by Allison Osmond, MD FRCPC, updated on September 4, 2019
Skin is made up of three layers: epidermis, dermis, and subcutaneous fat. The surface and the part you can see when you look at your skin is called the epidermis. The cells that make up the epidermis include: squamous cells, basal cells, melanocytes, Merkel cells, and cells of the immune system (see picture below). The squamous cells in the epidermis produce a material called keratin which makes the skin waterproof and strong and protects us from toxins and injuries.
The dermis is directly below the epidermis. The dermis is separated from the epidermis by a thin layer of tissue called the basement membrane. The dermis contains blood vessels and nerves. Below the dermis is a layer of fat called subcutaneous adipose tissue.
Merkel cells are a special type of skin cell that has multiple jobs. For example, Merkel cells help tell your brain when something is touching your skin. They also send signals to other skin cells including keratinocytes and the cells that form the sweat glands in your skin. Because Merkel cells are involved in sending signals to other cells, they are part of a family of cells called a neuroendocrine cells.
Merkel cell carcinoma is a type of skin cancer. It develops from the Merkel cells in the epidermis. In Merkel cell carcinoma, the abnormal Merkel cells break out of the epidermis and enter the dermis below. The movement of cancer cells from the epidermis into the dermis is called invasion.
Normal Merkel cells are long and skinny and they are not easily seen through the microscope. However, in Merkel cell carcinoma, the abnormal Merkel cells increase both in size and in number which allows you pathologist to easily see them through the microscope.
Another name for Merkel cell carcinoma is primary neuroendocrine carcinoma of the skin.
Merkel cell carcinoma usually occurs in older individuals who have a history of prolonged exposure to sun and sun burns. However, Merkel cell carcinoma can also be occur in younger patients and this is commonly seen in people who have weakened immune systems for a variety of reasons. In younger patients, a virus called Polyoma virus is believed to play a role in the development Merkel cell carcinoma.
This is the size of the tumour measured in centimetres. Your report may only describe the greatest dimension. For example, if the tumour measures 5.0 cm by 3.2 cm by 1.1 cm, the report may describe the tumour size as 5.0 cm in greatest dimension.
The tumour size is only described after the entire tumour has been removed. Tumour size is not reported after a biopsy.
The tumour size is used to determine the tumour stage (see Pathologic stage below). Tumours that are larger than 2 centimetres are more likely to re-grow after treatment or to spread to other areas of the body.
All Merkel cell carcinomas start in the epidermis on the outer surface of the skin. Depth of invasion describes how far the cancer cells have traveled from the epidermis into the tissue below. The movement of cancer cells from the epidermis into the tissue below is called invasion.
Some reports use the term tumour thickness to describe the depth of invasion.
The depth of invasion is measured from the surface of the skin to the deepest point of invasion. The depth of invasion is measured in millimetres (mm).
Tumours that invade deep into the dermis or subcutaneous adipose tissue are more likely to spread to other parts of the body. The depth of invasion is also used to determine the tumour stage (see Pathologic stage below).
Large tumours can grow beyond the skin into bone, muscle, or cartilage. Pathologists will use tumour extension to describe tumours that have grown into any of these types of tissue.
Tumour extension into bone, muscle, or cartilage is associated with an increased risk that the tumour will spread to other parts of the body or will re-grow in the same location after treatment. Tumour extension is also used to determine the tumour stage (see Pathologic stage below).
Pattern of growth is used to describe how the cancer cells look when examined under the microscope.
There are two main patterns of growth:
Tumours that grow in a nodular pattern tend to be associated with a better prognosis compared to tumours that grow in an infiltrative pattern.
Merkel cell carcinoma can sometimes be found with other tumours of the skin such as squamous cell carcinoma and basal cell carcinoma. If your pathologist sees a second cancer, it will be described in your report.
Lymphocytes are specialized cells that are part of the body’s immune system. Lymphocytes respond to infections, injury, or cancer. Lymphocytes are frequently found in the tissue around Merkel cell carcinoma and their presence is considered a sign that the body is attempting to prevent the spread of the disease.
There are two ways to describe the lymphocytes around the tumour:
Non-brisk tumour infiltrating lymphocytes is associated with worse prognosis.
A margin is the normal tissue that surrounds a tumour and is removed with the tumour at the time of surgery. In most cases, surgeons will try to remove 1 cm of normal tissue around the entire tumour.
The normal skin surrounding the tumour is called the peripheral margin while be tissue below the tumor is called the deep margin. Both margins are closely examined under the microscope to see if there are any cancer cells in the normal looking tissue.
If no cancer cells are seen at the cut edge of the tissue the margin is called negative.
If cancer cells are seen at the very edge of the cut tissue, the margin is called positive. A positive margin is important because it is associated with a greater risk that the tumour will come back in the same location (local recurrence) after treatment.
When a cell divides in order to create a new cell the process is called mitosis. Pathologists frequently count the number of mitoses in a tumour and this count is called the mitotic rate.
Most pathology reports describe the mitotic rate as the number of mitotic cells per millimetre square.
Tumours with more mitotic figures are associated with worse prognosis.
Blood moves around the body through long thin tubes called blood vessels. Another type of fluid called lymph which contains waste and immune cells moves around the body through lymphatic channels.
Cancer cells can use blood vessels and lymphatics to travel away from the tumour to other parts of the body. The movement of cancer cells from the tumour to another part of the body is called metastasis.
Before cancer cells can metastasize, they need to enter a blood vessel or lymphatic. This is called lymphovascular invasion.
Lymphovascular invasion increases the risk that cancer cells will be found in a lymph node or a distant part of the body such as the lungs.
Cancer cells that leave the main tumour and travel to another part of the body are called a metastasis. Cancer cells often travel to a lymph node which is called a lymph node metastasis (see Lymph nodes below). Merkel cell carcinoma cancer cells that are found outside of the main tumour but not in a lymph node are called an in-transit metastasis.
The finding of an in-transit metastasis is important because it increases the nodal stage (see Pathologic stage below) and is associated with worse prognosis.
Lymph nodes are small immune organs located throughout the body. Cancer cells can travel from the tumour to a lymph node through lymphatic channels located in and around the tumour (see Lymphovascular invasion above). The movement of cancer cells from the tumour to a lymph node is called a metastasis.
If your tumour was located on your face or head, lymph nodes from the neck are sometimes removed at the same time as the main tumour 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 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.
A sentinel lymph node is the closest lymph node to the tumour. When Merkel cell carcinoma travels to a lymph node, it usually goes to the sentinel node first. All other lymph nodes in the area of the tumour are simply referred to as regional lymph nodes. Your pathology report will specify which lymph nodes are involved.
Most reports include the total number of lymph nodes examined and the number that contain cancer cells. Lymph nodes that contain cancer cells are often called positive while those that do not contain any cancer cells are called negative.
Your pathologist may use special tests such as immunohistochemistry in order to see if there are any cancer cells in the examined lymph nodes. For example, Merkel cells make proteins called cytokeratins and immunohistochemistry is can help pathologists see cells that make cytokeratins.
Lymph nodes are used to determine the nodal stage (see Pathologic stage below). Your doctors will use the nodal stage together with the tumour stage to determine the best treatment options for you.
The pathologic stage for Merkel cell 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 can only be determined after the entire tumour has been removed.
Tumour stage (pT) for Merkel cell carcinoma:
Merkel cell carcinoma is given a tumour stage between 1 and 4 based on the size of the tumour and whether or not the tumour grows into other tissues like bone, muscle, fascia or cartilage.
Nodal stage (pN) for Merkel cell carcinoma:
Merkel cell carcinoma is given a nodal stage of 0 to 3 based on the presence of cancer cells in a lymph node and in-transit metastases.
If no lymph nodes are sent for pathological examination, the nodal stage cannot be determined and the nodal stage is listed as pNX.
Metastatic stage (pM) for Merkel cell carcinoma:
Merkel cell carcinoma is given a metastatic stage of M0 or M1 based on the presence of cancer cells outside of the main tumour. Cancer cells that have traveled to a distant body site are also considered metastatic disease but are given a lower metastatic stage than cancer cells that have traveled to 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 present, the metastatic stage cannot be determined and is listed as pMX.