Haggi Mazeh
Thyroid surgeon Haggi Mazeh, MD, FACS, in the operating room at Hadassah-Hebrew University Medical Center in Jerusalem, Israel. Credit: Larry Luxner

JERUSALEM, Israel—As most types of cancer decline throughout the developed world, thyroid cancer inexplicably continues to rise. Yet the incidence of medullary thyroid carcinoma (MTC)—a relatively rare type that’s more difficult to treat than the far more common papillary and follicular types of thyroid cancer—has increased only slightly over the years.

Haggi Mazeh, MD, FACS, is chief of surgery at the Department of General Surgery within Hebrew University’s Hadassah Medical Center in Jerusalem. Dr. Mazeh, who specialized in endocrine surgery at the University of Wisconsin in Madison, is also known for having developed a method to diagnose thyroid cancer with 94% accuracy.

He said that papillary and follicular thyroid cancer account for more than 9 out of 10 cases of thyroid cancer globally; both carry a very good prognosis, in general.

Continue Reading

“The reason is that they’re well‑differentiated, in that they uptake iodine and their cells participate in the production of thyroid hormone,” Dr. Mazeh explained during an interview at Hadassah’s Mount Scopus campus overlooking East Jerusalem. 

By contrast, MTC is fast-growing, and it tends to spread to lymph nodes and beyond at higher rates than the other types. And thirdly, he said, radioactive iodine is “totally ineffective” in treating MTC.

“Medullary thyroid cancer, the 3rd most common type, comes not from the papillary or follicular cells but the C cells, or the parafollicular cells of the thyroid. These produce calcitonin, which we can use as a tumor marker,” Dr. Mazeh said, adding that MTC—which comprises around 3%-5% of all thyroid cancers—is still more common than anaplastic thyroid cancer, the rarest and by far the most aggressive type of thyroid cancer, and the one with the poorest prognosis.

“Surgical removal of the thyroid gland along with the involved lymph nodes is the mainstay of treatment of medullary thyroid cancer,” said Dr. Mazeh, who sees 10-20 new patients per year. But, he said, it’s important to correctly diagnose MTC prior to surgery, because some 25% of cases are genetic in nature.

Read more about the etiology of MTC

“We have to do a workup to include some evaluation of the genetic syndromes that are associated with medullary thyroid cancer,” he explained. “We also have to exclude the concurrent appearance of pheochromocytoma, which is a tumor of the adrenal glands that secretes adrenaline. We have to rule out the concurrent tumors in order to know which surgery goes first. If you have a pheochromocytoma, you go first to have an adrenalectomy. Only then do we treat the thyroid.”

Hebrew University’s Hadassah Medical Center’s Scopus campus in Jerusalem, Israel. Credit: Larry Luxner

For this reason, he said, an endocrinologist with experience—and preferably working at a specialized clinic—should do the workup. A CT scan is also usually done prior to surgery.

“Medullary thyroid cancers spread to lymph nodes quite early, much earlier than papillary and follicular. Therefore, I like to know the extent of disease before I start the surgery,” he said.  

While life expectancy for a patient diagnosed with MTC has not increased dramatically over time, Dr. Mazeh said “nowadays, we are more aware of medullary thyroid cancer, and we tailor the appropriate surgery, or extent of surgery, by evaluating the extent of disease in the neck by ultrasound, CT and calcitonin levels before surgery.”

Possible reasons for higher rates of thyroid cancer, in general, may include the increased use of neck imaging such as ultrasound and CT, as well as lifestyle changes, though as Dr. Mazeh said, “unfortunately, there’s nothing that anyone can do to avoid it.” He advises that “patients who have a familial history of medullary thyroid cancer should be investigated and evaluated by an experienced endocrinologist who can evaluate their risk.”

Among other accomplishments, Dr. Mazeh has performed prophylactic thyroidectomies on several children—in a procedure unique to MTC.

“Medullary thyroid cancer is the only circumstance where we do a prophylactic thyroidectomy in order to avoid the development of cancers in patients who we know 100% will develop medullary thyroid cancer over the years,” he said. “Patients have their genetic background evaluated by an endocrinologist and genetic workup, and we know their exact mutation. We can now tell patients that they have a super high increased risk for developing medullary thyroid cancer.”

In some cases, surgery is performed even on infants in their first year of life, he said. “These are babies with very small thyroids that we take out to prevent developing medullary thyroid cancer.”

In 2019, Dr. Mazeh and a colleague, Iddo Z. Ben-Dov, MD, PhD, senior physician at Hadassah’s Department of Nephrology, made headlines by developing what they called a “breakthrough” new method of identifying thyroid cancer.

Haggi Mazeh, MD, FACS, chief of general and endocrine surgery at Hebrew University’s Hadassah Medical Center in Jerusalem, Israel, with the Thyroid Cancer Survivors’ Association (ThyCa) handbook he translated into Hebrew. Credit: Larry Luxner

“Many thyroid biopsies are inconclusive. They cannot absolutely tell us whether it’s cancer or not,” he said, explaining that biopsies are done using by inserting a fine needle to aspirate cells in the small nodules that sometimes develop on the thyroid. But because of the small size of both the needle and the specimen, about one-third of such biopsies are indeterminate. 

If a subsequent biopsy is also inconclusive, patients must either pay for a $3000 commercial molecular examination or have the thyroid either partially or completely removed.

“Current available commercial tests are very expensive and not 100% accurate. What I have investigated is the role of microRNAs, which are small, tiny molecules that evaluate the presence of malignancy with much better accuracy than current molecular testing,” he said. 

The miRNA panel Dr. Mazeh’s team came up with is based on different expressions of miRNA in malignant and benign thyroid nodules. The samples came from 274 patients at Hadassah’s Mount Scopus campus. Dr. Mazeh is now looking for funding to boost the number of samples tested in order to prove the accuracy of their findings.

But these tests are only for well-differentiated thyroid cancers, not MTC.

Asked if his research could improve upon what’s being done in American laboratories, Dr. Mazeh responded: “Yes, I think so. We’re not there yet. It’s far from being commercialized as the tests now available in the US, but maybe one day, we’ll get there.”