Let’s talk just very briefly about thyroid irradiation. Potential sources for thyroid irradiation include external beam irradiation or radioiodine fallout. There was a lot of childhood irradiation being done back in the 40’s and 50’s and there were many many cases of thyroid cancer noted in the adults of children who were exposed, for reasons that would certainly not be considered medically appropriate uses of radiation in this day and age. It is clear to me that children are more radio-sensitive than adults. Now we have radioactive fallout. Catastrophe; I’m sure many of you remember this. This was shortly after the Chernobyl reactor accident, and it truly has been a catastrophe in any number of different ways, not the least being sort of an epidemic of especially childhood thyroid cancer cases with fairly aggressive courses that have been noted. Beginning about four years after – it was a fairly short latency, actually – after the reactor accident. I guess hopefully we will never see another Chernobyl but on the other hand, as the events in Japan last week have proven, by no means are we going to be free from the potential risk of catastrophic nuclear accidents in the future.

Familial syndromes associated with papillary thyroid cancer: there are familial papillary thyroid cancer syndromes but a specific familial papillary gene has not been identified. Papillary cancer is seen in increased frequency with some GI syndromes, Gardener’s syndrome, familial polyposis, Cowden syndrome. Carney complex is the combination of myxomas, nodular adrenal cortical disease, Sertoli cell, testicular carcinomas and thyroid malignancies are also seen with increased frequency in that. A couple of pathologic variants of papillary thyroid cancer may be noted at the time of surgery, and sort of going from less aggressive to more aggressive are an encapsulated papillary thyroid cancer variant, the so-called follicular variant. These are tumors in which there is no gross papillary element present in the tumor, but the cytology of the individual cells is consistent with the papillary form. This has about an equal biologic behavior to ordinary papillary thyroid cancer. Of somewhat greater concern are the diffuse sclerosing variants, tall cell variant. There is another variant known as the columnar variant, which may be sort of a variant of tall cell variant, and an insular form which is fairly aggressive is also seen. So a couple of less common variants can be seen.

Follicular thyroid cancer accounts for about 15% of the thyroid cancer in the United States, and as I mentioned, more common in areas of chronic iodine deficiency. We touched on the issue that follicular carcinoma cannot be distinguished from follicular adenoma by aspiration, and so if that quandary remains, in general I will recommend surgery to the patient. The general spread of follicular carcinoma is by hematogenous spread to lung, bone, liver and brain. A specific variant form that is though to be a variant of follicular carcinoma is the so-called Hurthle cell carcinoma. Hurthle cells, which may be seen in a variety of different thyroid lesions, including many non-neoplastic conditions. So the presence of Hurthle cells is not in and of itself specifically a marker of a thyroid neoplasm. But occasionally one will see neoplasms which consist predominantly of oxyphilic cells with sort of a granular cytoplasm and this defines the Hurthle cell variant. One of the important issues in terms of Hurthle cell carcinomas, is that in comparison to follicular or papillary carcinoma, it is considerably less likely to take up radioiodine and therefore in one sense is effectively a surgical disorder. Many, although not all, investigators report a worsened prognosis compared to follicular carcinoma. It would hardly be surprising if this was in fact the case based on the fact that it appears to be a less differentiated tumor. But it’s not been a universal finding in all studies.