Invasive melanoma of the skin

By Jason Wasserman MD PhD FRCPC
April 19, 2023

What is invasive melanoma?

Invasive melanoma is a common type of skin cancer made up of cells called melanocytes. This type of skin cancer is more common in people with light skin tones who have a history of long-term sun exposure.

Where does invasive melanoma start?

Invasive melanoma starts from specialized cells called melanocytes normally found in a part of the skin called the epidermis. As the tumour grows, the abnormal melanocytes spread into a layer of skin called the dermis. Large tumours can eventually spread into even deeper layers of tissue such as the subcutaneous adipose tissue (fat below the skin) and muscle. The spread of abnormal melanocytes from the epidermis into the tissue below is called invasion.

What causes invasive melanoma?

Most invasive melanomas in the skin are caused by long-term exposure to UV radiation, typically from the sun although other sources of UV light such as tanning beds can have a similar effect. UV radiation causes genetic changes in the melanocytes which leads to the development of cancer. Melanomas not caused by long-term sun exposure, such as those arising from a mole, are much less common.

What does invasive melanoma look like?

Most invasive melanomas are pigmented which means they appear darker than the surrounding skin. Multiple colours including brown, black, red, and blue may be seen. The border of the tumour is often irregular which means it can be difficult to tell where the tumour ends and the normal skin begins. Some types of invasive melanoma are flat and slow growing while other types appear are raised and fast-growing tumours. Over time the tumour can start to bleed.

What are the types of invasive melanoma?

Invasive melanoma of the skin is divided into types based on the way the tumour cells grow and spread through the skin. The most common types of invasive melanoma are superficial spreading melanoma, nodular melanoma, and lentigo maligna melanoma.

Superficial spreading melanoma

In superficial spreading melanoma, the tumour cells spread along the epidermis and in the most superficial parts of the dermis (the layer of skin just below the epidermis). The surrounding skin often shows changes associated with a moderate amount of sun damage including solar elastosis. This type of invasive melanoma often starts from a non-invasive type of skin cancer called melanoma in situ.

Nodular melanoma

In nodular melanoma, most of the tumour cells are found in the dermis (the layer of skin just below the epidermis). The tumour cells are often found in large groups that may be described as sheets or nests. Tumour cells may also be found in the epidermis overlying the large groups of tumour cells. Compared to the other types of melanoma, nodular melanoma grows more quickly and is more likely to spread to other parts of the body.

Lentigo maligna melanoma

In lentigo maligna melanoma the tumour cells are found primarily along the border between the epidermis and the dermis in an area called the dermal-epidermal junction. Tumour cells will also be found in the superficial dermis (just below the epidermis). In contrast to the superficial spreading type of melanoma, the skin surrounding lentigo maligna melanoma will show changes associated with severe sun exposure including extensive solar elastosis. Lentigo maligna melanoma often starts from a non-invasive type of skin cancer called lentigo maligna (also known as melanoma in situ).

What does tumour thickness mean and why is it important for invasive melanoma?

All invasive melanomas start in the epidermis, a thin layer of tissue on the surface of the skin. As the tumour grows, the cells spread into the layers of tissue below the epidermis including the dermis and subcutaneous adipose tissue. The spread of tumour cells in this way is called invasion. Tumour thickness (also known as Breslow’s thickness) is the distance from the epidermis to the deepest point of invasion. The tumour thickness is important because it is used to determine the pathologic tumour stage (pT) and because thicker tumours are more likely to spread to other parts of the body such as lymph nodes and the lungs.

What does ulceration mean and why is it important for invasive melanoma?

Ulceration is a type of tissue damage that results in the loss of cells on the surface of a tissue. For skin tumours such as invasive melanoma, ulceration refers to the loss of cells in the epidermis over the tumour. Invasive melanomas that cause ulceration are associated with a worse prognosis. Ulceration is also used to determine the pathologic tumour stage (pT).

What does the mitotic rate mean and why is it important for invasive melanoma?

A mitotic figure (or mitosis) is a cell that is dividing to create two new cells. For tumours such as invasive melanoma, pathologists count the number of mitotic figures in a specified area of tissue (for example 1 mm2) and the count is called the mitotic rate. For invasive melanoma, the mitotic rate is important because tumours with a higher rate grow more quickly and are more likely to spread to other parts of the body.

What is a microsatellite and why is it important for invasive melanoma?

For invasive melanoma, a microsatellite is a group of tumour cells that have spread from the primary tumour (the place where the tumour started) to a nearby area of skin. Another name for a microsatellite is cutaneous metastasis. Microsatellites are important because they increase the pathologic nodal stage (pT).

What are tumour-infiltrating lymphocytes and why are they important for invasive melanoma?

The term tumour infiltrating lymphocytes (TILs) is used to describe specialized immune cells called lymphocytes surrounding or spreading into the tumour. Current evidence shows that TILs can kill and remove tumour cells. For this reason, the more TILs seen, the better.

Most pathologists will categorize the number of tumour-infiltrating lymphocytes as follows:

• No tumour-infiltrating lymphocytes were identified.
• Non-brisk (very few tumour infiltrating lymphocytes)
• Brisk (lots of tumour infiltrating lymphocytes)

What does lymphovascular invasion mean and why is this important for invasive melanoma?

Lymphovascular invasion means that cancer cells were seen inside a blood vessel or lymphatic vessel. Blood vessels are long thin tubes that carry blood around the body. Lymphatic vessels are similar to small blood vessels except that they carry a fluid called lymph instead of blood. The lymphatic vessels connect with small immune organs called lymph nodes that are found throughout the body. Lymphovascular invasion is important because cancer cells can use blood vessels or lymphatic vessels to spread to other parts of the body such as lymph nodes or the lungs.

What does neurotropism mean and why is it important?

Neurotropism (also known as perineural invasion) is a term pathologists use to describe cancer cells attached to or inside a nerve. Nerves are like long wires made up of groups of cells called neurons. Nerves are found all over the body and they are responsible for sending information (such as temperature, pressure, and pain) between your body and your brain. Neurotropism is important because the cancer cells can use the nerve to spread into surrounding organs and tissues. This increases the risk that the tumour will regrow after surgery.

What does tumour regression mean and why is it important?

Tumour regression is the gradual disappearance of tumour cells from an area where tumour cells were previously found. The tumour cells are often replaced by immune cells or a type of scar tissue called fibrosis. Tumour regression is believed to be caused by immune cells that attack and kill the tumour cells. Invasive melanoma can show partial or complete tumour regression.

Were lymph nodes examined and did any contain cancer cells?

Lymph nodes are small immune organs found throughout the body. Cancer cells can spread from a tumour to lymph nodes through small vessels called lymphatics. 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.

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.

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. Most reports will include the total number of lymph nodes examined, where in the body the lymph nodes were found, and the number (if any) that contain cancer cells. If cancer cells were seen in a lymph node, the size of the largest group of cancer cells (often described as “focus” or “deposit”) will also be included.

The examination of lymph nodes is important for two reasons. First, this information is used to determine 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 chemotherapy, radiation therapy, or immunotherapy is required.

What does it mean if a lymph node is described as positive?

Pathologists often use the term “positive” to describe a lymph node that contains cancer cells. For example, a lymph node that contains cancer cells may be called “positive for malignancy” or “positive for metastatic melanoma”.

What does it mean if a lymph node is described as negative?

Pathologists often use the term “negative” to describe a lymph node that does not contain any cancer cells. For example, a lymph node that does not contain cancer cells may be called “negative for malignancy” or “negative for metastatic melanoma”.

What is a sentinel lymph node?

A sentinel lymph node is the first lymph node in the chain of lymph nodes that drains fluid from the skin involved by the tumour. The location of the sentinel lymph node depends on the location of the tumour.

What is a non-sentinel lymph node?

A non-sentinel lymph node is located after the sentinel lymph node. Cancer cells usually spread to these lymph nodes after passing through the sentinel lymph node.

What does extranodal extension mean?

All lymph nodes are surrounded by a thin layer of tissue called a capsule. Extranodal extension means that cancer cells within the lymph node have broken through the capsule and have spread into the tissue outside of the lymph node. Extranodal extension is important because it increases the risk that the tumour will regrow in the same location after surgery. For some types of cancer, extranodal extension is also a reason to consider additional treatment such as chemotherapy or radiation therapy.

What is a margin?

In pathology, a margin is the edge of a tissue that is cut when removing a tumour from the body. The margins described in a pathology report are very important because they tell you if the entire tumour was removed or if some of the tumour was left behind. The margin status will determine what (if any) additional treatment you may require.

Pathologists carefully examine the margins to look for tumour cells at the cut edge of the tissue. If tumour cells are seen at the cut edge of the tissue, the margin will be described as positive. If no tumour cells are seen at the cut edge of the tissue, a margin will be described as negative. Even if all of the margins are negative, some pathology reports will also provide a measurement of the closest tumour cells to the cut edge of the tissue.

A positive (or very close) margin is important because it means that tumour cells may have been left behind in your body when the tumour was surgically removed. For this reason, patients who have a positive margin may be offered another surgery to remove the rest of the tumour or radiation therapy to the area of the body with the positive margin.