September 5, 2023 – You may have heard of the three most common forms of skin cancer – basal cell carcinoma, squamous cell carcinoma and melanoma – but there is a rarer and deadlier form known as Merkel cell carcinoma.
The death of popular singer and songwriter Jimmy Buffett, who died on Friday at the age of 76 from Merkel cell carcinoma, has put this form of skin cancer in the spotlight. But what exactly is it? What are the warning signs, how is it different from other forms of skin cancer and how does it cause death?
WebMD reached out to one of the leading experts on Merkel cell carcinoma for answers: Paul Nghiem, MD, PhD, chairman of dermatology at the University of Washington School of Medicine and director of the Skin Oncology Clinical Program at Fred Hutchinson Cancer Center, both in Seattle. We also enlisted the expertise of Travis Blalock, MD, director of dermatologic surgery, Mohs micrographic surgery and skin oncology at Emory University School of Medicine in Atlanta.
Greater awareness about this type of skin cancer is important, Nghiem said.
“In addition to melanoma, there is another form of skin cancer: squamous cell carcinoma, the most common form that you hear a lot about. The chance that this cancer will kill someone is more than four times greater than with melanoma.”
Blalock agreed: “Merkel cell carcinoma is an uncommon but sometimes very aggressive form of skin cancer.” About 2,500 cases are reported in the United States each year. The lesions usually appear on the head, neck, arms and legs, the parts of the body that are more exposed to the sun.
No obvious cancer
When asked how easy or difficult it is to diagnose Merkel cell, Nghiem replied: “I would say it is impossible for the average person. Very difficult for an excellent dermatologist. But a good doctor will know something unusual is going on and order a biopsy.”
Although many people know that a dark-colored lesion can indicate melanoma, spotting MCC can be more challenging. “Merkel cell carcinoma can sometimes present as an inconspicuous, fast-growing tumor with a red or pink appearance,” Blalock said. “Unlike melanoma, it lacks a known characteristic color.”
A Merkel lesion on the skin can easily be mistaken for a insect bite, a sore, a cyst or a pimple. However, Merkel cell carcinoma usually grows quickly and does not feel tender.
Consider the AEIOU mnemonic:
- A stands for Asymptomatic (does not hurt)
- E stands for Expand (fast growing)
- I is for immunity (reduced immunity can mean higher risk)
- O is for over 50 years old
- U is for UV exposed skin
About 90% of Merkel cell patients have three or more of these factors.
A viral cause
The reason that people with reduced immunity are at greater risk is that Merkel cell carcinoma is caused by a virus in about 80% of cases. That’s another way it differs from other skin cancers. The remaining 20% of cases are related to sun exposure. In many cases, it is the combination of these two factors that somehow leads to Merkel cell.
“The virus is so crazy because it is on our normal skin most of the time. So it is a very common virus and a very rare form of cancer,” Nghiem said. “That’s an unusual combination.”
How sun exposure and the virus work together to cause this cancer is not yet fully understood. But people with darker skin tend to have a lower risk, and “that clearly tells us that there is an interaction between the sun and this virus,” he added.
The goal is to detect Merkel cell carcinoma and other forms of skin cancer earlier, before they have a chance to spread to other parts of the body. More than 50% of Merkel cell patients experience lymph node metastases and about 30% see the cancer spread to other organs.
Researchers know that a complicated series of steps must occur before Merkel cell carcinoma can develop.
“Genetic mutations have to take place, and we now understand this very well. The DNA of the virus has to enter the cancer cell and be chopped up in a certain, very specific way, and then that leads to the cancer,” Nghiem said.
That could be a silver lining. “If it wasn’t so complicated, this would be vastly more common because pretty much everyone gets some sun and everyone is exposed to this virus,” he added.
That is what the Skin Cancer Foundation estimates 1 in 130,000 Americans the diagnosis of Merkel cell carcinoma will be made. In addition to people with weakened immune systems, the people most at risk include people with a history of sun exposure, people with fair skin and people over 50 years of age.
Although relatively rare, the number of Americans diagnosed with Merkel cell carcinoma is “growing much faster than other types of cancer, and melanoma in particular,” Nghiem said. The aging of the US population, including many who are rarely used sun protectioncould be behind the increase in cases, the American Academy of Dermatology says on its website.
Merkel cell carcinoma often spreads to other parts of the body if it is not caught early enough. For example, if it appears on the head or neck, it tends to go to the liver. Merkel cell lesions on the legs and other parts of the body typically spread to the lymph nodes around the intestines.
If a biopsy comes back indicating this rare form of cancer, seek care at one of about a dozen specialty centers across the country, if you can, Nghiem suggested.
“There is clear evidence that survival outcomes are better if you go to a center that knows how to deal with it.” The Merkelcell.org site offers a national list of specialists.
Although the cancer is relatively rare, “if you have had other forms of skin cancer and your immune system is suppressed after an organ transplant, for example, it is very important to be monitored carefully,” Nghiem said. “Not just for this alone, but for all forms of skin cancer.” For people who suppress their immune systems for life, the risk of Merkel cell carcinoma increases 30-fold, he added.
Newer therapy offers hope
If Merkel cell carcinoma is caught early enough, before it spreads to other parts of the body, it can be treated successfully in many cases.
Another tip is to make sure your healthcare provider suggests radiation treatment. Unlike many cancers that “grow into a ball” and can be removed with surgery, Merkel cell carcinoma jumps locally and remotely around the body, known as “microscopic spread.” Radiation therapy is therefore a preferred treatment in many cases, because it can treat a larger area than surgery. Radiation also kills the tumor cells in Merkel cell carcinoma more effectively than in some other types of cancer.
A newer treatment strategy, immunotherapy, is a more targeted treatment based on a person’s unique genetic mutations. It may be more effective than traditional treatments such as chemotherapy because chemotherapy tends to disable the immune system, which again increases the risk of Merkel cell carcinoma.
“Immunotherapy makes a huge difference. The chances of survival are now about ten times greater,” said Nghiem.
Multi-year survival 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 local or has spread throughout the body.
The improved survival rates would be unlikely without research support from the National Institutes of Health and the National Cancer Institute, Nghiem said. “That has made a big difference, and it is important that the public knows that.”
For rare conditions like these and many others, federal and state funding is especially essential. Although a rare condition may affect relatively few Americans, together they make up about 40% of diseases. He added: “If you look at the big picture, they are a big deal.”
Blalock said that during his career in dermatology, he has witnessed significant advances in diagnosing and treating this “extremely dangerous cancer.” “These developments have allowed us to intervene effectively and improve the quality of life of patients who have historically faced a serious prognosis,” he said.