Melanoma spread: How lymph nodes play a role in detection

By Jessica Saenz

As one of the body's front-line defense networks and a crucial part of the immune system, the lymphatic system is the first to know about most threats. The lymphatic system moves fluid throughout the body via tiny vessels. These vessels carry bacteria, viruses and other foreign bodies into the lymph nodes to be filtered, trapped or identified as foreign and destroyed.

But when aggressive cancer cells start to spread, this highway of vessels just under the skin becomes the form of transportation that cancer cells take to the nearest organ — often the lymph nodes. Because of this, lymph node biopsies have helped detect the early spread of certain types of cancer, including melanoma, for decades.

Health care professionals continue to rely on lymph node biopsies as they look for new and improved ways to detect the spread of melanoma sooner.

Here's what you should know about this procedure and how cancer experts are working to improve it:

Before a biopsy, your health care professional must find the sentinel lymph node.

"Metastasized melanoma, or melanoma that spreads, classically attacks when it goes deeper into the skin. It burrows, gains access to the lymphatic channels and fires off cells into the stream of the lymphatic flow," says Svetomir Markovic, M.D., Ph.D., a Mayo Clinic medical oncologist and cancer researcher.

But not just any lymph node can be biopsied to find evidence of melanoma spread. When melanoma cells drain into the lymphatic vessels, their first stop is usually the lymph node closest to the site of the melanoma. This is known as the sentinel lymph node.

Most bacteria, viruses and other foreign bodies are destroyed in the lymph nodes, but melanoma cells work to outsmart the immune system and avoid detection.

"Melanoma produces molecules that enter the lymph ahead of the metastasis and try to mask the ability of the lymph nodes to recognize a cancer," says Dr. Markovic. "We believe that this may be one of the reasons that we can see the metastasis in biopsy. Otherwise, it would have been destroyed."

By injecting radioactive material near the site of the melanoma, your health care professional can track the path of drainage and find the lymph node that melanoma cells would have likely reached first. This lymph node, and sometimes nearby lymph nodes, are removed through a surgery called a sentinel lymph node biopsy.

The nodes are then carefully examined for traces of cancer cells. If cancer cells are present, your health care professional might recommend removing the remaining lymph nodes in the area with a procedure called a complete lymph node dissection. Though a complete lymph node dissection has been the standard, many health care organizations — including Mayo Clinic — are now opting for enhanced surveillance and therapy, instead of additional surgery.

Not everyone needs a sentinel lymph node biopsy, but it's advised if melanoma spread is suspected.

When melanoma is caught sooner, it's often thinner. If this is the case, your health care professional might decide that surgically removing the melanoma tumor and tissue around it is enough to avoid melanoma recurrence.

"If it's very superficial, the likelihood of it going into the lymph nodes is negligible, so we normally don't biopsy the lymph node. But if it has an intermediate thickness, we don't know how it's going to behave," says Dr. Markovic.

"Once the melanoma gets to a certain depth, typically greater than 1 millimeter — about the thickness of a dime — it has access to lymphatics and blood vessels," says James Jakub, M.D., a Mayo Clinic surgical oncologist. "Typically, we would then do a sentinel lymph node biopsy at the time of surgical removal to have the pathologist really interrogate those first couple nodes."

Your health care professional can measure the thickness of the melanoma when the tumor is biopsied, or when it is surgically removed, and decide if a sentinel lymph node biopsy is necessary.

A sentinel lymph node biopsy's findings can help guide your care.

While a lymph node biopsy removes some cancer in the process, its main objective is not to treat your melanoma. "This is not a therapeutic procedure," says Dr. Markovic. "This essentially tells us if we need to do more, or not."

In general, when melanoma spreads to the lymph nodes, it's assumed to be more aggressive, which can alter the course of your treatment and help your health care professional choose the right therapies for you.

"The status of the lymph node is very important as far as gauging the risk of the cancer coming back," says Dr. Markovic. "The idea is that if it's metastasized to the lymph node, we know that this is a more aggressive disease. If it wasn't strong enough to burrow deeply and make it all the way to the lymph node, then we infer that it is a less aggressive disease."

When melanoma is aggressive enough to make its way into the lymph nodes, it's reasonable to assume that the spread hasn't stopped there. "At that point, we would consider treatment in carefully selected patients because the risk of having the melanoma appear in the lungs, brain or liver is so high" says Dr. Markovic.

To begin tackling spread, your health care professional might try to identify gene mutations in your melanoma that can help them learn what drugs would be most effective. In patients with certain genetic mutations, these targeted drug therapies can help shrink or slow melanoma spread.

Another treatment option your health care professional might explore with you is called immunotherapy. This form of therapy activates your body's immune system to help fight melanoma.

"Most of the immunotherapy drugs that we use are what we call 'immune checkpoint inhibitors,'" says Dr. Markovic. "These are largely antibodies that are used to 'turn up the volume' on the immune system — high enough to destroy the cancer."

Learning that your melanoma has spread can be jarring, but Drs. Markovic and Jakub reassure patients that treatment and progress toward a cure for melanoma, even in later stages, has come further than ever over the past decade.

"These drugs have been a game-changer in our field over the last 10 years," says Dr. Markovic. "A patient with metastatic melanoma in the year 2000 had an average life expectancy of somewhere between nine and 12 months. Today, it is certainly beyond three years, and it has a decent chance of having a cure."

Complete lymph node dissection carries risks.

All invasive surgeries carry some risk, so it's important to talk to your health care professional about your concerns. You also should also ask your health care professional what to expect after surgery and how you can minimize short and long-term complications.

A common concern patients have, says Dr. Jakub, is that removal of lymph nodes for biopsy can weaken the immune system. "I tell patients, 'You have approximately 600 lymph nodes in your body, so if we take one or a few from a certain area, your body's immune system is certainly not going to miss them," he says.

There can, however, be local effects to the area of the body closest to the site of the lymph node removal. One of these complications includes lymphedema, a swelling of tissue caused by an accumulation of fluid that would normally be drained through your lymphatic system.

"One of the fears and concerns around lymph node surgery is lymphedema, which is very valid," says Dr. Jakub. The risk of lymphedema can vary by location of the lymph nodes removed and the extent of lymph node removal. A complete lymph node resection carries the highest risk — 20% to 40% — and a sentinel lymph node biopsy carries the lowest risk — about 5%.

Lymphedema can be managed when it occurs. Massage therapy, compression sleeves and guidance from a lymphedema therapist can improve lymphedema symptoms. In some cases, surgical options like a lymphovenous bypass can restore the body's ability to drain lymphatic fluid.

Though options are available to manage lymphedema, Dr. Jakub emphasizes that exercise and a healthy lifestyle can reduce the risk of lymphedema occurring in the first place. "An active lifestyle decreases the risk of lymphedema, and I think that's important for patients to know," he says. "People who are obese, sedentary or don't use the extremity are at a much higher risk of lymphedema. There are patients who are afraid to do things, thinking it's going to cause lymphedema when, for the most part, it's the opposite."

Cancer experts are exploring ways to improve or avoid surgical biopsy for melanoma.

Currently, a sentinel lymph node biopsy is the only way to confirm melanoma spread. "Even a PET (positron emission tomography) scan or an MRI can't replace a microscope," says Dr. Jakub. "When disease is too small to see by any other measure, we're kind of stuck."

While there's no substitute for the visual evidence a microscope can provide, cancer experts are exploring ways to reduce unnecessary surgical biopsies by identifying low-risk melanoma cases.

"There's ongoing research at Mayo Clinic, led by Dr. Alexander Meves and Dr. Tina Hieken, that looks at gene expressions of melanoma to tell us if the patient is likely to have a positive node, or if the likelihood of a positive node is so low that it's not worth the risk of surgery," says Dr. Jakub.

Even when a sentinel lymph node biopsy can't be avoided, and the lymph node confirms melanoma spread, complete removal of the surrounding lymph nodes may no longer be necessary in every case. Dr. Jakub says this less-aggressive surgical approach is possible, thanks to treatments like immunotherapy, which are effective at unleashing the immune system to attack cancer cells anywhere in the body. This includes the lymph nodes.

"With a sentinel lymph node biopsy, in the past if we found that any of the first lymph nodes had cancer, we cleared out the rest of the lymph nodes. But if the first couple were negative, we could avoid that in the bulk of patients," says Dr. Jakub. "Now, even if we find cancer in those first lymph nodes, we often don't have to go back and do a lymph node dissection. That's been a major change in our practice within the past two years."

Cancer experts also are using minimally invasive techniques to remove the lymph nodes in patients when melanoma has spread to the lymph nodes near the groin and pelvic area, and they are in the early stages of investigating its use for under arm lymph node biopsies.


Lymph nodes play a big role in the body and in cancer care. And even as other methods of detecting melanoma spread are developed, Dr. Jakub thinks the lymph system will continue to help cancer experts understand effective and individualized treatment for melanoma. "We are finding really high response rates to specific drugs. I see a future where we biopsy a lymph node — without removing it — and identify what therapy the melanoma will be responsive to," he says.

The more cancer experts can learn from a lone sentinel node, the more healthy lymph nodes can be spared. And fewer surgeries can mean less risk and lower costs for patients.

"I think we're going to be doing less and less lymph node dissections," says Dr. Jakub. "Not just for patients who have a tiny bit of cancer in the lymph node, but for patients with a large amount of cancer, and that is certainly exciting."

Learn more

Learn more about melanoma and find a melanoma clinical trial at Mayo Clinic.

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