DTC: Histological Subtypes and Tumor Differentiation

Lori J. Wirth, MD: I agree that one of the interesting things about thyroid cancer is that it’s not a one-size-fits-all operation. There are varying histologies. When we’re thinking about differentiated thyroid cancer, papillary thyroid cancer is the most common type. But we also see follicular thyroid cancers; and Hurthle cell thyroid cancers, we now know they are their own entity, they’re not a subtype of follicular thyroid cancers, as we once thought. Even poorly differentiated thyroid cancers are included in the group of patients with differentiated thyroid cancer. Those 4 different entities have different natural histories and different underlying biology. Yet to some extent, at initial diagnosis, they’re all treated the same, right?

Jennifer Sipos, MD: Right. I do think it’s important for us to understand the differences, not only in the histology, but also in the phenotype of these tumors. We think about histologic differences between the 4 types that you just discussed, but we also have to think about the extent of tumor differentiation in that conversation. Within the subtype of papillary thyroid cancers, the most common cancer, most of them are very well-differentiated tumors that behave very well. They’re indolent tumors. But then we can have, along that spectrum of differentiation, tumors that are less thyroid-like and less well-differentiated. Therefore, they behave much more aggressively. They can be all the way to the end of the spectrum, where they’re undifferentiated tumors, or anaplastic tumors. Within each of those histologic subtypes, we have to consider the different degree of differentiation that helps us to predict the biologic behavior of these tumors.

Also, that conversation includes some discussion of the genomics of these individual tumors and understanding how that impacts their behavior. As you mentioned with Hurthle cell tumors, we now understand these are distinct from follicular tumors. Part of that stems from understanding the genomics of these tumors. They look very different genetically from follicular tumors and papillary tumors. Understanding that genomic background helps us to also go forward with the treatment component of these tumors.

Lori J. Wirth, MD: Is it fair to say that, regardless of the histologic subtype of an initially diagnosed thyroid cancer, most patients are going to have surgery?

Jennifer Sipos, MD: It’s not always the case, and we’re certainly moving into a really exciting area in thyroid cancer research and management. This is a rapidly evolving field in which we are starting to understand that many of these tumors behave very well. Maybe they don’t necessarily need surgical intervention. As I alluded to earlier, 10% to 15% of people walking around have a small thyroid cancer, and if we go looking hard enough for it, we’re going to find it. Perhaps those tumors, if we left them alone, weren’t going to become aggressive tumors and manifest themselves in any way, had we not gone looking for them. Maybe we can simply observe them.

We’ve been following these data now for about 10 years. Centers in Japan have been observing small thyroid cancers, rather than operating on them. The consensus in the Japanese studies, and now in some of the evolving United States studies, the numbers are remarkably consistent in showing that it’s the minority of those small cancers that progress when they’re observed. We can take away that perhaps there’s a decent percentage of patients in whom observation alone would be adequate therapy, rather than proceeding with the traditional mode of surgery, followed by possible radioiodine.

Lori J. Wirth, MD: Jen, who are the patients in your clinic who you feel meet the criteria for observation?

Jennifer Sipos, MD: There are a number of things that we should consider in this. One is the appearance of the tumor on ultrasound. How big is the tumor, and what is the size threshold for observation, whether the tumor is 1 cm or less, or some studies are now using 2 cm or less as a threshold for observation. Then, there’s the sonographic appearance of the nodule. Does it look like there’s extrathyroidal extension? If so, maybe that suggests a more aggressive tumor that we wouldn’t want to observe. Does it look like a blander-appearing nodule that is well-contained within the thyroid and isn’t posing a threat of extending outside the thyroid into surrounding tissue? That’s one component. We look at the tumor itself.

The other piece of it is looking at the patient. We know from the Japanese studies and looking retrospectively at who progressed in multivariate analysis that tumors that are larger were more likely to progress. But also, those tumors that were present in younger patients were more likely to progress. If we take that back to our clinic, we may say, “You’re younger. There’s a longer lifespan ahead of you whereby this tumor may continue to grow and progress.” We’re more likely to remove it earlier, versus an older patient, or someone who has multiple comorbid conditions. In that situation, thyroid cancer falls pretty low on the spectrum of concerning clinical factors. Maybe there are other primary malignancies, uncontrolled hypertension, or cardiovascular disease that may take a higher precedence over treating their thyroid cancer.

Transcript Edited for Clarity