Maria E. Cabanillas, MD: Sure. Differentiated thyroid cancer is usually diagnosed after a biopsy of a thyroid nodule or thyroid mass, either by fine-needle aspiration or by core biopsy. Oftentimes it’s incidental. For example, the patient maybe was in the emergency department after a motor vehicle accident, and they did a CT and found a nodule. Most of the time these are asymptomatic. There are ultrasound features that suggested a nodule could be malignant because a majority of nodules are not malignant.

Things such as microcalcifications we see in papillary thyroid cancer. Other useful ultrasound features are hypoechogenicity and irregular margins in taller and wider shapes. If you see those, we usually want to biopsy those nodules. Once that’s been biopsied, it’s in the pathologists’ and cytopathologists’ hands. They will typically do different markers such as thyroglobulin, DTF1, and PAX8, which are positive in most differentiated thyroid cancers. Whereas with medullary thyroid cancer, calcitonin would be the positive stain.

As I said, most of these cases are asymptomatic. Some patients have a history of thyroid nodules that have been observed, and some have been biopsied in the past. Some patients have a history of goiter. More advanced cases, though, can become symptomatic. Some patients with larger tumors will present with dysphagia, hoarseness, visible mass. Particularly in anaplastic thyroid cancer, those are the symptoms we typically see. Sometimes they can have pain in their ear, which is probably just referred pain.

Patients will rarely present with dyspnea, except in anaplastic thyroid cancer. This is often associated with very advanced or aggressive disease. For example, if the trachea is being deviated by a large nodule or if there is disease growing into the trachea, then those patients—a lot of distant metastatic disease, of course—can be symptomatic. But even in patients who have distant metastatic disease with differentiated medullary thyroid cancer, they’re often completely unaware that they have distant metastatic disease because these’re usually asymptomatic.

Lori Wirth, MD: You mentioned the nuances that can be seen on ultrasound. Also, the cytopathology interpretation can be nuanced as well. Not everyone works in a center that has a great depth of expertise in thyroid cancer, cytopathology, and ultrasound doing thyroid ultrasound. What advice do you have for somebody who might not know how good their ultrasound radiologist is or might not have access to good cytopathology in terms of working up a suspicious thyroid nodule?

Maria E. Cabanillas, MD: That’s a great question. I know that when Afirma started a lot of people used it because they didn’t trust their cytopathology. Companies that look at different features of thyroid nodule cytopathology have a cytopathologist that reviews the slides and determines whether they even need to do any type of advanced molecular typing on the nodule before that happens in order to save money. If you can say yes, this looks like a papillary thyroid cancer, there’s no need to do an expensive test to show that. That’s 1 avenue—many of these tests for nodules are available. Afirma will have a cytopathologist look at it for you. You can also refer patients to larger centers, and then there can be a review of the cytopathology. In some centers they’ll give a second opinion on the cytopathology without having the patient go to that center.

Lori Wirth, MD: You’re talking about the Afirma molecular diagnostics commercial test for the diagnostic interpretation of FNA [fine-needle aspiration] of a thyroid nodule. Another large commercially available test is ThyroSeq. There are others, but those are the 2 used most frequently.

Maria E. Cabanillas, MD: I don’t know if they all have cytopathologists that look at these. Naifa would know better. She runs our thyroid nodule clinic at [The University of Texas] MD Anderson [Cancer Center].

Naifa L. Busaidy, MD, FACP, FACE: Just to come back to Lori’s question, if you don’t have good cytopathology, then work as hard as you can to identify a commercial or another local institution, because it’s key. We know that there’s a percentage of thyroid cancers and thyroid nodules where good pathologists disagree. That controversy is OK, but identify something consistent and have that conversation when you’re not sure.

Transcript edited for clarity.