USMLE® Step 1 style questions USMLE
A 60-year-old woman comes to the office due to a neck lump. The patient reports no symptoms, weight loss, dysphagia, or voice changes. She does not use tobacco, excessive alcohol, or illicit substances. Temperature is 37.0°C (98.6°F), pulse is 70/min, and blood pressure is 125/80 mmHg. On physical examination, there is a fixed non-tender nodule in the left thyroid lobe. Serum TSH is within normal limits, and ultrasound shows a 2.5 cm solid mass. A fine-needle biopsy is obtained and shows varying degrees of follicles and microfollicles. A decision is made to perform thyroid lobectomy. Which of the following pathohistological findings will confirm the diagnosis of follicular thyroid cancer?
Normally, the hypothalamus, which is located at the base of the brain, secretes 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 gland 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 into T3, and it can exert its effect. T3 speeds up the basal metabolic rate.
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 thyroid is also made up of parafollicular or C cells, which are near the follicles.
DNA mutations can cause thyroid cells to become cancerous.
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 and that slow down cell division or make cells die if they divide uncontrollably.
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.
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 are psammoma bodies, which are calcium deposits within the papillae.
This type of thyroid cancer is more frequent 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 can invade into 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.
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