What information does molecular testing of thyroid nodules provide?

From the Guidelines

Molecular testing of thyroid nodules provides valuable genetic information that helps determine if a nodule is benign or malignant when fine needle aspiration (FNA) results are indeterminate, guiding clinical decision-making and reducing unnecessary thyroid surgeries. This testing identifies specific genetic mutations, such as BRAF, RAS, RET/PTC, and PAX8/PPARγ, which are frequently found in papillary and follicular thyroid cancers 1. The results help stratify cancer risk, with some mutations indicating a high likelihood of malignancy, while others suggest lower risk.

Key Findings

• Molecular testing is particularly useful for Bethesda category III and IV nodules, where traditional cytology cannot definitively rule out cancer 1.
• The BRAF V600E mutation occurs in approximately 45% of papillary carcinomas, making it a significant marker for malignancy 1.
• Different commercial tests are available, each with specific sensitivity and specificity profiles for detecting malignancy, such as Afirma, ThyroSeq, and ThyGeNEXT.

Clinical Implications

• Molecular testing reduces unnecessary thyroid surgeries by providing additional diagnostic clarity for the 15-30% of nodules with indeterminate cytology 1.
• This information guides clinical decision-making about whether surgery is necessary or if active surveillance is appropriate, ultimately improving patient outcomes and quality of life 1.
• The use of molecular diagnostics for indeterminate FNA results may help some patients with indolent nodules avoid surgery, as suggested by recent medical advances 1.

From the Research

Molecular Testing Information

Molecular testing of thyroid nodules provides several key pieces of information, including:

• The likelihood of malignancy in indeterminate thyroid nodules (Bethesda III and IV) 2, 3, 4, 5
• The underlying molecular drivers of thyroid cancer, which can support decision making in initial management planning 2
• Information on the molecular risk group profile of a thyroid nodule, which can help select the optimal surgical options 3
• Prognostic information, which can aid in decisions such as extent of surgery and post-therapy monitoring plans 6

Clinical Applications

The clinical applications of molecular testing for thyroid nodules include:

• Ruling out malignancy in indeterminate thyroid nodules, thereby avoiding unnecessary diagnostic surgery 2, 3, 4, 5
• Optimizing initial management in thyroid cancers with no evidence of high risk of recurrence of disease preoperatively 3
• Selecting the optimal surgical options, such as lobectomy versus upfront total thyroidectomy and central neck dissection 3
• Guiding the use of targeted therapies, such as mono-kinase inhibitors, in patients with advanced disease 2

Test Characteristics

The molecular tests for thyroid nodules have several key characteristics, including:

• High sensitivity and negative predictive value, making them useful for ruling out malignancy 2, 3, 4, 5
• Ability to reclassify indeterminate thyroid nodules as benign or malignant, thereby reducing the need for diagnostic surgery 3, 5
• Use of different technologies, such as DNA/RNA-based testing, RNA-based testing, and hybrid DNA/miRNA testing 2