Molecular Profiling of Thyroid Nodules
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At UCLA, thyroid nodules with indeterminate biopsy results are sent out for an additional molecular marker test. After fine-needle aspiration biopsy (FNA), cells sampled from thyroid nodules under initial analysis with cytopathology – this is where an expert cytopathology doctor examines the cells under the microscope after preservation and staining. Cytopathology takes about 5 days to complete, and yields the following possible results:
- Benign cytopathology (70% of results).
- Indeterminate cytopathology (25% of results).
- Malignant cytopathology (5-10% of results).
Important things to know are that benign cytopathology is highly reassuring, as it carries a false negative rate of <4%. Likewise, malignant cytopathology is also highly convincing, as it carries a false positive rate of <1%. Indeterminate cytopathology represents a gray zone where the risk of thyroid cancer ranges from 10-35%. Indeterminate cytopathology encompasses findings of atypia of undetermined significance (AUS), follicular lesion of undetermined significance (FLUS), and follicular neoplasm (FN). You may see these terms on your biopsy report.
Prior to 2012, it was standard practice to recommend thyroid lobectomy to patients with indeterminate thyroid nodules. While we did not want to “miss” a possible thyroid cancer, this approach also led us to surgically remove many benign nodules. Indeed about 75% of these nodules were ultimately found to be benign after surgery. Performing molecular testing on indeterminate thyroid nodules helps us to better categorize these nodules as benign or malignant based on the DNA and/or RNA patterns inside. Molecular analysis typically takes 2 weeks to complete (this is in addition to the initial 5 days for the cytopathology result).
Slightly more than half of molecular tests for indeterminate thyroid nodules show a benign or negative result; these patients can generally avoid surgery. If molecular testing is “suspicious” or “positive” for thyroid cancer, in most cases we recommend thyroid surgery (usually lobectomy) to remove the portion of the thyroid with the suspicious nodule. Less commonly, observation may be an appropriate option.
It is very rare that patients end up having a “surprise” thyroid cancer because of a false negative test. Still, it is UCLA ’s standard of care to have a safety net and follow every patient after molecular testing, regardless of their result. Those patients will get ultrasounds every 6-12 months to ensure that nodules do not grow or change in appearance.