Thyroid nodules and thyroid cancer: Pathology review

On the endocrinology ward, two individuals came in.

Both individuals complained about feeling a lump on their necks, but reports no other symptoms.

The first one is 49 year old Dasha who as a child, lived close to Chernobyl.

The other one is 27 year old Mike, who’s family history involves multiple endocrine neoplasia type 2A.

On exam, they each had a painless mass on their thyroid.

Both people had normal T3, T4, and TSH levels.

They underwent thyroid echography, which showed cold nodules.

Afterwards, fine-needle biopsies were done.

Both individuals had tumors on their thyroids.

First, let’s refresh some info on the thyroid.

The thyroid gland is an endocrine gland located in the neck.

The thyroid gland is made up of thousands of follicles, which are small spheres lined with follicular cells.

Follicular cells convert thyroglobulin, a protein found in follicles, into two iodine-containing hormones, tri-iodo-thyronine or T3, and thyroxine or T4.

Once released from the thyroid gland, these hormones enter the blood and bind to circulating plasma proteins.

Once inside the cell T­4 is mostly converted into T3, at which point it can exert its effect.

T3, among other effects, speeds up the basal metabolic rate, increases cardiac output, stimulates bone resorption and activates the sympathetic nervous system.

The thyroid is 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.

Calcitonin also inhibits renal tubular cell reabsorption of calcium, allowing the calcium to be excreted in the urine.

Now, DNA mutations can cause thyroid cells to become cancerous.

For example, a mutation might change a 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, like TP53, 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.