Papillary thyroid carcinoma

by Jason Wasserman MD PhD FRCPC
February 21, 2024


Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer, accounting for approximately 80% of all thyroid cancer cases. The thyroid gland, a vital butterfly-shaped organ located in the front of the neck, plays an important role in regulating metabolic processes within the body. The term “papillary” in the name comes from the cancer cells’ appearance under a microscope; most tumours contain tiny, finger-like projections called papillae.

This article will help you understand your diagnosis and pathology report for papillary thyroid carcinoma.

What are the symptoms of papillary thyroid carcinoma?

Symptoms of papillary 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 papillary thyroid carcinoma?

What causes papillary thyroid carcinoma isn’t fully understood. However, it seems to involve a combination of both genetic changes and environmental risk factors such as exposure to ionizing radiation and dietary influences. This type of cancer is also much more common in young women.

How is the diagnosis of papillary thyroid carcinoma made?

Diagnosing papillary thyroid carcinoma usually starts with a visit to your doctor, who might feel your neck for any unusual lumps. If they find something suspicious, they might order an ultrasound, which uses sound waves to create a picture of your thyroid gland. This helps them see if there are nodules (lumps) that need a closer look.

The gold standard for diagnosing papillary thyroid carcinoma, however, is a fine needle aspiration biopsy (FNAB). This involves using a very thin needle to take a small sample of tissue from the nodule. The sample is then examined under a microscope to check for cancer cells. After the diagnosis is made, your doctor may recommend surgery to remove part or all of the thyroid gland.

Variants of papillary thyroid carcinoma

Not all papillary thyroid carcinomas are the same. In pathology, the term “variant” refers to subtypes of papillary thyroid carcinoma that differ in their appearance under the microscope, their behaviour, and sometimes, their response to treatment. Some variants grow very slowly and are less likely to spread, while others can be more aggressive.

Understanding the specific variant of papillary thyroid carcinoma a person has is crucial for several reasons. It helps doctors predict how the cancer might behave, choose the best treatment plan, and offer the most accurate information about prognosis. In essence, knowing the variant paints a clearer picture of what to expect and how to tackle it. The following sections provide an overview of the most common variants of papillary thyroid carcinoma.

Classic variant

The classic variant is the most common type of papillary thyroid carcinoma which is why it is also called the conventional variant. The tumour is made up of many finger-like projections of tissue called papillae. Tumour cells from this variant commonly spread to lymph nodes in the neck.

Infiltrative follicular variant

The infiltrative follicular variant is another common type of papillary thyroid carcinoma. The tumour cells in this variant grow in small circular groups called follicles which can look very similar to the normal follicles found in the thyroid gland. Unlike invasive encapsulated follicular variant papillary thyroid carcinoma, the infiltrative follicular variant is not surrounded by a thin layer of tissue called a tumour capsule.

Tall cell variant

The tall cell variant of papillary thyroid carcinoma is an aggressive tumour that commonly spreads outside of the thyroid gland and to lymph nodes. To make the diagnosis of the tall cell variant, the tumour cells should be at least 3 times taller than they are wide. This type of tumour is more common in older adults and is seen very rarely in children.

Hobnail variant

The hobnail variant of papillary thyroid carcinoma is an aggressive tumour that commonly spreads outside of the thyroid gland, to lymph nodes, and distant parts of the body such as the bones. The hobnail variant is made up of tumour cells that appear to hang off the surface of the papillae within the tumour.

Solid/trabecular variant

The solid/trabecular variant of papillary thyroid carcinoma is an aggressive tumour that is more likely to spread to distant parts of the body such as the lungs. The tumour cells in the solid/trabecular variant grow in large groups or long chains. Pathologists describe these patterns of growth as solid or trabecular.

Oncocytic variant

The tumour cells in the oncocytic variant of papillary thyroid carcinoma are called oncocytic because they are larger than normal cells and look bright pink when viewed under a microscope. The prognosis for the oncocytic variant of papillary thyroid carcinoma is similar to the classic variant.

Diffuse sclerosing variant

The diffuse sclerosing variant of papillary thyroid carcinoma is more common in children and young adults. It is likely to involve both sides (right and left lobes) of the thyroid unlike other types of tumours which often only involve one side. Compared to the classic variant, the tumour cells in the diffuse sclerosing variant are more likely to spread outside of the thyroid gland and to distant parts of the body.

Columnar variant

The columnar variant is a rare but aggressive type of papillary thyroid carcinoma that commonly spreads to lymph nodes and other parts of the body. The columnar variant is made up of tumour cells that are taller than they are wide and the cells overlap in a way that pathologists describe as “pseudostratified”.

Genetic changes associated with papillary thyroid carcinoma

Papillary thyroid carcinoma, like many cancers, often involves changes in the DNA of thyroid cells. These changes allow the cells to grow faster and under less control than normal cells.

Some of the common genetic changes associated with this type of cancer include:

  • BRAF mutations: The BRAF gene makes a protein that is part of a signalling pathway known as MAPK, which helps regulate cell growth and division. A mutation (change) in the BRAF gene, particularly the BRAF V600E mutation, results in an abnormal version of the BRAF protein that is always active. This constant activity signals thyroid cells to grow and divide uncontrollably, leading to cancer. BRAF mutations are one of the most common genetic changes seen in papillary thyroid carcinoma and are associated with more aggressive forms of the disease.
  • RET/PTC rearrangements: RET is a gene that codes for a type of receptor protein on the surface of cells, which is involved in cell growth signals. In papillary thyroid carcinoma, parts of the RET gene can become abnormally connected (rearranged) with parts of other genes, creating fusion genes called RET/PTC rearrangements. These rearrangements produce abnormal proteins that can activate signalling pathways like MAPK, even without the normal external signals that would typically start the process, leading to uncontrolled cell growth and cancer.
  • RAS mutations: RAS genes (KRAS, NRAS, HRAS) produce proteins that are important in regulating cell division, growth, and death. When mutated, RAS proteins can become permanently active, continuously telling cells to grow and divide. This unregulated cell growth can lead to the formation of tumours. RAS mutations are found in a variety of cancers, including some cases of papillary thyroid carcinoma, and can contribute to both the initiation and progression of the disease.

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 the tumour as being 4.0 cm. The size of the tumour is important for papillary thyroid carcinoma because it is used to determine the pathologic tumour stage (pT) and because larger tumours are more likely to spread to other parts of the body such as lymph nodes.

Multifocal tumours

​It is not unusual for more than one tumour to be found in the same thyroid gland. Multifocal is a word pathologists use to describe finding more than one tumour of the same type (variant) in the thyroid gland. If different types (variants) of papillary thyroid carcinoma are found, each tumour will be described separately in your report. When more than one tumour is found, only the largest tumour is used to determine the pathologic tumour stage (pT).​

Extrathyroidal extension

​Extrathyroidal extension means that tumour cells have spread outside of the thyroid gland and into the surrounding tissues. Pathologists divide extrathyroidal extension into two types:

  • Microscopic extrathyroidal extension – The tumour cells outside of the thyroid gland could be seen only after the tumour was examined under the microscope. This type of extrathyroidal extension is not associated with a worse prognosis and it does not change the pathologic tumour stage (pT).
  • Gross (macroscopic) extrathyroidal extension – The tumour could be seen spreading into surrounding tissues without the use of a microscope. This type of extrathyroidal extension may be seen by your doctor at the time of surgery or by the pathologist’s assistant performing the gross examination of the tissue sent to pathology. This type of extrathyroidal extension is important because these tumours are more likely to spread to other parts of the body. Gross extrathyroidal extension also increases the pathologic tumour stage (pT) to pT3b.

Vascular invasion (angioinvasion)

Vascular invasion, also known as angioinvasion, is the spread of tumour cells into a blood vessel. When tumour cells invade blood vessels, they have the potential to travel through the bloodstream to other parts of the body, a process known as metastasis. For this reason, vascular invasion is important because it indicates a more aggressive form of cancer. Most reports will describe vascular invasion as negative if no tumour cells are seen inside a blood vessel or positive if tumour cells are seen inside at least one blood vessel.

Lymphatic invasion

​Lymphatic invasion means that tumour cells are seen inside lymphatic channels, small hollow tubes that allow the flow of a fluid called lymph from tissues to immune organs called lymph nodes. Lymphatic invasion is important because it increases the risk that tumour cells will spread through the lymphatic system to lymph nodes. If lymphatic invasion is seen, it will be called positive. If no lymphatic invasion is seen, it will be called negative.

Margins

​In pathology, a margin refers to 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.

Margin

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 a metastasis.

Lymph node

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 areas of the neck 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 were removed from your body, they will be examined under the microscope by a pathologist and the results of this examination 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.

extranodal extension

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 papillary 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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