery.

Background Molecular testing has been used for cytologically indeterminate thyroid nodules (Bethesda III and IV), where the risk of malignancy is 10–40%. However, to date, the role of molecular testing in cytologically suspicious or positive for malignancy (Bethesda V and VI) thyroid nodules has been controversial. The aim of this study was to determine whether patients who had molecular testing in Bethesda V and VI thyroid nodules had the optimal extent of surgery performed more often than patients who did not have molecular testing performed. Methods A retrospective chart review of 122 cases was performed: 101 patients from the McGill University teaching hospitals and 21 patients from the Hillel Yaffe Medical center, Technion University. Patients included in the study were those with Bethesda V or VI thyroid nodules who underwent molecular testing (ThyGenext® or ThyroseqV3®) (McGill n = 72, Hillel Yaffe n = 14). Patients with Bethesda V or VI thyroid nodules who did not undergo molecular testing were used as controls (McGill n = 29, Hillel Yaffe n = 7). Each case was reviewed in order to determine whether the patient had optimal surgery. This was defined as total thyroidectomy in the presence of either a positive lymph node, extrathyroidal extension, or an aggressive pathological variant of papillary thyroid carcinoma (tall cell, hobnail, columnar cell, diffuse sclerosing, and solid/trabecular) documented on the final pathology report. In all other cases, a lobectomy/hemi/subtotal thyroidectomy was considered as optimal surgery. Chi-squared testing was performed to compare groups. Results When molecular testing was done, 91.86% (79/86) of surgeries in the molecular testing group were optimal, compared to 61.11% (22/36) in the control group. At McGill University teaching hospitals and at Hillel Yaffe, 91.67% (66/72) and 92.86% (13/14) of surgeries in the intervention group were considered as optimal, respectively. This compares to 58.62% (17/29) at McGill and 71.43% (5/7) at Hillel Yaffe when molecular testing was not performed (p = .001, p = .186). Conclusions In this study, molecular testing in Bethesda V and VI thyroid tumors significantly improved the likelihood of optimal surgery. Therefore, molecular testing may have an important role in optimizing surgical procedures performed in the setting of Bethesda V and VI thyroid nodules. Prospective studies with larger sample sizes are required to further investigate this finding. Graphical abstract