by Jason Wasserman, MD PhD FRCPC, reviewed on March 5, 2020
The thyroid is a U-shaped gland located in the front of the neck. The normal thyroid gland is divided into right and left lobes that are connected in the middle by the isthmus. Some people also have another small lobe above the isthmus called the pyramidal lobe.
The thyroid gland makes thyroid hormone. Most of the cells in the thyroid gland are called follicular cells. The follicular cells connect together to form small round structures called follicles. Thyroid hormone is stored in a material called colloid which fills the centre of follicles.
Papillary thyroid carcinoma is a type of thyroid cancer. Papillary thyroid carcinoma develops from the follicular cells normally found in the thyroid gland. It is the most common thyroid cancer in adults. This cancer is named after the small finger like projections of tissue called papilla that are seen in some tumours.
In order to make the diagnosis of papillary thyroid carcinoma, 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 papillary thyroid carcinoma 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.
The first diagnosis of papillary thyroid carcinoma is usually made after a fine-needle aspiration (FNA) biopsy 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 some patients are treated with radioactive iodine to kill any remaining cancer cells.
The type of treatment you will receive depends on several features including the size of the tumour, the histologic variant, the presence of cancer cells outside of the thyroid gland, and the presence of cancer cells in a lymph node. All of these features can only be determined after your pathologist examines your tissue under the microscope.
There are many different types of papillary thyroid carcinoma and each type is called a variant. Your pathologist will determine the variant by examining the tissue under the microscope and looking at the size and shape of the cancer cells and the way they stick together as they grow.
Variants of papillary thyroid carcinoma include:
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.
This is the size of the tumour measured in centimeters (cm). Tumour size will only be described in your report after the entire tumour has been removed. 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.
Why is this important? Tumour size plays an important role in determining the pathologic tumour stage for papillary thyroid carcinoma (see Pathologic stage below).
A microcarcinoma is a tumour that measures less than 1.0 cm in size. Most microcarcinomas are of the classic or follicular variant type (see Variants). Prognosis is very good when a microcarcinoma is the only tumour found after microscopic examination of the thyroid gland.
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.
Why is this important? When more than one tumour is found, only the largest tumour is used to determine the pathologic tumour stage (pT) (see Pathologic stage below).
Some tumours are separated from the surrounding normal thyroid gland by a thin tissue barrier called a capsule. These tumours are called called encapsulated. If only part of the tumour is surrounded by a capsule, the tumour is called partially encapsulated.
A capsule is commonly seen around the follicular variant of papillary thyroid carcinoma (see Types of papillary thyroid carcinoma above). In order to make the diagnosis of papillary thyroid carcinoma, follicular variant, your pathologist must see tumour cells going past the capsule into the surrounding normal thyroid tissue. Pathologists call this tumour capsule invasion.
A tumour that has no capsule separating it from the surrounding normal thyroid gland is called non-encapsulated or infiltrative. Cancer cells in infiltrative tumours are more likely to spread to lymph nodes or distant sites such as the lungs or bones.
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:
Why is this important? Macroscopic (gross) extrathyroidal extension increases the tumour stage (see Pathologic stage below) and is associated with worse prognosis. Microscopic extrathyroidal extension does not change the tumour stage.
Blood vessels carry blood around the body. Tumour cells that enter a blood vessel are able to spread (metastasize) to distant parts of the body such as the lungs and bones.
Tumour cells seen inside of a blood vessel is called vascular invasion (angioinvasion). If vascular invasion is seen, your pathologist will count the number of vessels that contain tumour cells.
Your report will describe vascular invasion as negative if no cancer cells are seen inside of a blood vessel, positive and focal if there are less than 4 blood vessels with cancer cells, and positive an diffuse if there are 4 or more blood vessels with cancer cells.
Why is this important? Vascular invasion is important because tumour cells that enter a blood vessel are more likely to spread to other parts of the body. The movement of tumour cells from the tumour to another part of the body is called a metastasis.
Lymphatics are small thin vessels that provide a way for fluids and cells to leave a tissue. Lymphatics are found all over the body. Tumour cells that enter a lymphatic vessel are able to spread to other parts of the body, in particular lymph nodes.
Tumour cells seen inside a lymphatic vessel is called lymphatic invasion. Your pathologist will carefully examine your tissue for lymphatic invasion. If lymphatic invasion is seen, it will be called positive. If no lymphatic invasion is seen, it will be called negative.
Why is this important? Lymphatic invasion is important because tumour cells that enter a lymphatic space are more likely to spread to lymph nodes or other parts of the body. The movement of tumour cells from the tumour to another part of the body is called a metastasis.
A margin is the tissue that has to be cut by the surgeon to remove the thyroid gland from your body. A margin is considered positive when there are cancer cells at the very edge of the cut tissue. A negative margin means there were no cancer cells seen at the cut edge of the tissue.
Lymph nodes are small immune organs located throughout the body. Tumour 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 tumour cells from the thyroid to a lymph node is called a metastasis.
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.
Your pathologist will carefully examine each lymph node for tumour cells. Lymph nodes that contain tumour 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.
Why is this important? Papillary thyroid carcinoma is frequently found in lymph nodes in the neck although this is not necessarily associated with worse prognosis especially in younger patients.
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 capsule. Extranodal extension (ENE) means that cancer cells have broken through the capsule and into the tissue that surrounds the lymph node.
The pathologic stage for papillary thyroid carcinoma 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 more advanced disease and worse prognosis.
The pathologic stage will only be included in your report after the entire tumour has been removed. It is not included in your report after a biopsy or fine needle aspiration.
Tumour stage (pT) for papillary thyroid carcinoma
Papillary thyroid carcinoma 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 (see Extrathyroidal extension above).
Nodal stage (pN) for papillary thyroid carcinoma
Papillary thyroid carcinoma 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.
Metastatic stage (pM) for papillary thyroid carcinoma
Papillary thyroid carcinoma 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.