Molecular Markers

A fine needle aspiration biopsy is the initial diagnostic step in the workup of a thyroid nodule.  In the simplest terms, the result will be returned as one of the following categories:

  • Nondiagnostic – not enough cells to give an accurate risk of thyroid cancer
  • Benign – normal appearing nodule which does not need to be removed
  • Indeterminate – not quite normal appearing cells, but not diagnostic of cancer either
  • Cancer – 99-100% risk of malignancy, and surgery is recommended

For indeterminate nodules on biopsy, there is approximately a 15% chance of malignancy, but an 85% chance that it is a benign nodule which does not need to be removed.   In the past, nodules which were indeterminate on cytology have either been biopsied again in approximately 3 months, or removed surgically to obtain a definitive diagnosis.  Do the math, and this results in a high number of thyroid surgeries with benign nodules on the final pathology.  In other words, these nodules really didn’t need to be removed.

Molecular markers have been developed in order to provide additional information about which thyroid nodules need to be removed with surgery and which can safely be observed.  Cells from the thyroid biopsy are processed to detect the presence of genetic mutations found in thyroid cancers.  This can decrease the risk of thyroid malignancy to 3-4%, or increase it to 80-95%.  There are significantly more of the low risk nodules which can safely be observed, but those that are higher risk need to be removed with surgery.

There are two main tests for molecular markers.  The first is known as the Thyroseq, which was developed at the University of Pittsburgh Medical Center (UPMC) Division of Molecular and Genomic Pathology.  It is readily available through CBL Pathology, where high volume thyroid cytopathologists examine the cells and then send the indeterminate specimens to Pittsburgh to be analyzed with the Thyroseq.

The other test is the Afirma, which was developed by Veracyte.  The same principle applies in that the cells from indeterminate specimens are processed to detect the presence of mutations which are found in thyroid cancer cells.  This is called the genomic sequencing classifier (GSC), and this can decrease the risk of thyroid cancer to acceptable levels for continued surveillance, or determine which nodules need to be removed with surgery.

Both of these tests are important for thyroid specialists to determine which thyroid nodules can safely be observed because of their low risk of malignancy, or which nodules should be removed for complete histological analysis.  If positive, they can provide additional information about the type of thyroid cancer which may be present so that the appropriate surgery is performed upfront without the need for a second operation.