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Jared Kushner's Thyroid Cancer

— Trump's son-in-law and former White House advisor announced the diagnosis in his memoir

MedpageToday
A photo of Jared Kushner

In an forthcoming memoir entitled Breaking History: A White House Memoir, Jared Kushner, 41, writes that he was secretly treated for thyroid cancer in 2019. The former White House senior advisor and Trump son-in-law : "On the morning that I traveled to Texas to attend the opening of a Louis Vuitton factory, White House physician Sean Conley pulled me into the medical cabin on Air Force One, 'Your test results came back from Walter Reed. It looks like you have cancer. We need to schedule a surgery right away.'"

The cancer was caught early; however, Kushner's physician, Thomas Fahey, MD, of NewYork-Presbyterian Hospital in New York City, concluded that surgery was the most appropriate option. In the surgery performed just before Thanksgiving, a "substantial part" of his thyroid was removed. Although Kushner had been warned that the surgery could alter his voice for a significant period, he writes that: "Luckily, the impact was minimal."

Thyroid Cancer

There are four main types of thyroid cancer:

Papillary thyroid cancer (PTC): This type makes up about 80% of all thyroid cancers in the U.S. It originates in follicular cells and tends to grow slowly. Microscopically, the unique characteristic feature of PTC is papillae, consisting of layers of tumor cells surrounding a fibrovascular core.

Follicular thyroid cancer (FTC): Accounting for about 15% of all thyroid cancers, it begins in follicular cells and grows slowly. Microscopically, FTC can vary from well to poorly differentiated.

Medullary thyroid cancer (MTC): This type makes up about 3-4% of all thyroid cancers. It begins in the parafollicular C cells of the thyroid and can, therefore, result in abnormally high levels of calcitonin. Its histology includes spindle-shaped cells with no follicle formation. Amyloid deposits are typically present.

Anaplastic thyroid cancer: Comprising only 2% of thyroid cancers, it also originates in the follicular cells of the thyroid. However, these cancer cells grow and spread quickly and are very difficult to control. The usual histologic variants are spindle-cell, pleomorphic giant cell, and squamous variants.

Well-differentiated tumors (papillary and follicular thyroid cancer) are highly treatable and usually curable, notes the National Library of Medicine's PDQ summary. Poorly differentiated and undifferentiated thyroid tumors (anaplastic thyroid cancer) are less common, aggressive, metastasize early, and have a poorer prognosis.

Medullary thyroid cancer has an intermediate prognosis. It tends to grow slowly. About 25-30% of cases occur as part of a disease syndrome called multiple endocrine neoplasia, type 2 (MEN2) caused by mutations in the RET gene. Mutations in RET are also found in more than 60% of non-MEN2 medullary thyroid cancers.

Epidemiology and Risk Factors

According to the National Cancer Institute's Surveillance, Epidemiology, and End Results Program (): Thyroid cancer comprises about 2% of new cancer diagnoses in the U.S. It is estimated that there will be 43,800 new cases this year and 2,230 deaths from thyroid cancer, which is 0.4% of all cancer deaths. The 5-year relative survival rate is 98.4%.

Thyroid cancer is most prevalent between 25 and 65 years of age (median age 51) and affects women about three to four times more often than men.

Approximately 1.2% of men and women will be diagnosed with thyroid cancer at some point during their lifetime. In 2019, there were an estimated 915,664 people living with thyroid cancer in the United States.

Risk factors for thyroid cancer include the following:

  • History of radiation therapy administered in infancy or childhood (may occur as early as 5 years post exposure or up to more than 20 years later)
  • Radiation exposure from nuclear fall-out
  • Family history of thyroid disease or MEN2 syndrome
  • RET gene mutation or other chromosomal aberrations, including NTRK1 and MET gene overexpression
  • A history of goiter
  • Asian race

Signs and Symptoms

Thyroid cancer may not cause early signs or symptoms. It is sometimes found as a neck nodule noticed by a patient or during a routine physical exam. Signs or symptoms may occur as the tumor gets bigger:

  • A nodule in the neck
  • Difficulty breathing
  • Difficulty swallowing
  • Pain when swallowing
  • Hoarseness
  • Fever
  • Weight loss
  • Anorexia

Thyroid cancer commonly presents as a so-called cold nodule. It is detected as a palpable thyroid gland during a physical exam and, when evaluated with iodine I-131 scans, scintigraphy shows that the isotope is not taken up in an area of the gland. The overall incidence of cancer in a cold nodule is 12-15%, but it is higher in people younger than 40 years and in people with calcifications present on preoperative ultrasonography.

Treatment

Standard treatment options for localized/regional papillary and follicular thyroid cancer are as follows, according to the PDQ summary:

"Surgery is the therapy of choice for all primary lesions. Surgical options include total thyroidectomy or lobectomy. The choice of procedure is influenced mainly by the age of the patient and the size of the nodule. ... The objective of surgery is to completely remove the primary tumor, while minimizing treatment-related morbidity, and to guide postoperative treatment with RAI [radioactive iodine]. The goal of RAI is to ablate the remnant thyroid tissue to improve the specificity of thyroglobulin assays, which allows the detection of persistent disease by follow-up whole-body scanning."

Given the high incidence of multicentric involvement of both lobes of the gland and the possibility of dedifferentiation of any residual tumor to the anaplastic cell type, total thyroidectomy is common.

Thyroid lobectomy alone may be sufficient to treat low risk lesions under 1 cm that are unifocal, intrathyroidal papillary carcinomas if there hasn't been any previous head and neck irradiation or radiologically or clinically involved cervical nodal metastases. While it brings fewer complications, some 5-10% of patients will have a recurrence in the thyroid after a lobectomy.

Ablative doses of RAI after surgery decrease recurrence among high-risk patients with papillary and follicular carcinomas.

Other than lobectomy patients, all will require thyroid hormone replacement therapy after surgery. Supratherapeutic doses of thyroid hormone are routinely administered to suppress thyroid stimulating hormone (TSH) levels after thyroidectomy, which improves progression-free survival albeit not overall survival. The degree of TSH suppression recommended depends on the risk of recurrence and the comorbidities of the patient.

For metastatic papillary and follicular thyroid cancer, PDQ notes: "Total thyroidectomy is still recommended as the initial treatment for metastatic papillary or follicular thyroid cancer. RAI is the second treatment and is given to ablate the remnant thyroid and treat the metastatic disease."

Standard treatment for patients with iodine-sensitive thyroid cancer consists of surgery, RAI therapy and thyroid suppression therapy. For those with iodine-resistant thyroid cancer, surgery and thyroid suppression therapy may be supplemented with external-beam radiation therapy (EBRT), targeted therapy, or both. Sorafenib (Nexavar) and lenvatinib (Lenvima) are orally active, multitargeted tyrosine kinase inhibitors that have been approved for use in locally recurrent or metastatic, progressive, differentiated thyroid carcinoma that is refractory to radioactive iodine treatment.

For medullary thyroid cancer, treatment is total thyroidectomy unless there is evidence of distant metastasis. In patients with clinically palpable MTC, the incidence of microscopically positive nodes is more than 75%. Routine central and bilateral modified neck dissections are generally done. When cancer is confined to the thyroid gland, the prognosis is excellent.

EBRT has been used for palliation of locally recurrent tumors without evidence that it provides any survival advantage.

Standard treatment options for locally advanced and metastatic MTC include targeted therapy and palliative chemotherapy. Drugs that are approved for advanced/metastatic MTC include the tyrosine kinase inhibitors vandetanib (Caprelsa) and cabozantinib (Cometriq) and the RET kinase inhibitors selpercatinib (Retevmo) and pralsetinib (Gavreto).

Palliative chemotherapy has been reported to produce occasional responses in patients with metastatic disease, but no single drug regimen can be considered standard. Some patients with distant metastases will experience prolonged survival and can be managed expectantly until they become symptomatic.

Current clinical trials for the treatment of thyroid cancer can be found at .

Michele R. Berman, MD, is a pediatrician-turned-medical journalist. She trained at Johns Hopkins, Washington University in St. Louis, and St. Louis Children's Hospital. Her mission is both journalistic and educational: to report on common diseases affecting uncommon people and summarize the evidence-based medicine behind the headlines.