Encapsulated angioinvasive follicular thyroid carcinoma

by Jason Wasserman MD PhD FRCPC
January 8, 2025

Encapsulated angioinvasive follicular thyroid carcinoma is a type of thyroid cancer that originates from the follicular cells of the thyroid gland. It is called “encapsulated” because it is separated from the normal thyroid gland by a thin band of tissue called a tumour capsule and “angioinvasive” because, upon microscopic examination, cancer cells were found inside at least one blood vessel outside the tumour.

What are the symptoms of encapsulated angioinvasion follicular thyroid carcinoma?

Symptoms of encapsulated angioinvasive follicular thyroid carcinoma may include:

• A lump or swelling in your neck that you can see or feel.
• Voice changes, like hoarseness.
• Trouble with swallowing or breathing.

What causes encapsulated angioinvasion follicular thyroid carcinoma?

The exact cause of encapsulated angioinvasion follicular thyroid carcinoma is not well understood, but several risk factors and genetic mutations have been identified:

1. Radiation exposure: Previous exposure to radiation, especially during childhood, increases the risk.
2. Iodine deficiency: Regions with low dietary iodine intake have higher incidences of follicular thyroid carcinoma.
3. Genetic mutations: Follicular thyroid carcinoma is associated with gene mutations such as RAS, PAX8-PPARγ, and the TERT promoter.

How is this diagnosis made?

The diagnosis of encapsulated angioinvasive follicular thyroid carcinoma involves several steps:

1. Physical examination: Evaluation of the neck for lumps or nodules.
2. Ultrasound: Imaging to assess the thyroid and surrounding structures, providing details about the nodule’s size, composition, and vascularity.
3. 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.
4. Thyroid function tests: Blood tests to measure levels of thyroid hormones and thyroid-stimulating hormone (TSH).
5. Surgical removal of the nodule: Surgery is often required to make the final diagnosis of encapsulated angioinvasive follicular thyroid carcinoma. This usually involves removing half of the thyroid gland. The nodule is then sent to a pathologist for histopathological examination, which is necessary to assess for capsular and vascular invasion.

Microscopic features of encapsulated angioinvasive follicular thyroid carcinoma

Microscopically, encapsulated angioinvasive 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. This diagnosis is made when tumour cells invade blood vessels within or beyond the tumour’s capsule. This invasion is carefully evaluated under the microscope using specific criteria.

What counts as vascular invasion?

Vascular invasion is confirmed when tumour cells are found inside a blood vessel, attached to its wall, mixed with fibrin (a protein involved in clotting), or covered by the vessel’s lining (endothelium). In some cases, the tumour grows directly into the vessel, appearing as a polyp-like structure inside.

What does not count as vascular invasion?

Not all tumour involvement near blood vessels qualifies as vascular invasion. For example, tumour cells pressing against a blood vessel without entering it are not considered vascular invasion. Similarly, tumour cells floating freely in a vessel without being attached to the wall or covered by endothelium do not meet the criteria. Changes in blood vessels caused by prior procedures, such as fine-needle aspiration, can also mimic vascular invasion but are not diagnostic.

Type of vessels involved

Vascular invasion typically involves veins, not lymphatic vessels, which aligns with the observation that encapsulated angioinvasive follicular thyroid carcinoma rarely spreads to lymph nodes.

Number of blood vessels involved

The number of blood vessels involved by tumour cells, referred to as “foci” (plural of “focus,” meaning a single area of invasion), is a key factor in determining how the tumour might behave. Tumours with fewer than four foci of vascular invasion tend to have a better prognosis. This means that when only a small number of blood vessels are affected, the tumour is less likely to spread to distant body parts. In contrast, tumours with four or more foci of vascular invasion are associated with a higher risk of distant spread and a poorer outcome.

Pathologists carefully count the foci of vascular invasion. Each focus is a separate area where tumour cells have invaded a blood vessel, and these foci may be in different vessels near or within the tumour.

Why vascular invasion matters

The presence and extent of vascular invasion are important because they help determine the tumour’s potential to spread to other body parts. Tumours with more extensive vascular invasion (four or more foci) are more likely to spread, leading to a poorer prognosis. On the other hand, tumours with limited vascular invasion (fewer than four foci) tend to behave less aggressively.

Additional techniques for confirmation

Pathologists may use special tests, such as immunohistochemistry for markers like ERG or CD31, to highlight the blood vessel lining and confirm vascular invasion.

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 4.0 cm. Tumour size is important for encapsulated angioinvasive follicular thyroid carcinoma because it determines the pathologic tumour stage (pT). 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 is only visible under a microscope and indicates that the cancer has spread just beyond the thyroid capsule. It cannot be seen with the naked eye and 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.

Lymphatic invasion

Lymphatic invasion in the context of encapsulated angioinvasive 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. Unlike vascular invasion, 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 at the tissue’s cut edge. A positive margin, where tumour cells are found, suggests that some may remain in the body. In contrast, a negative margin, with no tumour cells at the edge, suggests that the tumour was entirely 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 through lymphatic vessels from a tumour to lymph nodes. 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 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 typically removed only if they are enlarged, and there is a high clinical suspicion that there may be cancer cells in them.

Neck dissections

A neck dissection is a surgical procedure to remove lymph nodes from the neck. The lymph nodes removed usually come from different neck areas, and each region 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.

How the lymph nodes will be described in your pathology report

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” indicates 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 outside of the lymph node and spread into the surrounding tissue.

Why is the examination of lymph nodes important?

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 encapsulated angioinvasive 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