Skin -

Melanoma

This article was last reviewed and updated on September 4, 2019
by Allison Osmond, MD FRCPC
Artwork by Zuzanna Gorski, MD

Quick facts:

  • Melanoma is a type of cancer that develops from special cells called melanocytes.

  • Melanoma can start any where in the body where there are normally melanocytes although the most common location is the skin.

  • In the skin, melanoma is associated with excessive sun exposure (sun burns).

Normal skin

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. 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.

Melanocytes

Melanocytes are small cells that produce melanin, a dark pigment that helps protect our skin from the sun’s ultraviolet rays. 

The amount of melanin normally found in our skin determines our skin colour. People with very light skin produce very little melanin while people with very dark skin produce a lot of melanin. 

What is melanoma?

Melanoma is a type of skin cancer that develops from special cells called melanocytes. Melanoma is a common type of skin cancer although it can rarely start in other sites such as the inside of the eye, mouth, nasal cavity, or esophagus. In the skin, melanoma is associated with excessive sun exposure especially multiple severe sun burns.

 

When the cancer cells are only seen in the epidermis, the disease is called melanoma in situ (lentigo maligna). Once the abnormal melanocytes break out of the epidermis and enter the dermis below, the disease is called invasive melanoma. The movement of cancer cells from the epidermis into the dermis is called invasion.

 

Melanoma is usually diagnosed after a small sample of tissue is removed in a procedure called a biopsy. The tumour is later removed surgically and is sent to pathology for examination.

Tumour size

After the tumour has been removed fully, your pathologist will measure it in three dimensions although only the largest dimension is typically included in your report. 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.

Histologic type

There are different types of melanoma and each is called a histologic type. Your pathologist will decide the histologic type by looking at the size and shape of the cancer cells and the way the cancer cells stick together as the tumour grows. These features can only be seen by examining the tumour under the microscope. 

Histologic types of melanoma include:

  • Superficial spreading - When examined under the microscope, most of the tumour is growing below the epidermis. Less tumour is seen growing downward into the dermis.

  • Nodular - This type of melanoma is the opposite of the superficial spreading type. When examined under the microscope, most of the tumour is growing downward into the epidermis. Less tumour is seen growing under the epidermis.

If the cancer cells are only seen in the epidermis, the tumour is considered to be non-invasive and the histological type is called melanoma in situ.

Why is this important? The histological type is important because some types such as superficial spreading are less likely to spread (metastasize) to other parts of the body.

Maximum tumor thickness (Breslow thickness)
All melanomas start in the epidermis on the surface of the skin. The tumour thickness or Breslow thickness 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.

 

The tumour thickness is measured from the surface of the skin to the deepest point of invasion. The maximum tumour thickness is measured in millimeters.

 

Why is this important? The tumour thickness or Breslow thickness is the most important prognostic factor and it is used to determine the tumor stage (see Pathological stage below). Thicker tumours are more likely to spread to lymph nodes or other parts of the body. The spread of cancer cells outside of the tumour is called metastasis.

Ulceration
An ulcer is an area of skin where the epidermis has been damaged. In an ulcer the epidermis has been lost and the dermis below is exposed.

 

Why is this important? An ulcer over a melanoma is associated with worse prognosis and is also used to determine the tumour stage (see Pathological stage below).

Macroscopic satellite nodules

A macroscopic satellite nodule is a large group of cancer cells that are separated from the main tumour. These nodules are big enough to be seen without a microscope. If your tumour has macroscopic satellite nodules, this information will be is found under the gross description section of your pathology report.

Microsatellite tumour nodules

Microscopic satellite nodules are groups of cancer cells that can only be seen with a microscope.  Like macroscopic satellite nodules, microscopic nodules are separate from the tumour.

 

Why is this important? Tumours with microscopic satellite nodules are more likely to be spread to a lymph node or distant body site. For that reason, microsatellite tumour nodules are associated with worse prognosis.

Tumour infiltrating lymphocytes

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:

 

  • Brisk - This means that lots of lymphocytes were seen in and around the tumour. 

  • Non-brisk - This means that very few lymphocytes were seen around the tumour.

Why is this important? Tumours with non-brisk tumour infiltrating lymphocytes are more likely to spread to a lymph node or a distant part of the body such as the lungs.

Margins

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 for cancer cells in the normal looking tissue.

 

If cancer cells are seen at the very edge of the cut tissue the margin is considered positive. If no cancer cells are seen at the cut edge of the tissue the margin is considered negative.

Why is this important? A positive margin is associated with an increased risk that the tumour will come back in the same location after surgery (local recurrence).

Mitotic rate

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 millimeter square. The mitotic rate is only described for invasive melanoma.

 

Why is this important? Tumours with more mitotic figures are associated with worse prognosis

Lymphovascular invasion

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.


Why is this important? 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.

Neurotropism (perineural invasion)

Cancer cells wrapped around a nerve in the skin is called neurotropism or perineural invasion.

 

Neurotropism allows the cancer cells to travel out of the tumour and into the surrounding normal tissue.

 

Why is this important? Neurotropism is associated with a higher risk that the tumour will come back either in the same site (local recurrence) or in a lymph node after treatment.

Tumour regression

Tumour regression is the partial or complete disappearance of the main tumour and is usually assumed to be a result of the body's immune system attacking the cancer cells. The presence of tumour regression however does not mean that the cancer is gone and cancer cells may still travel to other parts of the body.

 

Tumour regression can only be identified after microscopic examination of the tissue and will be described as partial if some cancer cells are still seen or complete if there are no cancer cells left in the area where the tumour was previously located.

Lymph nodes

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 the cancer cells in melanoma travel to a lymph node, they 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.

 

Tumour deposit

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.

Types of tumour deposits:

  • Isolated tumour cells - Individual cells not forming groups.

  • Micro-deposit - Small groups of tumour cells.

  • Macro-deposit - Large groups of tumour cells that may fill up the entire lymph node.

Why is this important? Macro-deposits are associated with worse prognosis. The size of the largest tumour deposit is also used to determine the nodal stage (see Pathologic stage below).

Extranodal extension (ENE)

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.

 

Why is this important? Extranodal extension is also associated with a higher risk of new tumours developing in the neck and is often used by your doctors to guide your treatment. Extranodal extension is also used to determine the nodal stage (see Pathologic stage below).

Pathologic stage

​The pathologic stage for melanoma 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.

 

Pathologic stage is not reported on a biopsy specimen. It is only reported when the entire tumour has been removed in an excision or resection specimen.


Tumour stage (pT) for melanoma 

Melanoma is assigned a tumour stage between 1 and 4 based on the maximum tumour thickness (Breslow thickness) and the presence or absence of ulceration. In general tumours with a greater thickness or ulceration receive a higher tumour stage.

Nodal stage (pN) for melanoma

Melanoma is given a nodal stage of 0 to 3 based on the presence of cancer cells in a lymph node, the number of lymph nodes involved, and the presence of tumour satellites.

 

If no lymph nodes are involved the nodal stage is N0. If no lymph nodes are sent for pathological examination, the nodal stage cannot be determined and the nodal stage is listed as NX.

Metastatic stage (pM) for melanoma

Melanoma is given a metastatic stage between 0 and 1 based on the presence of cancer 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 submitted for pathological examination. Because this tissue is rarely present, the metastatic stage cannot be determined and is listed as MX.

Molecular tests

Each cell in your body contains a set of instructions that tell the cell how to behave. These instructions are written in a language called DNA and the instructions are stored on 46 chromosomes in each cell. Because the instructions are very long, they are broken up into sections called genes and each gene tells the cell how to produce piece of the machine called a protein.

 

If the DNA becomes damaged or if it cannot be read accurately, the cell will be unable to produce the proteins it requires to function normally. An area of damaged DNA is called a mutation and mutations are one of the most common causes of cancer in humans.

Why is this important? It is common for a melanoma to contain mutations. These mutations involve genes that allow melanoma cancer cells to grow faster than normal cells.

 

Your tumor will be automatically tested for mutations if any of the following conditions are met:

 

  • The tumour is very thick (Breslow thickness).

  • The surface of the tumour is ulcerated.

  • Cancer cells are found in a lymph node.

  • Cancer cells have spread to a distant organ.

 

In many hospitals, pathologists perform molecular tests to look for mutations in the following genes:

 

  • BRAF

  • CKIT

  • GNAQ

  • NRAS

 

The results of the molecular tests may be included with your main pathology report or they may be included in a separate molecular pathology report. Your report will say which genes were tested and if a mutation was found in any of the genes. If a mutation was found, the specific type of mutation may be described. 

 

Why is this important? Your doctors will use these results to select medications that are specifically designed for the genetic changes identified in your tumour.

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