September 5, 2023 – You could have heard of the three most typical types of skin cancer – basal cell carcinoma, squamous cell carcinoma and melanoma – but there's a rarer and more deadly form referred to as Merkel cell carcinoma.
The death of popular singer and songwriter Jimmy Buffett, who died of Merkel cell carcinoma on Friday on the age of 76, has brought this way of skin cancer into the highlight. But what exactly is it? What are the warning signs, how is it different from other kinds of skin cancer, and the way does it result in death?
WebMD turned to one among the leading experts on Merkel cell carcinoma for answers: Paul Nghiem, MD, PhD, chair of dermatology on the University of Washington School of Medicine and director of the Skin Oncology Clinical Program on the Fred Hutchinson Cancer Center, each in Seattle. We also enlisted the expertise of Travis Blalock, MD, director of dermatologic surgery, Mohs microsurgery and skin oncology at Emory University School of Medicine in Atlanta.
It is essential to lift awareness about this sort of skin cancer, said Nghiem.
“Besides melanoma, there is another type of skin cancer called squamous cell carcinoma. This is actually the more common form that you hear a lot about. The likelihood of death from this cancer is more than four times higher than with melanoma.”
Blalock agreed: “Merkel cell carcinoma is a rare but sometimes very aggressive form of skin cancer.” About 2,500 cases are reported within the United States every year. The lesions typically appear on the pinnacle, neck, legs and arms, the parts of the body which might be more exposed to the sun.
No obvious cancer
When asked how easy or difficult it's to diagnose Merkel cells, Nghiem replied: “I would say it's impossible for the average person. It's very difficult for an excellent dermatologist. But a good doctor will notice that something unusual is happening and order a biopsy.”
Many people know that a dark-colored lesion can mean melanoma, but recognizing MCC may be tougher. “Merkel cell carcinomas can sometimes present as an inconspicuous, rapidly growing tumor with a red or pink appearance,” Blalock said. “Unlike melanomas, they lack the familiar characteristic color.”
A Merkel lesion on the skin can easily be treated with a Insect bite, a wound, a cyst or a pimpleHowever, Merkel cell carcinoma often grows quickly and is just not tender to the touch.
Note the AEIOU mnemonic:
- A stands for asymptomatic (doesn't hurt)
- E stands for Expanding (rapid growth)
- I stands for immunity (impaired immunity may mean a better risk)
- O stands for over 50 years
- U stands for UV-exposed skin
Approximately 90% of patients with Merkel cell disease have three or more of those aspects.
A viral cause
The reason individuals with weakened immune systems could also be at higher risk is because Merkel cell carcinoma is attributable to a virus in about 80% of cases, which is one other way it differs from other skin cancers. The remaining 20% of cases are related to sun exposure. In many cases, it's the mixture of those two aspects that one way or the other results in Merkel cell carcinoma.
“The virus is crazy because it's found on our normal skin most of the time. So it's a very, very common virus and a very rare type of cancer,” Nghiem said. “It's an unusual combination.”
How sun exposure and the virus interact to cause this cancer is just not yet fully understood. But individuals with darker skin are likely to have a lower risk, and “that tells us clearly that there is an interaction between the sun and this virus,” he added.
The aim is to detect Merkel cell carcinoma and other types of skin cancer earlier, before they'll spread to other parts of the body. More than 50% of Merkel cell patients develop lymph node metastases, and in around 30% the cancer spreads to other organs.
It's complicated
Researchers know that a sophisticated series of steps are required for Merkel cell carcinoma to develop.
“Genetic mutations have to occur, and we understand these quite well now. The DNA of the virus has to get into the cancer cell and be broken down in a very specific way, and that then leads to cancer,” said Nghiem.
That may very well be a silver lining. “If it wasn't so complicated, it would happen a lot more often because basically everyone gets some sun and everyone is exposed to this virus,” he added.
The Skin Cancer Foundation estimates that 1 in 130,000 Americans is diagnosed with Merkel cell carcinoma. In addition to individuals with weakened immune systems, individuals with sun exposure, fair skin and people over 50 are most in danger.
Although relatively rare, the variety of Americans diagnosed with Merkel cell carcinoma is growing “much faster than other cancers, particularly melanoma,” Nghiem said. The aging of the American population, including many who rarely used sun protectionmay very well be behind the rise in cases, explains the American Academy of Dermatology on its website.
Merkel cell carcinomas often spread to other parts of the body in the event that they will not be detected early enough. For example, if the carcinoma occurs on the pinnacle or neck, it often spreads to the liver. Merkel cell lesions on the legs and other parts of the body typically spread to the lymph nodes within the intestinal area.
If a biopsy shows evidence of this rare cancer, it is best to consider going to one among a couple of dozen specialty centers across the country, Nghiem advises.
“There is clear evidence that the chances of survival are better if you go to a center that is familiar with the treatment.” The website Merkelcell.org offers a nationwide list of specialists.
Although the cancer is comparatively rare, “it's really important to be carefully monitored if you've had other skin cancers before and are immunosuppressed, for example, after an organ transplant,” Nghiem said. “Not just because of that, but for all skin cancers.” In individuals with lifelong immunosuppression, the danger of Merkel cell carcinoma increases 30-fold, he added.
Newer therapy offers hope
If Merkel cell carcinoma is detected early enough before it spreads to other parts of the body, it will probably often be treated successfully.
Another tip is to ensure that your doctor suggests radiation treatment. Unlike many cancers that “grow into a ball” that may be removed with surgery, Merkel cell carcinoma spreads locally and widely throughout the body, which is named “microscopic spread.” Therefore, radiation is a preferred treatment in lots of cases because it will probably treat a bigger area than surgery. In addition, radiation is more practical at killing tumor cells in Merkel cell carcinoma than in another cancers.
A more moderen treatment strategy, immunotherapy, is a more targeted treatment based on an individual's individual genetic mutations. It could also be more practical than traditional treatments similar to chemotherapy, because chemotherapy tends to shut down the immune system, which in turn increases the danger of Merkel cell carcinoma.
“Immunotherapy makes a huge difference. The chance of survival is now about ten times higher,” said Nghiem.
The multi-year survival rate has increased from about 5% to about 50% today, he said. The American Cancer Society offers estimates for 5-year survivalwhich vary depending on whether the cancer is localized or has spread throughout the body.
The improved survival rates would have been unlikely without research support from the National Institutes of Health and the National Cancer Institute, Nghiem said. “It has made a big difference, and it's important for the public to know that.”
For rare diseases like these and lots of others, state and national funding is particularly vital. Although a rare disease affects relatively few Americans, together they account for about 40% of all diseases. He added, “When you look at the big picture, they're a big deal.”
Blalock said he has seen significant advances within the diagnosis and treatment of this “extremely dangerous type of cancer” during his profession as a dermatologist. “These developments have enabled us to intervene effectively and improve the quality of life of patients who in the past faced a serious prognosis,” he said.