by Jason Wasserman MD PhD FRCPC
April 25, 2023
Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer in adults. PTC develops from specialized follicular cells normally found in the thyroid gland.
The first diagnosis of PTC is usually made after a procedure called a fine-needle aspiration biopsy (FNAB) is performed on a suspicious lump or nodule in the thyroid gland. After the diagnosis, part or all of the thyroid gland is usually removed and the tissue is sent to a pathologist for examination under the microscope.
In order to make the diagnosis of PTC, your pathologist must first see changes to a part of the cell called the nucleus. The nucleus is important because it holds most of the cell’s genetic material (DNA). The genetic material inside the cell is called chromatin. The nucleus is surrounded by a thin border called the nuclear membrane.
In a normal, healthy follicular cell, the nucleus is small and round, the nuclear membrane is smooth, and the chromatin fills the entire nucleus. In a PTC tumour cell, the nucleus is larger than normal, the membrane is bumpy, and the nucleus looks clear because the chromatin has been pushed to the side. The follicular cells are also larger than normal and they look crowded compared to the cells in a normal, healthy thyroid follicle. Pathologists call this group of changes “nuclear features of papillary thyroid carcinoma” and at least some of them must be seen in order to make the diagnosis.
PTC is divided into groups called variants based on how the tumour looks when examined under the microscope. The most common variants of PTC are classic, infiltrative follicular, tall cell, oncocytic, columnar, hobnail, solid/trabecular, and diffuse sclerosing. A tumour can be made up of only one variant or a combination of variants. If more than one variant is found in your tumour, your pathologist may say what percentage of the tumour is made up of each variant. The variant of PTC is important because some variants such as tall cell, hobnail, and columnar are more likely to spread to other parts of the body and are associated with a worse overall prognosis.
This is the most common type of PTC 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.
The tumour cells in the infiltrative follicular 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.
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. The tall cell variant is an aggressive tumour that commonly spreads outside of the thyroid gland and to lymph nodes.
The hobnail variant of PTC is made up of tumour cells that appear to hang off the surface of the papillae within the tumour. The hobnail variant 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 tumour cells in the solid/trabecular variant of PTC grow in large groups or long chains. Pathologists describe these patterns of growth as solid or trabecular. Compared to the classic variant, the tumour cells in the solid/trabecular variant are more likely to spread to distant parts of the body such as the lungs.
The tumour cells in the oncocytic variant of PTC 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.
The diffuse sclerosing variant 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.
The columnar variant of PTC 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”. 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.
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 PTC because it is used to determine the pathologic stage and because larger tumours are more likely to spread to other parts of the body such as lymph nodes.
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 PTC 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) (see Pathologic stage below).
Extrathyroidal extension is the movement of tumour cells out of the thyroid gland and into the surrounding tissues. Tumour cells that move far enough out of the thyroid gland may come into contact with additional structures such as muscles, the esophagus, or the trachea.
There are two types of extrathyroidal extension:
Macroscopic (gross) extrathyroidal extension is important because it increases the tumour stage (see Pathologic stage below) and is associated with a worse prognosis. In contrast, microscopic extrathyroidal extension does not change the tumour stage.
Vascular invasion (also called angioinvasion) is the spread of tumour cells into a blood vessel. Blood vessels carry blood around the body. Tumour cells that enter a blood vessel are able to spread to distant parts of the body such as the lungs and bones.
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. Vascular invasion is important because tumour cells that enter a blood vessel are more likely to spread to other parts of the body.
Lymphatic invasion means that tumour cells were seen inside a lymphatic vessel. Lymphatic vessels are 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 tumour cells can use lymphatic vessels to spread to other parts of the body such as lymph nodes or the lungs. If lymphatic invasion is seen, it will be called positive. If no lymphatic invasion is seen, it will be called negative.
A margin is the tissue that has to be cut by the surgeon to remove the tumour along with any normal tissue from your body. Pathologists examine all margins to see if there are any tumour cells at the cut edge of the tissue. A margin is considered positive when there are tumour cells at the very edge of the cut tissue. A negative margin means there were no tumour cells seen at the cut edge of the tissue. Margins can only be assessed after the entire tumour has been removed.
Lymph nodes are small immune organs located throughout the body. Cancer cells can travel from the thyroid to a lymph node through lymphatic channels located in and around the tumour (see Lymphatic invasion above). The movement of cancer cells from the thyroid to a lymph node is called metastasis. The risk of lymph node metastasis depends on the variant of PTC.
Your pathologist will carefully examine each lymph node for cancer cells. Lymph nodes that contain cancer cells are often called positive while those that do not contain any cancer cells are called negative. Most reports include the total number of lymph nodes examined and the number, if any, that contain cancer cells.
Lymph nodes from the neck are sometimes removed at the same time as the thyroid in a procedure called a neck dissection. The lymph nodes removed usually come from different areas of the neck and each area is called a level. The levels in the neck are numbered 1 through 7. 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.
A group of cancer cells inside of a lymph node is called a tumour deposit. If a tumour deposit is found, your pathologist will measure the deposit and the largest tumour deposit found will be described in your report.
All lymph nodes are surrounded by a thin layer of tissue called a capsule. Cancer cells that have spread to a lymph node can break through the capsule and into the tissue surrounding the lymph node. This is called extranodal extension (ENE). Extranodal extension does not change the pathologic stage but your doctors may use this information when deciding which treatment is best for you.
The pathologic stage for PTC is based on the TNM staging system, an internationally recognized system originally created by the American Joint Committee on Cancer. This system uses information about the primary tumour (T), lymph nodes (N), and distant metastatic disease (M) to determine the complete pathologic stage (pTNM). Your pathologist will examine the tissue submitted and give each part a number. In general, a higher number means a more advanced disease and a worse prognosis.
PTC is given a tumour stage between 1 and 4 based on the size of the tumour and the presence of tumour cells outside of the thyroid.
PTC is given a nodal stage of 0 or 1 based on the presence or absence of tumour cells in a lymph node and the location of the involved lymph nodes.
PTC is given a metastatic stage of 0 or 1 based on the presence of tumour cells at a distant site in the body (for example the lungs). The metastatic stage can only be determined if tissue from a distant site is sent for pathological examination. Because this tissue is rarely sent, the metastatic stage cannot be determined and is listed as MX.