The thyroid gland is an endocrine gland in the neck that produces thyroid hormones. If the cells of the thyroid gland start to divide uncontrollably, then that’s considered thyroid cancer. Normally, the hypothalamus, which is located at the base of the brain, secretes the thyrotropin-releasing hormone, or ΤRH, into the hypophyseal portal system – which is a network of capillaries linking the hypothalamus to the anterior pituitary. The anterior pituitary then releases a hormone of its own, called thyroid-stimulating hormone, thyrotropin, or simply TSH.
TSH stimulates the thyroid gland which is a gland located in the neck that looks like two thumbs hooked together in the shape of a “V”. The entire land is covered in a thin, tough membrane called the fibrous capsule. If we zoom into the thyroid gland, we’ll find thousands of follicles, which are small hollow spheres whose walls are lined with follicular cells and are separated by a small amount of connective tissue. Follicular cells convert thyroglobulin, a protein found in follicles,
Into two iodine-containing hormones, triiodothyronine or T3, and thyroxine or T4. Once released from the thyroid gland, these hormones enter the blood and bind to circulating plasma proteins. Only a small amount of T3 and T4 will travel unbound in the blood, and these two hormones get picked up by nearly every cell in the body. Once inside the cell T4 is mostly converted intoT3, at which point it can exert its effect. T3 speeds up the basal metabolic rate. So as an example, they might produce more proteins and burn up more energy in the form of sugars and fats.
It’s as if the cells are in a bit of frenzy. T3 increases cardiac output stimulates bone resorption – thinning out the bones, and activates the sympathetic nervous system, the part of the nervous system responsible for our ‘fight-or-flight’ response. Thyroid hormone is important – and the occasional increase is like getting a boost to fight off a zombie or to stay warm during a snowstorm! Thyroid hormones are also involved in a number of other things, like controlling sebaceous and sweat gland secretion.
Hair follicle growth, and regulating proteins and mucopolysaccharide synthesis by skin fibroblasts. The thyroiditis also made up of parafollicular or C cells, which are near the follicles. These cells produce calcitonin, a hormone that lowers blood calcium levels by inhibiting osteoclasts. Osteoclasts are bone cells that break down bone tissue which frees up the calcium to enter the bloodstream. Calcitonin also inhibits renal tubular cell reabsorption of calcium, allowing the calcium to be excreted in the urine. DNA mutations can cause thyroid cells to become cancerous.
For example, a mutation might change proto-oncogenes like RET and BRAF, which are genes that code for proteins that promote cell growth and proliferation, into oncogenes. That would mean that the proteins force the cell to be stuck in the “on” position, always dividing, and that causes the thyroid cell to turn into a tumor. There are other genes, called tumor suppressors, such as PTEN that normally slow down cell division or make cells die if they divide uncontrollably.
DNA mutations might also turn off tumor suppressor genes, which allows thyroid cells that try to divide uncontrollably to go unchecked. Over time, a thyroid cell that divides uncontrollably will lead to a lump of cells within the thyroid, called a nodule. Most often, nodules are non-functional, so they don’t produce thyroid hormones, and these are called “cold” nodules. Now, there are three main types of thyroid cancer: differentiated, medullary, and anaplastic.
In differentiated thyroid cancer, cancer arises from follicular cells, and it’s known as differentiated because the cancer cells look and act like normal thyroid cells. Within the differentiated thyroid cancers, there are three groups: papillary, follicular, and Hṻrthle cell carcinoma. The first group, papillary carcinomas, represents the most common form of thyroid cancer and is associated with RET and BRAF gene mutations as well as exposure to ionizing radiation during childhood, as seen in kids near the Chernobyl nuclear power plant accident.
The name “papillary” refers to the fact that these tumors have finger-like prolongations of follicle cells known as papillae that tend to grow slowly towards nearby lymphatic vessels and invade nearby lymph nodes in the neck. Under the microscope, the nuclei of papillary carcinomas cells contain very few proteins and a small amount of DNA, and that gives the appearance of an empty nucleus, sometimes called an “Orphan Annie eye” nucleus based on an old famous cartoon character. Another feature is psammoma bodies, which are calcium deposits within the papillae.
The second type, follicular carcinomas, also known as follicular adenocarcinomas, represent the second most common form of thyroid cancer. This type of thyroid cancer is more frequently associated with countries where people have low dietary iodine but is also with the activation of RAS oncogene or the deactivation of the tumor suppressor gene PTEN. In follicular carcinomas, the tumor develops from the follicular cells and grows until it breaks through the fibrous capsule.
From there, follicular carcinomas invade nearby blood vessels and spread to other parts of the body like the lungs, liver, bone, and brain, but interestingly they don’t typically invade nearby lymph nodes. The third type, Hṻrthle cell carcinoma, is a rare type of cancer and it’s considered a variant of follicular carcinoma. A tumor can often cause the immune cells to attack it, causing inflammation. Follicular cells in the thyroid become adapt to cellular stress like inflammation by becoming Hṻrthle cells.
They do so by increasing the production of mitochondria which fills up their cytoplasm and gives it a granular appearance and stains pink. These cells are also seen in disorders like Hashimoto’s thyroiditis where the thyroid is also inflamed. Like in follicular carcinomas, Hṻrthle cells form neoplastic tumors that break through the fibrous capsule and invade via the bloodstream. So moving beyond the differentiated thyroid cancers, there are the medullary thyroid carcinomas that arise from C-cells.
There’s a higher concentration of C-cells in the upper ⅓ of the thyroid medulla which is where these tumors usually arise. Most of the time, it forms because of a spontaneous mutation in the RET oncogene, and it’s usually a single carcinoma in one lobe of the thyroid. But sometimes it can arise as part of an inherited mutation like in familial medullary thyroid carcinoma, which runs in families, and in those cases, there can be multiple carcinomas across both lobes.
It can also be associated with a hereditary condition called multiple endocrine neoplasias (or MEN), type 2A and 2B. In these conditions, one or more of the endocrine glands like the thyroid gland, parathyroid gland, and adrenal gland develop tumors. Under the microscope, medullary thyroid carcinoma is made up of spindle-shaped cells, which are called that because they’re long and skinny – like a spindle that’s used to spin fibers into thread. C-Cells in the tumor makes excessive amounts of calcitonin which deposits between the C-Cells.
Calcitonin is a protein hormone, so as the calcitonin deposits, the resulting clumps of protein stick together and form fibrous deposits called amyloid around the C-cells. Tumors formed by C-cells can also release other hormones like serotonin and vasoactive intestinal peptide which can cause increased gastrointestinal motility. Finally, there are the anaplastic thyroid carcinomas. These are a rare form of thyroid cancer, named for having altered cells that don’t look anything like normal thyroid cells.
It may be that these tumors derive from an existing papillary or follicular cancer where the cells mutate even more and become unrecognizable. Under the microscope, anaplastic carcinomas typically contain spindle-shaped cells as well as pleomorphic giant cells which are enlarged cells that vary in shape. These cancers are the most aggressive compared to other thyroid cancers. They often grow beyond the fibrous capsule of the thyroid gland and invade nearby structures. Most often the first sign of thyroid cancer is a solitary painless nodule in the thyroid gland.
Typically, hard and immovable nodules are more likely to be tumors. If the tumor gets too big or invades the larynx or esophagus, it can cause hoarseness and trouble swallowing. Thyroid cancers are non-functional so they usually do not present with signs of hyper or hypothyroidism. In medullary thyroid carcinoma, the release of vasoactive intestinal peptide leads to diarrhea, and increased serotonin levels lead to flushing of the skin. The diagnosis of thyroid cancer often begins with imaging studies, like a thyroid ultrasound, which can help identify a thyroid nodule.
Calcitonin levels are usually elevated in medullary thyroid carcinomas. A radioiodine scan can also be useful, that’s where radioactive iodine is ingested and taken up by cells that make thyroid hormone. Usually, thyroid tumors don’t make thyroid hormone, so they’re“cold nodules”. The best way to be sure is to use fine-needle aspiration, where a thin needle is used to take small tissue samples from the thyroid nodule, to identify the type of tumor. The treatment of thyroid cancer depends on mostlyon the type of cancer and how it has spread.
Options include partial thyroidectomy where the affected part is removed or total thyroidectomy where the entire thyroid is removed, followed by thyroid hormone replacement. All right, as a quick recap, thyroid cancer is cancer that forms in the thyroid gland. And it arises from either follicular cells or C cells. There are three main types of thyroid cancer: differentiated, medullary, and anaplastic. All the differentiated types arise from follicular cells and the most common type is papillary carcinoma. Medullary carcinoma arises from the C-cells of the thyroid which produce calcitonin. Diagnosis usually begins with a thyroid ultrasound and it’s confirmed with a fine-needle aspiration. Treatment consists of a total or partial thyroidectomy.