Endocrine Abstracts

There are three main applications for molecular genetic testing in thyroid pathology:

1. As part of an integrated approach of careful clinical, ultrasound and FNBC assessment with local outcome data molecular analysis of fine needle biopsy cytology is able able to improve diagnostic outcomes for thyroid nodules by identifying patients with an indeterminate FNBC as most likely benign with < 5% false negatives and thus obviating diagnostic lobectomy or by identifying patients for upfront total thyroidectomy as definitive surgical treatment

2. 70% of high risk thyroid cancer patients develop a structural recurrence after total thyroidectomy and radioiodine treatment. Revision surgery and/or a second RAI treatment lead to remission in only 42 - 51% of these patients. Therefore, early prospective systematic detection of actionable driver mutations for thyroid cancer patients with local relapse or distant metastasis is needed to guide new targeted treatments such as NIS re-expression to re-enable RAI treatment or treatment with RET or NTRK inhibitors, ALK inhibitors, PAX8/PPARG agonists or emerging off label drugs. However, lack of systematic molecular analysis is the missing piece limiting access to emerging targeted and translational therapies for advanced thyroid cancer. All BRAF mutation-negative patients with progressive structural incomplete response to total thyroidectomy and RAI treatment, and ATA high/intermediate recurrence risk patients with progressive structural incomplete response, should be screened for NTRK and RET gene fusions to enable early intervention.

3. Several studies have reported large interobserver variability for the differential diagnosis between thyroid adenomas/adenomatous nodules and FTCs and other thyroid cancer histologies. Therefore, the current histology-based classification of thyroid tumors will ultimately most likely evolve into a blended histologic and molecular classification of thyroid tumours like for other endocrine tumors or other cancers.