Thyroid carcinoma: Clinical sciences

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Introduction0:00–0:42

Thyroid carcinoma is a malignant degeneration of either follicular or C-cells of the thyroid. The vast majority of thyroid cancers are differentiated tumors, including papillary, follicular, and oncocytic carcinoma, formerly known as Hurthle cell carcinoma.
These differentiated tumors carry a good prognosis. Medullary carcinoma of the C-cells, which produce calcitonin, is more aggressive, while undifferentiated tumors called anaplastic carcinoma have the worst prognosis.Let’s talk about the first steps to assessing a patient.

History and physical examination0:42–2:47

When assessing a patient with chief concern suggesting thyroid carcinoma, your first step is to obtain a focused history and physical exam.
Your patient could be asymptomatic, and in fact might be presenting because a thyroid mass was found incidentally on a physical exam or on imaging done for another reason.
If your patient is symptomatic, symptoms may include hoarseness or difficulty swallowing, especially if there's a mass effect from the tumor compressing the recurrent laryngeal nerve or the esophagus.
In some cases, the tumor can even compress on the trachea, leading to stridor. You should also ask your patient about risk factors that increase the likelihood of thyroid carcinoma.
These include biological sex, as it’s more likely to occur in women, but aggressive tumors are more likely to occur in men.
Thyroid carcinoma also presents in a bimodal age distribution, often in patients who are younger than 20 or older than 60 years.
Finally, papillary thyroid cancer is associated with childhood neck irradiation.Physical exam typically demonstrates a painless neck mass that might be firm, fixed, and asymmetric in shape.
You should also examine the neck for lymph nodes, as they help later with cancer staging. Alright, your next step is to assess thyroid function with a TSH.
If the TSH is below reference range, the patient has hyperthyroidism, and you should consider an alternative diagnosis. If the TSH is normal or above reference range, then your patient is euthyroid or hypothyroid, respectively.
You should suspect a malignancy in these cases. Your next step is to obtain a thyroid ultrasound.
Alright, so these ultrasound results will be your first clue. If ultrasound shows a small, cystic lesion that’s smaller than 1 cm, this is not consistent with malignancy, so consider an alternative diagnosis.On the other hand, if ultrasound demonstrates a solid lesion that’s larger than 1 cm with microcalcifications, hypervascularity, or irregular margins, then you should suspect thyroid carcinoma.

High-risk patients2:47–3:46

Your next step is to obtain either an ultrasound-guided fine needle aspiration or FNA for short, or a core needle biopsy.
You will use the biopsy results to determine next steps.First, if there are no malignant cells, then you should consider an alternative diagnosis.
On the other hand, if the initial biopsy shows malignant cells, you’ll want to use the histology results to distinguish between types of malignancies.Now, let’s take a look at the different types of malignancies.

Papillary Carcinoma3:46–5:07

Now, let’s first consider papillary carcinoma. This one is characterized by papillae lined by epithelial cells with Orphan Annie-Eye nuclei, which look like pale, empty nuclei, or intranuclear pseudoinclusions, which look like bubbles, and are actually invaginations of the cytoplasm into the nucleus .
In addition, you may find psammoma bodies, which are abnormal calcium deposits within the stroma.You’ll then want to stage the cancer using the TNM staging system and a CT scan to determine if the tumor can be resected.
This stands for Tumor size and location, lymph Node in volvement, and presence of distant Metastasis. The treatment for papillary thyroid carcinoma is surgical resection.
The surgeon will determine if a lobectomy or total thyroidectomy with lymph node dissection is required. Patients who get total thyroidectomy also require postoperative thyroid hormone replacement.
If there’s metastatic disease, the patient may need radioactive iodine, radiation, or targeted systemic therapy.Alright, let’s go back to the FNA results and discuss follicular carcinoma next.

Follicular Carcinoma 5:07–5:43

This cancer is characterized by epithelial cells in a follicular pattern. As before, you’ll want a CT to assist with TNM staging.
Treatment primarily consists of surgical resection. A lobectomy with an intraoperative frozen section is usually performed first.
If there’s evidence of capsular invasion, the rest of the thyroid is removed. These patients would also need postoperative thyroid hormone replacement.

Oncocytic Carcinoma5:43–7:12

Okay, let’s talk about the findings in oncocytic carcinoma. This malignancy is characterized by pink oncocytic epithelial cells with large amounts of granular acidophilic cytoplasm, arranged in a follicular or solid pattern.
Oncocytic carcinoma is managed similarly to follicular carcinoma, first by TNM staging guided by CT, and then treated with surgical resection and postoperative thyroid hormone replacement if needed.
Here’s a high yield fact! Papillary, follicular, and oncocytic carcinoma are considered differentiated thyroid cancers.
These are the only thyroid cancers where age is considered as part of the staging system. Patients younger than 55 years are staged based on the presence of metastases.
If the patient has no evidence of metastasis, they are stage I; if they have distant metastasis, they are stage II. On the other hand, patients older than 55 years are staged using standard TNM staging.
Differentiated thyroid cancers may also be treated with radioactive iodine therapy depending on the risk of disease persistence or recurrence, with those with positive lymph nodes, residual disease, or distant metastases qualifying for the therapy.

Medullary Carcinoma7:12–10:20

Next up we have medullary carcinoma. This one is characterized by sheets of round, oval or spindle shaped neoplastic cells that originate from parafollicular C-cells.
You’ll also see amyloid stroma that stains positive with Congo red staining.Here’s a high-yield fact! Once you’ve diagnosed medullary carcinoma, you’ll want to order calcitonin and carcinoembryonic antigen or CEA, as they can predict progression and aggressiveness of metastatic medullary carcinoma.
Okay, once you’ve diagnosed medullary carcinoma, your next step is to assess for a RET germline mutation. If there is no RET mutation, you can proceed with TNM staging using a CT, and then treat with surgical resection of the thyroid, and postoperative thyroid hormone replacement.
Now, let’s go back and discuss when a RET germline mutation exists, or when results are inconclusive and the status of the mutation remains uncertain.
In these cases, there’s a higher likelihood of associated endocrine carcinomas. So, you’ll need to evaluate for hyperparathyroidism, which can be a result of parathyroid carcinoma; and evaluate for pheochromocytoma.
Serum calcium is used to look for hyperparathyroidism; while plasma metanephrines are used to detect pheochromocytoma. If these labs are within reference range, there’s no hyperparathyroidism or pheochromocytoma.
You can proceed with TNM staging using a CT, and then treat with surgical resection of the thyroid and postoperative thyroid hormone replacement.
Now, let’s say the serum calcium is elevated, meaning the patient has hyperparathyroidism; or the plasma metanephrines are above reference range, meaning the patient has pheochromocytoma.
In these cases, you’ll still proceed with TNM staging using a CT, and then treat with surgical resection of the thyroid and postoperative thyroid hormone replacement.
However, you’ll also need to consider resection of the parathyroid glands with subsequent parathyroid hormone replacement; or an adrenalectomy.Here’s a high-yield fact!
Medullary thyroid cancers can be associated with several syndromes, such as Cowden syndrome, familial adenomatous polyposis or FAP, and cancers with BRAF gene mutations, as well as multiple endocrine neoplasia or MEN 2 syndrome.
This one comes in two flavors: MEN 2A and B. Both types predispose to the development of pheochromocytoma.
In addition, MEN 2A also predisposes to parathyroid hyperplasia or adenoma, while patients with MEN 2B can also present with mucosal neuromas and a Marfanoid body habitus.
Alright, let’s go back to FNA and talk about the most aggressive diagnosis, anaplastic carcinoma. If you see a pattern of ovoid or spindle-shaped epithelial cells on microscopy with giant, irregular nuclei, increased mitotic activity, and extensive lymphovascular invasion, you can make your diagnosis of anaplastic thyroid carcinoma.

Anaplastic Carcinoma 10:20–12:19

Your next step is to further evaluate for airway or vocal cord compromise with a laryngoscopy. In addition, order labs to help determine medical treatment options, including a CBC for cell lineage abnormalities; a CMP for liver or kidney involvement; a serum thyroglobulin for coexisting differentiated thyroid cancer; and molecular testing, like BRAF V600E mutations.
Lastly for TNM staging, obtain a CT of the head, neck, chest, abdomen, and pelvis. Here’s a high-yield fact!
Anaplastic thyroid carcinoma is so aggressive, it’s only considered stage IV, but is divided into three substages. Stages IVa and IVb include localized cancer that hasn’t metastasized, while stage IVc has distant metastases.
Because anaplastic carcinomas are so aggressive, the treatment is also aggressive. The surgeon will help determine whether surgical resection is feasible.
Keep in mind, some patients will need surgical resection to help debulk the tumor and prevent airway obstruction. Most patients will also need chemotherapy and radiation, whether or not they undergo surgical resection.
Some patients, depending on their molecular analysis, will also qualify for targeted therapy with oncogenic inhibitors. Finally, consider palliative care involvement to improve quality of life and support end of life decisions.
Alright, as a quick recap… If you suspect thyroid carcinoma, your first step is to determine whether or not the patient is euthyroid or hypothyroid.

Review12:19–13:07

If so, you’ll use a thyroid ultrasound to determine suspicion for malignancy. If you suspect malignancy based on ultrasound results, you’ll then want to obtain a FNA or core needle biopsy to assess histology.
This will help you distinguish between papillary, follicular, oncocytic, medullary, or anaplastic carcinoma. All types of carcinoma will require surgical resection; patients who have total thyroidectomy will also require postoperative thyroid hormone replacement.
Lastly, more aggressive forms may require chemotherapy,
Thyroid carcinoma: Video, Causes, and Symptoms | Osmosis