Melanoma is a malignant tumor of the skin. It is estimated than more than 100,000 people will be diagnosed with the disease in the US in 2020 alone. It is the sixth most common cancer in women and the fifth in men. A metastatic melanoma is a melanoma that has spread (metastasized) to other areas of the body. The word Melanoma comes from the fact that these tumours are formed of an uncontrolled proliferation of the cells that produce the pigment of the skin: melanin. These cells are called melanocytes.
This article will cover what a metastatic melanoma is, what is stage four melanoma refers to, the symptoms of metastatic melanoma, what a metastatic melanoma can do to the brain, the treatment modalities available for a patient with metastatic melanoma, the prognosis of the disease, the life expectancy and survival rates for patients suffering from metastatic melanoma.
Background
We don’t often think of the skin as an organ, but it is – in fact- the body’s largest organ. The skin consists of two layers, with a third separate layer beneath. The most superficial layer of the skin is called the epidermis (Epi means over), and it is the body’s first line of defence against the outside environment. The second layer of the skin beneath the epidermis is named the dermis. The dermis consists of connective tissue, and contains what we call skin appendages, which include hair follicles, sweat glands, and sebaceous glands. The dermis also has blood vessels and lymphatic vessels. The layer underneath the skin is called the hypodermis, also known as the subcutis or the subcutaneous tissue. The skin has many functions. These include protecting the body from bacteria and the elements, thus being considered part of the body’s immune system, regulating the temperature of the body through perspiration, allowing the sensation of touch and the ability to feel heat and cold, synthesis of vitamin D, and covering the internal bodily structures such as muscles, tendons, blood vessels and other organs. Some medications such as the nicotine patch depends on the skin’s ability to absorb in order to deliver the drug. The skin has a surface area of about 20 square feet.
The epidermis contains the cells that are responsible for the pigmentation of the skin, which are also the cells implicated in Metastatic Melanoma – the melanocytes. Most melanocytes in the body are present in the lowermost layer of the epidermis which we call stratum basale, but they are also present in other pigmented areas of the body, such as a part of the eye called the uvea, the inner ear, the skin of the vagina, the heart, bone, and the coverings of the brain. The function of melanin is to protect the body from the sun’s harmful ultraviolet rays. Excessive destruction of melanocytes causes vitiligo, while uncontrolled proliferation of the cells causes malignant melanoma.
What is metastatic melanoma?
In general, cancers are divided into two types: benign and malignant. Both are caused by uncontrolled proliferation and division of cells, but the difference is that benign tumours always stay in one location, while malignant tumours have the ability to spread to other sites, which is called metastasis. If a malignant tumour is diagnosed early, it can be removed before metastasizing.
To understand what the term stage four metastatic melanoma refers to, we need to take a look at how physicians classify malignant tumours. According to the TNM system, tumours are organized into various stages. The criteria for classifying a tumor as being of a certain stage include the tumour size, the spread of that tumour into the nearby lymph nodes, and the spread of the tumour to distant sites. Any tumor which is found to have metastasized to other body parts is automatically labelled a stage four tumour, the least favourable stage and the most difficult one to treat.
Pathophysiology of Melanoma
There are several factors that increase the chance of developing a malignant melanoma, chief among them is exposure to ultraviolet radiation. These harmful Rays cause damage to the patient’s DNA. Sunburns are also a major risk factor. Not only is direct exposure to sunlight risky, but also tanning beds can increase your chances of the developing skin cancer. With regards to racial differences, Caucasians are more at risk when it comes to sunlight-induced melanoma, since having fair skin means less melanin, which translates to less protection from ultraviolet rays. Indeed, melanoma is twenty times more prevalent in white people than in African Americans . Unprotected sun exposure during childhood is a greater risk factor than sun exposure as an adult.
Genetic factors also play a significant role, which is why malignant melanoma tends to run in families. Having a close relative diagnosed with the disease increases your chances of developin it. About 10% of melanoma patients have a family history of the disease.
The presence of some types of moles or nevi is also a risk factor for the development of this disease. Also a patient who had a previous melanoma in the past has a higher risk of developing another one later.
Prevention of malignant melanoma
The most important measure to take in order to decrease the risk of developing melanoma is to avoid sunlight as much as possible. This can be done by avoiding peak sunlight hours and using sunscreen with a suitable SPF (Sun Protection Factor). Tanning beds are to be avoided as well.
Since patients with a family history of melanoma and those who have previously had the disease are at a higher risk of developing it, these demographics should undergo regular checkups.
Metastatic Melanoma symptoms
The symptoms of metastatic melanoma woman can be divided into two groups: Symptoms caused by the melanoma at the site where it originated, and symptoms caused by its spread to other parts of the body (metastasis).
The appearance of a new lump on the skin or the change in the appearance of an existing mole or nevus is one manifestation of malignant Melanoma. The lesion may appear asymmetrical or irregular or elevated above the skin surface. It may feel firm or begin to itch, bleed or ulcerate, or it may seem to grow or change in colour or shape over time.
Most cancers including malignant Melanoma often cause weight loss, fatigue, loss of appetite, and vomiting.
When it comes to symptoms of a stage four metastatic melanoma, these depend on the organ affected. It can spread to the bone and liver, but more commonly metastasizes to the brain. Metastatic Melanoma brain manifestations include headache, nausea, vomiting, memory and sleep problems, seizures, loss of balance, loss of vision, personality changes, muscle weakness or paralysis, difficulty walking, and drowsiness to name a few. Metastasis to a bone may cause bone pain or an increased susceptibility to fractures from minor injuries. Liver metastasis may cause jaundice or a tendency to bleed in late cases.
Diagnosis of malignant melanoma
The dermatologist will first ask about any family history of melanoma and will also ask about the risk factors that the patient may have such as excessive unprotected sunlight exposure. They will then examine the lesion in question with the naked eye or with an instrument called a dermatoscope to view the lesion in more detail. If it looks suspicious, they may order a tissue biopsy, where the bump is removed and examined under a microscope to check if the cells look abnormal, in order to determine what type of mass it is. The physician may ask the patient to disrobe completely in order to perform a total body skin examination, since a significant number of Melanomas are discovered accidentally.
As mentioned above, the tumor may spread to the nearby lymph nodes, so some patients may need a lymph node biopsy. Similarly, because of the tumour’s ability to spread into other organs, various radiographic studies may be ordered of the different body parts. These include a CT scan of the chest, abdomen, or pelvis, an MRI of the brain, or a PET scan (Positron Emission Tomography).
A blood sample may also be ordered. This allows the measurement of the levels of certain substances that are increased in case of a malignant tumour, thus they are called tumkr markers, including alkaline phosphatase and lactic acid dehydrogenase (LDH). The blood sample may also allow an assessment of the overall health of the patient and of the side effects of any medications being administered.
Treatment of malignant melanoma
The main line of treatment for malignant melanoma is surgery. Other treatment modalities may or may not be added according to the stage of the disease.
To make sure that all the malignant cells are removed from the skin, the surgeon has to remove the tumor plus a rim of surrounding skin as a “Safety margin”. This is called a wide local excision.
If the patient’s lymph nodes are confirmed to contain tumor cells, they must be removed as well to prevent the tumor from recurring. This is called lymph node dissection.
A patient with an advanced Melanoma may need additional lines of treatment in conjunction with surgical removal of the tumor. These may include the use of chemotherapy. Chemotherapeutic drugs are powerful agents which break down the tumor architecture. Choosing the appropriate chemotherapeutic agent is a pretty complex process but it should be noted that these drugs are so strong that they cause damage to the body’s normal cells, resulting in some undesirable side effects. The physician weighs the pros and cons of selecting a particular drug for each patient according to the case.
Another type of adjuvant therapy is what we call immunotherapy. This method aims to stimulate the body’s immune system and to make it more aggressive towards cancer cells.
A third add-on treatment line is targeted therapy, which actually attacks the mutated genetic material present in the tumor cells, crippling their ability to replicate and survive.
Yet another line of therapy is radiotherapy. This modality depends on using high doses of ionizing radiation such as X-rays to damage and destroy the DNA present in the cancer cells, leading to tumor destruction. However, not all tumours are sensitive to this treatment.
When it comes to stage 4 metastatic Melanoma, treatment is more difficult, and the goal becomes palliative therapy. Surgery may be performed to relieve some symptoms but is not expected to cure the patient completely. Immunotherapy, targeted therapy, and chemotherapy play a more important role in metastatic disease. Regarding metastatic melanoma that affects the brain, external beam irradiation is quite effective.
Prognosis of malignant melanoma
As with any disease, early diagnosis and treatment is associated with a far better prognosis that late discovery. Once the tumor metastasizes, survival rates fall sharply. Metastatic Melanoma survival rates are as follows:
- Melanoma at one site only: 98.4% survival rate.
- Melanoma that has spread to the local lymph nodes: 63.6% survival rate.
- Melanoma that has metastasized to distant body parts: 22.5% survival rate.
Survival rates refer to the ability of the patient to live for at least 5 years after the diagnosis has been made, hence they are more properly called “5-year survival rates”.
The impact of lymph node involvement on the prognosis depends on the number of nodes affected, and the size of the tumor tissue inside the nodes, whether it can be seen by the naked eye or if it needs a powerful microscope to visualize. Obviously, the smaller the tumor deposits the better.
Metastatic Melanoma life expectancy drops precipitously when metastases are involved, reaching an average of 6 to 12 months. Metastasis to the brain or liver is particularly bad, while metastasis to the lungs or skin is associated with a better prognosis.
Other factors that can influence the prognosis include the size of the tumor, the histological type of the melanoma, detected by examining the lesion under a microscope after a tissue biopsy. Also the thickness of the tumor, ulceration or bleeding at the site of the lesion, and the level of the tumor marker lactic acid dehydrogenase (LDH) in the blood.
Conditions that lower a person’s immunity, such as organ transplantation or being infected with the Human Immunodeficiency Virus (HIV) also worsen the prognosis, as does being older than 70 years.
On the other hand, factors that increase the likelihood of a good prognosis include being female, being young, and having the lesion on the limbs rather than the trunk.