Molecular testing for cytologically suspicious and malignant (Bethesda V and VI) thyroid nodules to optimize the extent of surgical intervention: a retrospective chart review

J Otolaryngol Head Neck Surg. 2021 Apr 28;50(1):29. doi: 10.1186/s40463-021-00500-6.


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.

MeSH terms

  • Aged
  • Female
  • Humans
  • Male
  • Middle Aged
  • Molecular Diagnostic Techniques*
  • Mutation*
  • Proto-Oncogene Proteins B-raf / genetics
  • Retrospective Studies
  • Thyroid Cancer, Papillary / genetics
  • Thyroid Cancer, Papillary / pathology*
  • Thyroid Cancer, Papillary / surgery
  • Thyroid Neoplasms / genetics
  • Thyroid Neoplasms / pathology*
  • Thyroid Neoplasms / surgery
  • Thyroid Nodule / genetics
  • Thyroid Nodule / pathology*
  • Thyroid Nodule / surgery
  • Thyroidectomy


  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf