by Jason Wasserman MD PhD FRCPC
July 26, 2024
Background:
Follicular thyroid carcinoma (FTC) is a type of thyroid cancer that originates from the follicular cells of the thyroid gland. These cells are responsible for producing and secreting thyroid hormones. Follicular thyroid carcinoma is the second most common type of thyroid cancer, following papillary thyroid carcinoma. It typically affects middle-aged adults and has a slightly higher prevalence in women.
What are the symptoms of follicular thyroid carcinoma?
The symptoms of follicular thyroid carcinoma can be subtle in the early stages and may include:
- A palpable nodule or lump in the neck.
- Swelling in the neck.
- Hoarseness or changes in voice.
- Difficulty swallowing.
- Difficulty breathing.
- Persistent cough not related to a cold.
What causes follicular thyroid carcinoma?
The exact cause of follicular thyroid carcinoma is not well understood, but several risk factors and genetic mutations have been identified:
- Radiation exposure: Previous exposure to radiation, especially during childhood, increases the risk.
- Iodine deficiency: Regions with low dietary iodine intake have higher incidences of follicular thyroid carcinoma.
- Genetic mutations: Mutations in genes such as RAS, PAX8-PPARγ, and TERT promoter are associated with follicular thyroid carcinoma.
How is the diagnosis of follicular thyroid carcinoma made?
The diagnosis of follicular thyroid carcinoma involves several steps:
- Physical examination: Evaluation of the neck for lumps or nodules.
- Ultrasound: Imaging to assess the thyroid and surrounding structures, providing details about the nodule’s size, composition, and vascularity.
- Fine-needle aspiration (FNA) biopsy: A sample of cells is taken from the nodule and examined under a microscope. However, FNA cannot definitively distinguish between benign and malignant follicular tumours.
- Thyroid function tests: Blood tests to measure levels of thyroid hormones and thyroid-stimulating hormone (TSH).
- Surgical to remove the nodule: Surgery is often required to make the final diagnosis of follicular thyroid carcinoma. This often involves removing the half of the thyroid gland. The nodule is then sent to a pathologist for histopathological examination. This is necessary to assess for capsular and vascular invasion.
Microscopic features of follicular thyroid carcinoma
Microscopically, follicular thyroid carcinoma is characterized by tumour cells arranged in follicular patterns resembling normal thyroid follicles. These cells are uniform, small to medium-sized with round to oval nuclei and have abundant colloid. A critical feature for diagnosis is capsular invasion, where tumour cells penetrate the fibrous capsule surrounding the nodule. Vascular invasion, where tumour cells invade blood vessels within or beyond the capsule, is also an important diagnostic criterion.
Capsular invasion
Most follicular thyroid carcinomas are surrounded by a layer of fibrous tissue called a tumour capsule. Capsular invasion refers to the penetration of this fibrous capsule by tumour cells. This invasion is a critical feature distinguishing follicular thyroid carcinoma from benign follicular adenoma.
Subtypes of follicular thyroid carcinoma
After microscopic examination, follicular thyroid carcinoma can be categorized into different subtypes:
- Minimally invasive follicular thyroid carcinoma.
- Widely invasive follicular thyroid carcinoma.
- Encapsulated angioinvasive follicular thyroid carcinoma.
These subtypes are described in greater detail in the sections below.
Minimally invasive follicular thyroid carcinoma
In minimally invasive follicular thyroid carcinoma, the tumour is surrounded by a fibrous tumour capsule. However, microscopic examination shows tumour cells breaking through the capsule and spreading into the surrounding thyroid gland tissue. This subtype is usually associated with a better prognosis and a lower risk of metastasis compared to encapsulated angioinvasive and widely invasive follicular thyroid carcinoma.
Widely invasive follicular thyroid carcinoma
Widely invasive follicular thyroid carcinoma exhibits extensive invasion into the surrounding thyroid tissue and may or may not show vascular invasion. This subtype is more aggressive and has a higher risk of distant metastasis and recurrence compared to minimally invasive follicular thyroid carcinoma.
Encapsulated angioinvasive follicular thyroid carcinoma
Encapsulated angioinvasive follicular thyroid carcinoma is characterized by a well-defined capsule and vascular invasion without significant capsular invasion. This subtype falls between minimally invasive and widely invasive follicular thyroid carcinoma in terms of aggressiveness and prognosis.
Tumour size
After the tumour is removed completely, it will be measured. The tumour is usually measured in three dimensions, but only the largest dimension is described in your report. For example, if the tumour measures 4.0 cm by 2.0 cm by 1.5 cm, your report will describe it as being 4.0 cm. Tumour size is important for follicular thyroid carcinoma because it determines the pathologic tumour stage (pT) and because larger tumours are more likely to spread to other body parts, such as lymph nodes.
Extrathyroidal extension
Extrathyroidal extension (ETE) refers to the spread of cancer cells beyond the thyroid gland into surrounding tissues. It is an important prognostic factor in thyroid cancer, as it can significantly influence both the staging and management of the disease.
Extrathyroidal extension is classified into two types based on the extent of the spread:
- Microscopic extrathyroidal extension: This form of extension is only visible under a microscope and indicates that the cancer has spread just beyond the thyroid capsule but cannot be seen with the naked eye. It may involve minimal infiltration into surrounding soft tissues.
- Macroscopic (or gross) extrathyroidal extension: This type is visible to the naked eye or detectable during surgery. It involves more obvious and extensive invasion into neighbouring structures such as muscles, trachea, esophagus, or major blood vessels.
Extrathyroidal extension is important for the following reasons:
- Prognosis: Macroscopic (gross) extrathyroidal extension is associated with a worse prognosis. It suggests a more aggressive cancer that is more likely to recur and metastasize.
- Staging: Extrathyroidal extension impacts the staging of thyroid cancer. For instance, in the TNM (Tumor, Node, Metastasis) classification system used for thyroid cancer, macroscopic extrathyroidal extension results in a higher pathologic tumour stage (pT).
- Treatment and follow-up: The presence of macroscopic (gross) extrathyroidal extension might lead to more aggressive treatment strategies and closer follow-up to reduce the risk of recurrence.
Vascular invasion (angioinvasion)
Vascular invasion, or angioinvasion, in the context of follicular thyroid carcinoma, means that the cancer cells have spread into the blood vessels in or around the tumour. This is an important sign because it can indicate that the cancer might spread to other body parts, such as the lungs or bones.
Pathologists use two terms to describe how much vascular invasion (angioinvasion) is present:
- Focal vascular invasion (angioinvasion): This means cancer cells are found in less than 4 blood vessels.
- Extensive vascular invasion (angioinvasion): This means cancer cells are found in 4 or more blood vessels.
Extensive vascular invasion (4 or more blood vessels) usually means a higher risk of the cancer spreading, which can lead to a worse prognosis. If there is extensive angioinvasion, doctors often recommend more aggressive treatments to try to control the cancer better. This could include additional surgery, radioactive iodine therapy, or more frequent follow-up visits to monitor for any signs of cancer spreading.
Lymphatic invasion
Lymphatic invasion in the context of follicular thyroid carcinoma of the thyroid gland refers to the infiltration and spread of cancer cells into the lymphatic system. Cancer cells that enter the lymphatic system can travel to lymph nodes. It is relatively uncommon to find lymphatic invasion with follicular thyroid carcinoma, and unlike vascular invasion, the presence of lymphatic invasion is not necessarily associated with a more aggressive disease or a worse prognosis.
Margins
In pathology, a margin is the edge of tissue removed during tumour surgery. The margin status in a pathology report is important as it indicates whether the entire tumour was removed or if some was left behind. This information helps determine the need for further treatment.
Pathologists examine margins to check if tumour cells are present at the tissue’s cut edge. A positive margin, where tumour cells are found, suggests that some tumour cells may remain in the body. In contrast, a negative margin, with no tumour cells at the edge, suggests the tumour was fully removed. Some reports also measure the distance between the nearest tumour cells and the margin, even if all margins are negative.
Lymph nodes
Lymph nodes are small immune organs found throughout the body. Cancer cells can spread from a tumour to lymph nodes through small lymphatic vessels. For this reason, lymph nodes are commonly removed and examined under a microscope to look for cancer cells. The movement of cancer cells from the tumour to another part of the body, such as a lymph node, is called metastasis.
Cancer cells typically spread first to lymph nodes close to the tumour, although lymph nodes far away from the tumour can also be involved. For this reason, the first lymph nodes removed are usually close to the tumour. Lymph nodes further away from the tumour are only typically removed if they are enlarged and there is a high clinical suspicion that there may be cancer cells in the lymph node.
A neck dissection is a surgical procedure performed to remove lymph nodes from the neck. The lymph nodes removed usually come from different neck areas, and each area is called a level. The levels in the neck include 1, 2, 3, 4, and 5. Your pathology report will often describe how many lymph nodes were seen in each level sent for examination. Lymph nodes on the same side as the tumour are called ipsilateral, while those on the opposite side of the tumour are called contralateral.
If any lymph nodes are removed from your body, they will be examined under the microscope by a pathologist, and the examination results will be described in your report. “Positive” means that cancer cells were found in the lymph node. “Negative” means that no cancer cells were found. If cancer cells are found in a lymph node, the size of the largest group of cancer cells (often described as “focus” or “deposit”) may also be included in your report. Extranodal extension means that the tumour cells have broken through the capsule on the outside of the lymph node and have spread into the surrounding tissue.
The examination of lymph nodes is important for two reasons. First, this information determines the pathologic nodal stage (pN). Second, finding cancer cells in a lymph node increases the risk that cancer cells will be found in other parts of the body in the future. As a result, your doctor will use this information when deciding if additional treatment, such as radioactive iodine, chemotherapy, radiation therapy, or immunotherapy, is required.
Pathologic stage (pTNM)
The pathologic stage for follicular thyroid carcinoma can only be determined after the entire tumour has been surgically removed and examined under the microscope by a pathologist. The stage is divided into three parts: tumour stage (pT) which describes the tumour, nodal stage (pN) which describes any lymph nodes examined, and metastatic stage (pM) which describes tumour cells that have spread to other parts of the body. Most pathology reports will include information about the tumour and nodal stages. The overall pathologic stage is important because it helps your doctor determine the best treatment plan and predict the outlook for recovery.
Tumour stage (pT)
- T0: No evidence of primary tumour.
- T1: The tumour is 2 cm (about 0.8 inches) or smaller in its greatest dimension and confined to the thyroid.
- T1a: The tumour is 1 cm (about 0.4 inches) or smaller.
- T1b: The tumour is larger than 1 cm but not larger than 2 cm.
- T2: The tumour is larger than 2 cm but not larger than 4 cm (about 1.6 inches) and is still inside the thyroid.
- T3: The tumour is larger than 4 cm or has minimal extension beyond the thyroid gland.
- T3a: The tumour is larger than 4 cm but is still confined to the thyroid.
- T3b: The tumour shows gross extrathyroidal extension (it has spread into the muscles outside of the thyroid).
- T4: This indicates advanced disease.
- T4a: The tumour extends beyond the thyroid capsule to invade subcutaneous soft tissues, the larynx (voice box), trachea (windpipe), esophagus (food pipe), or recurrent laryngeal nerve (a nerve that controls the voice box).
- T4b: The tumour invades prevertebral space (area in front of the spinal column), and encases the carotid artery or the mediastinal vessels (major blood vessels).
Nodal stage (pN)
- N0: No regional lymph node metastasis (the cancer hasn’t spread to nearby lymph nodes).
- N1: There is metastasis to regional lymph nodes (near the thyroid).
- N1a: Metastasis is limited to lymph nodes around the thyroid (pretracheal, paratracheal, prelaryngeal/Delphian, and/or perithyroidal lymph nodes).
- N1b: Metastasis to other cervical (neck) or superior mediastinal lymph nodes (lymph nodes in the upper chest).
Other helpful resources
American Thyroid Association (ATA)
American Cancer Society
Learn more pathology
Atlas of Pathology
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