The frequency of thyroid cancer has increased since the 1960’s, and is one of the most common pediatric cancers. Before the 1980’s, children often received radiation treatments to the neck for certain types of cancer (Hodgkin’s disease) or respiratory problems. This has since been shown to cause thyroid cancer and accounted for 80% of thyroid cancer cases in previous years. Thyroid cancer after neck radiation is almost always papillary carcinoma. Another cause of thyroid cancer is treatment of previous cancers with certain anti-cancer drugs (alkylating agents). Specifically, treatment of Hodgkin’s disease has been shown to increase the risk of thyroid cancer 20 years later. Most thyroid cancers in children are papillary carcinoma, followed by follicular carcinoma (10%), and the rarely medullary carcinoma.
Papillary Carcinoma of the Thyroid Gland
Papillary carcinoma often (> 50%) presents with advanced disease at the initial diagnosis. This usually means the carcinoma has spread to the lymph nodes in the neck, but can mean spread to other locations. Even with spread to the lymph nodes in the neck, the prognosis is excellent.
Clinical features of Papillary Carcinoma
The most common way children with papillary carcinoma present initially to the doctor is with a thyroid nodule and enlarged neck lymph nodes. Sometimes the nodes have been present for years before the diagnosis is made. 20% of kids have spread to the lungs at initial presentation. 30% have invasion of local structures (esophagus, muscles, trachea) at diagnosis. 80-90% of children have some lymph node involvement at presentation.
In most cases, a thyroid nodule in children is treated by thyroid lobectomy, (removal of half the gland). This is sometimes performed even after an FNA shows benign disease. This aggressive management in children is because of the increased chance of cancer (malignancy) compared to adults and because FNA samples only a small part of the nodule and may miss a malignancy. During the thyroid lobectomy, a frozen section can be performed. This involves freezing the sample and looking at a small piece under the microscope. This method is less accurate than the permanent specimens which will take three days to prepare and perform. If the final pathology demonstrates a papillary carcinoma, the child is generally re-operated on to remove the rest of the gland (total thyroidectomy). This is performed a few days after the original surgery before scarring can make the operation more difficult.
If lymph nodes are involved, a central lymph node dissection is also performed. This involves removing nodes between the jugular veins, from the top of neck (hyoid bone) to the bottom of the neck (sternal notch). If the cancer is more aggressive and has invaded other structures, such as nerves or muscle, these should be removed as well. If all the cancer is not removed the outcome is significantly worse.
Risks of the operation involve bleeding or injury to the recurrent laryngeal nerve and parathyroid glands. The thyroid gland is a very vascular structure, and therefore on rare occasions bleeding complications can occur. The recurrent laryngeal nerve runs beneath the gland on both sides of the neck (left and right) and controls the vocal cords. Injury to the nerve occurs in 1 in 100 patients. If injury to the nerve occurs on one side, it simply causes changes in the voice. In the rare case of injury to both nerves, one can have significant breathing difficulties. More common than injury is temporary weakness of the nerve which affects the voice for six weeks. There are four parathyroid glands in the neck. They are on the edges of the thyroid gland or even embedded in the gland and are involved in regulating the body’s calcium. During a thyroidectomy, they can be injured or removed inadvertently. Only one parathyroid is needed for normal function. If the calcium level in the blood is low, symptoms may develop: tingling around the lips or contraction of muscles. If a parathyroid gland is removed, it can be implanted into the muscles of the neck or arm and function normally. The real risk is only after a total thyroidectomy, and calcium levels should be monitored in this setting.
Six weeks after surgery, a child with papillary carcinoma and a total thyroidectomy undergoes a thyroid scan. Iodine-131 is given to determine if there is residual thyroid tissue in the neck or elsewhere in the body. If present, a larger dose of iodine-131 can be given to kill any residual thyroid disease.
Even in the setting of metastatic papillary thyroid cancer that has spread to other parts of the body (metastatic), most children do very well. Total thyroidectomy followed by iodine-131 will remove all the cancer in most children. Occasionally additional doses of iodine-131 are necessary. After total thyroidectomy, the child will require thyroid replacement (thyroxine) for life.
Follicular Carcinoma of the Thyroid
Follicular carcinoma is rarer in children than papillary carcinoma. It grows slowly and spreads (metastasizes) by the blood system to the lung and bone in 30% of patients. It is not possible to distinguish benign follicular adenomas from follicular carcinomas by FNA or frozen section compared to papillary carcinoma. If carcinoma is present, a total thyroidectomy and iodine-131 scanning is generally performed. Some surgeons may recommend removal of only one lobe if the cancer is small (< 1.5 cm) and isolated to one gland.
Medullary Carcinoma of the Thyroid (MCT)
This rare form of thyroid carcinoma is notable for its poor prognosis and association with several syndromes. MCT originates from what are called the parafollicular cells (C cells) of the thyroid. These cells make a hormone called calcitonin. MCT previously was diagnosed by measuring increased levels of this hormone in the blood. MCT can now be diagnosed at birth by blood samples demonstrating genetic abnormalities (the RET proto-oncogene on chromosome 10). MCT can run in families associated with certain syndromes: multiple endocrine neoplasia-MEN IIA, MEN IIB, and familial MCT. Family members can be screened by blood tests to determine who has the genetic abnormality. The thyroid gland can then be removed before cancer has a chance to develop and the outcome is significantly improved. Once cancer has developed, it quickly spreads to the lymph nodes and the chance for a cure is low.
Clinical Features of MCT
MCT occurs by itself in adolescence or at a much earlier age as part of the MEN syndromes. MEN IIA involves tumors of the thyroid (MCT), adrenal gland (pheochromocytoma), and the parathyroid glands (hyperparathyroidism). MEN IIB includes MCT, pheochromocytoma, marfanoid body features (tall, thin), and tumors of the nervous system (ganglioneuroma). MEN IIA is four times more common than MEN IIB, although both are rare. MCT is especially aggressive when associated with MEN IIB. Most children with MCT and MEN are female. Family members should be screened for the RET proto-oncogene.
Once the RET proto-oncogene is identified, total thyroidectomy is indicated. The lymph nodes in the middle of the neck are also removed to determine if the cancer has spread. With MEN IIB, thyroidectomy should be before 6 months of age, and before 5 years in patients with MEN IIA. In children with non-familial MCT, total thyroidectomy is also indicated. In this setting, if changes of MCT are seen throughout the gland, rather than one lobe, other family members should be examined. Cure rates are approximately 50% at 10 years. The prognosis is worse if the MCT has spread to the lymph nodes toward the sides of the neck.
Article and graphics adapted from O'Neill: Principles of Pediatric Surgery. © 2003, Elsevier.