What is Malignant Melanoma Metastatic to the Central Nervous System?
Malignant melanoma is a severe type of skin cancer. It starts from cells called melanocytes, which originally come from other cells named neural crest cells. How long a person lives after being diagnosed (usually measured in terms of 5 years) depends on how advanced the disease is when it’s discovered. People with advanced melanoma are more likely to have their cancer spread to other parts of the body. This part of the discussion will focus on when melanoma spreads to the central nervous system, which includes the brain and spinal cord.
What Causes Malignant Melanoma Metastatic to the Central Nervous System?
Melanoma, a type of skin cancer, can be caused by a few different things:
* UV radiation or sunlight exposure
* Indoor tanning
* A special type of treatment for skin conditions called PUVA therapy
* Having light skin or poor ability to tan
* Certain genetic conditions, such as FAMM syndrome and atypical mole syndrome
* A personal or family history of melanoma
* Having a weakened immune system due to conditions like HIV, lymphoma, or a history of organ transplant
* Certain medications, like TNF inhibitors and BRAF inhibitors
There are also certain risk factors that can increase the chances of melanoma spreading to the brain (also known as CNS metastasis):
* Being a man over the age of 60
* Having a deep, invasive, or ulcerated melanoma spot
* A type of growth called acral, lentiginous, or nodular histology
* Having more than three lymph nodes involved
* Having melanoma spread to other parts of the body at diagnosis
* Having certain genetic changes, like BRAF and NRAS mutations
* Activation of a cellular pathway known as PI3K/AKT
* Having higher levels of a blood marker called LDH.
Risk Factors and Frequency for Malignant Melanoma Metastatic to the Central Nervous System
Melanoma is a type of skin cancer that is becoming more common globally, and it’s now the fifth most common cancer among both men and women in the United States. Even with the rise in cases, fewer people are dying from melanoma, likely due to better screening programs. Melanoma is not very common in children and teenagers, but its likelihood increases as people age. It’s more frequently seen in people with white skin compared to those with black or Asian skin.
Melanoma can sometimes lead to a severe complication known as Brain metastases (BM), particularly in advanced stages of the disease. In fact, melanoma is responsible for roughly 10 percent of all BM cases, making it the third most common cause after lung and breast cancer. According to a large study, about 15 percent of patients with Stage III melanoma develop BM, mostly within the first three years following surgery. The majority of these BM are found in the upper part of the brain, with around 15 percent located in the lower parts.
Signs and Symptoms of Malignant Melanoma Metastatic to the Central Nervous System
Brain metastases (BM) in patients with melanoma can cause a variety of health issues and its symptoms can vary greatly. It’s often found in individuals who have been diagnosed with malignant melanoma and are experiencing unusual neurological symptoms or changes in behavior. Most of the time, these symptoms are the result of the growth of the metastases and swelling around the lesions in the brain. Many patients don’t initially show symptoms.
- Headaches are the most common symptom, affecting 40% to 50% of patients.
- Nausea, vomiting, abnormal neurologic exam, and changes in body position may indicate BM.
- 20-40% of patients may have focal neurological symptoms (symptoms that affect only one area of the body).
- Other symptoms can include cognitive dysfunction, stroke, and seizures.
- Brain metastases in melanoma can also have a high tendency for spontaneous bleeding.
Testing for Malignant Melanoma Metastatic to the Central Nervous System
In order to confirm a diagnosis of brain metastases (which are cancerous tumors that have spread to the brain from another part of the body), we need to tell them apart from tumors that started in the brain. One tool doctors use for this are imaging tests that allow us to see inside the brain. Occasionally, we might have to take a small sample of the brain tissue (a biopsy) for testing, but this is not common.
A machine called a magnetic resonance imaging scanner (MRI) is most often used for this purpose. It’s especially good when used with a special dye (known as contrast) that helps us see the images more clearly. Non-contrast MRIs and computerized tomography scans (CT scans), another type of imaging test, are not as sensitive and might not pick up on smaller or less obvious changes.
There are certain things that can make us suspect that a person’s symptoms are due to brain metastases rather than a primary brain tumor. First, brain metastases often appear as multiple lesions, or abnormal areas, on the scans. They also have a characteristic location where they tend to show up, which is at the junction of gray and white matter in the brain. Gray and white matter are different types of brain tissue. Brain metastases are often associated with a large amount of swelling (known as vasogenic edema) and have clearly defined edges, or margins.
Treatment Options for Malignant Melanoma Metastatic to the Central Nervous System
Treating melanoma that has spread to the brain requires a team of different medical specialists, which is a strategy strongly recommended by the National Comprehensive Cancer Network. Traditional treatment for melanoma brain metastasis often includes whole-brain radiation therapy and targeted radiosurgery for a smaller number of lesions.
It was once thought that the central nervous system (brain and spinal cord) was a “sanctuary” where systemic (whole-body) treatments couldn’t reach. But, recent research suggests that systemic treatment methods can be effective in treating brain metastasis.
Advancements in brain surgery, targeted radiation options, and the use of systemic treatments like immunotherapy and specific drugs known as BRAF and MEK inhibitors, have significantly improved patient outcomes.
Some important factors to consider when treating newly diagnosed brain metastasis in melanoma patients include:
1. The final treatment plan is individualized for each patient and takes into account the number, size, and location of brain lesions; symptoms; the extent of disease spread outside the brain; the mutation status of the BRAF gene in the tumor; the patient’s overall health status; and previous treatments received.
2. In patients with no previous treatment and small (<1cm), minimally symptomatic or asymptomatic brain lesions, surgery or targeted radiation can often be postponed in favour of systemic treatment, but careful monitoring for disease progression in the brain is needed. The choice of systemic treatment depends on whether the melanoma has a specific mutation in the BRAF gene. For tumors with this mutation, targeted therapy with BRAF and MEK inhibitors, as well as immunotherapy, is effective. For tumors without this mutation, combination immunotherapy is a reasonable option. 3. In contrast, when brain lesions are larger and causing symptoms, the priority is to control the disease locally, which often means utilizing surgery or targeted radiation before systemic treatment. Supportive care, such as using steroids to reduce brain swelling, may also be necessary. 4. For patients who are not suitable for surgery, radiation therapy alone (either targeted or whole-brain) might be a viable option. Periodic brain scanning using MRI or contrast-enhanced CT is essential to monitor treatment progress. The frequency of these scans can range from every 8 to 12 weeks, depending on whether or not the patient has had surgery or radiation therapy.
What else can Malignant Melanoma Metastatic to the Central Nervous System be?
In individuals who had cancer in the past, about 10% of lumps found in the brain may not be linked to their previous cancer. When doctors find these kinds of lumps, there are a few conditions they might consider as possible causes:
- An abscess, or a pocket of infection
- Acute demyelinating disorders, which are conditions that damage the protective covering of nerve cells
- Progressive multifocal leukoencephalopathy, a rare and usually fatal viral disease characterized by progressive damage to the white matter of the brain
- Radiation necrosis, which is tissue damage caused by radiation therapy
- Granuloma, which is a kind of inflammation
- Tumors in the brain, such as gliomas and astrocytomas
- Stroke
- Multiple sclerosis, a long-lasting disease that can affect your brain, spinal cord, and the optic nerves in your eyes
- Nonbacterial thrombotic endocarditis, which involves small clots forming on heart valves
Surgical Treatment of Malignant Melanoma Metastatic to the Central Nervous System
Over the years, advancements in neurosurgery have led to a better handling of brain metastases (BM). Brain metastasis is when cancer cells spread from their original site to the brain. Surgery is usually the best option for patients who have a large lesion (usually bigger than 3cm), a single or very few brain lesions, superficial lesions located in areas where surgery won’t cause significant loss of function, or metastatic lesions in the back part of the brain that cause complications such as brain herniation. Brain herniation is a serious condition where parts of the brain get pushed past structures within the skull. Patients who perform well on the Karnofsky performance status – a standard way of measuring a patient’s ability to perform daily activities – with a score of 90 to 100, can also be ideal candidates for surgery.
After surgery, patients usually undergo Stereotactic Radiosurgery (SRS) to the part of the brain where the tumor was removed in order to reduce the chances of the tumor coming back. Even though no studies with strict controls and randomization have been conducted, research has shown that there is an increase in control rates over the location where the tumor was, when SRS is used.
What to expect with Malignant Melanoma Metastatic to the Central Nervous System
In the past, the outlook for melanoma patients with brain metastases (BM) was often quite bleak. Before the turn of the century, the average patient would survive only 3 to 4 months after diagnosis, and less than 10% of patients would live past one year.
However, important advances in the field over the past 20 years have dramatically improved patient outcomes. These include significant improvements in radiation therapy for treating brain metastases, as well as systemic therapies for melanoma itself.
In one study, 179 patients with brain metastases secondary to melanoma were treated with a procedure called Stereotactic Radiosurgery (SRS) along with systemic therapy involving immunotherapy (which strengthens or restores the immune system’s ability to fight cancer) or targeted therapy (which targets the changes in cancer cells that help them grow, divide, and spread). These treatments resulted in a one-year survival rate of 50% among patients and a two-year survival rate of 27%.
Doctors now also have various tools available to help predict patient outcomes in individual melanoma cases. These include the Basic Score for Brain Metastases (BSBM), a score index for radiosurgery in brain metastases, and a diagnosis-specific graded prognostic assessment tool for patients with melanoma brain metastases.
Possible Complications When Diagnosed with Malignant Melanoma Metastatic to the Central Nervous System
The spreading of cancer to the central nervous system (CNS) can lead to several complications including seizures, stroke, cognitive issues (problems with thinking, concentrating, or memory), brain bleeding, blockage of fluid within the brain (obstructive hydrocephalus), pressure on the spinal cord, and even death.
Complications of Cancer Spread to CNS:
- Seizures
- Stroke
- Cognitive dysfunction
- Hemorrhage into the brain (brain bleeding)
- Obstructive hydrocephalus (blockage of fluid within the brain)
- Spinal cord compression (pressure on the spinal cord)
- Death
Preventing Malignant Melanoma Metastatic to the Central Nervous System
It’s key that patients and their families understand how to prevent and manage malignant melanoma, a type of skin cancer. This involves teaching about precautions like using sunscreen regularly, which can help lessen the chances of getting melanoma. If someone has already been diagnosed with melanoma and it has spread to their central nervous system (the brain and spinal cord), it’s often incurable. This can be a very difficult conversation to have.
Patients should be informed about the team of healthcare professionals involved in their care – this could include surgeons who specialize in cancer (surgical oncologists), doctors who use radiation to treat cancer (radiation oncologists), and medical doctors who treat cancer using medication (medical oncologists), along with other healthcare professionals. They should know what the aim of the treatment is, what treatment options are available, and any side effects they might experience from the various treatments. This allows them to make informed decisions about their care that align with their personal goals and beliefs. It’s critical that they regularly attend follow-up appointments and take any required surveillance scans to track their condition.
Patients and their families should also be provided with information and resources about end-of-life care. This can help them prepare and understand what support is available during this difficult time.
