Thyroid cancer is a prevalent endocrine malignancy, affecting millions globally. While often manageable, accurately diagnosing thyroid nodules presents a challenge for medical professionals. Advanced diagnostic techniques are sometimes necessary to identify the nature of these growths.
Thyroid Cancer and the Need for Clarity
Thyroid nodules are common, with studies estimating their prevalence to be between 20% and 76% in the adult population. The initial diagnostic approach involves an ultrasound, followed by a Fine Needle Aspiration (FNA) biopsy. This procedure collects cells from the nodule for microscopic examination.
FNA biopsies can usually indicate whether a nodule is benign or cancerous. However, a challenge arises when FNA results are “indeterminate,” meaning the microscopic examination cannot definitively classify the nodule. These indeterminate results, often falling into Bethesda categories III or IV, can occur in up to 30% of cases. In such situations, further clarification is needed.
The Purpose of Molecular Testing for Thyroid Cancer
Molecular testing for thyroid cancer analyzes genetic material within thyroid cells to identify specific mutations or alterations linked to cancer. This advanced diagnostic tool clarifies indeterminate thyroid nodules. By providing more precise information than cytology alone, molecular testing helps clinicians determine the likelihood of a nodule being malignant. This can prevent unnecessary surgeries for benign nodules, as a significant majority (70-80%) of indeterminate nodules are ultimately found to be benign.
Molecular testing also guides treatment strategies for confirmed malignant cases. Identifying specific genetic markers can predict the aggressiveness of the disease and inform decisions regarding the extent of surgery or the need for targeted therapies. The integration of molecular testing into management guidelines, especially for Bethesda III or IV nodules, reflects its role in refining thyroid cancer diagnosis and patient care.
How Molecular Testing is Performed
Molecular testing uses the same sample material obtained from a Fine Needle Aspiration (FNA) biopsy. After the initial FNA, the collected cellular material is sent to a specialized laboratory for processing. In the lab, DNA and/or RNA are extracted from the thyroid cells.
Once extracted, these genetic materials are analyzed using various techniques. Common methods include Polymerase Chain Reaction (PCR), which amplifies specific DNA sequences to identify mutations, and Next-Generation Sequencing (NGS), which rapidly sequences large portions of the genome to detect a wide range of genetic changes. Some tests may also use Multiplex Ligation-Dependent Probe Amplification (MLPA) or Fluorescence In Situ Hybridization (FISH). These techniques identify genetic alterations such as point mutations, gene fusions, or rearrangements associated with thyroid cancer.
Interpreting Molecular Test Results
Interpreting molecular test results involves identifying specific genetic alterations that indicate the likelihood of cancer and influence treatment decisions. Common genetic mutations analyzed include BRAF, RAS, RET/PTC rearrangements, PAX8/PPARĪ³ rearrangements, and TERT promoter mutations. The presence of a BRAF mutation, particularly BRAF V600E, is associated with papillary thyroid carcinoma and may indicate a higher risk of recurrence.
RAS mutations are common in thyroid tumors, found in papillary or follicular thyroid carcinomas. RET/PTC rearrangements are linked to papillary and medullary thyroid carcinomas, while PAX8/PPARĪ³ rearrangements are associated with follicular thyroid carcinoma. The detection of TERT promoter mutations, especially alongside BRAF V600E, suggests a more aggressive tumor and is associated with advanced stages and increased mortality.
A positive finding for any of these mutations indicates malignancy and helps refine clinical management. For instance, identifying specific mutations can guide the use of targeted therapies that are more effective against certain genetic profiles. If molecular testing yields a benign result, it can reduce the risk of malignancy, allowing for non-operative management and helping patients avoid diagnostic surgery. Ultimately, these results are interpreted by a multidisciplinary medical team, including endocrinologists, surgeons, and pathologists, in conjunction with the patient’s overall clinical findings to determine the most appropriate course of action.