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 deadlier form called 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 that? What are the warning signs, how is it different from other skin cancers and the way does it cause death?
WebMD turned to one among Merkel cell carcinoma's preeminent experts 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 micrographic surgery and cutaneous oncology at Emory University School of Medicine in Atlanta.
It is vital to lift awareness of any such skin cancer, said Nghiem.
“In addition to melanoma, there is another skin cancer, squamous cell carcinoma, basically the more common ones that you hear a lot about. This cancer is more than four times more likely to kill someone than 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 was to diagnose Merkel cell, Nghiem replied: “For the average person, I would say impossible.” Very difficult for a wonderful dermatologist. But a very good doctor will know something unusual is happening and order a biopsy.”
While many individuals know that a dark lesion can indicate melanoma, detecting MCC might be tougher. “Merkel cell carcinoma can sometimes appear as an inconspicuous, rapidly 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 confused with one Insect bite, a wound, a cyst or a pimple. However, Merkel cell carcinoma often grows quickly and shouldn't be sensitive to the touch.
Consider the AEIOU mnemonic:
- A stands for asymptomatic (doesn't hurt)
- E stands for Expanding (rapidly growing)
- I stand for immunity (compromised immunity can mean higher risk)
- O is over 50 years old
- U stands for UV-exposed skin
About 90% of Merkel cell patients have three or more of those aspects.
A viral cause
The reason individuals with weakened immune systems could also be at higher risk is that Merkel cell carcinoma is brought on by a virus in about 80% of cases. This is one other difference from other forms of skin cancer. The remaining 20% of cases are attributable to sun exposure. In many cases, it's the mixture of those two aspects that in some way results in the Merkel cell.
“The virus is crazy because it's on most of our normal skin most of the time. So it is a very, very common virus and a very rare cancer,” Nghiem said. “It’s an unusual combination.”
How sun exposure and the virus interact to cause this cancer shouldn't be fully understood. But individuals with darker skin are inclined to be at lower risk, and “that shows us clearly that there is an interaction between the sun and this virus,” he added.
The goal 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 about 30% the cancer spreads to other organs.
It's complicated
Researchers know that a sophisticated series of steps must occur for Merkel cell carcinoma to develop.
“Genetic mutations must occur, and we now understand them quite well. The DNA of the virus has to get into the cancer cell and be chopped up in a certain, highly specific way, and then that leads to cancer,” Nghiem said.
That could possibly be a ray of hope. “If it wasn't so complicated, this would be tremendously more common because basically everyone gets some sun and everyone is exposed to this virus,” he added.
The Skin Cancer Foundation estimates as 1 in 130,000 Americans The diagnosis of Merkel cell carcinoma is made. In addition to immunocompromised people, those most in danger include individuals with previous sun exposure, individuals with fair skin and folks over 50.
Although relatively rare, the variety of Americans diagnosed with Merkel cell carcinoma is “growing much faster than other cancers and particularly melanoma,” Nghiem said. The aging of the American population, including many individuals rarely used sunscreencould possibly be liable for the rise in cases, the American Academy of Dermatology says on its website.
Merkel cell carcinoma often spreads to other parts of the body if it shouldn't be detected early enough. For example, if it occurs on the pinnacle or neck, it tends to travel to the liver. Merkel cell lesions on the legs and other parts of the body typically spread to the lymph nodes across the intestines.
If a biopsy shows evidence of this rare cancer, it is best to, if possible, seek treatment at one among a couple of dozen specialty centers across the country, Nghiem suggested.
“There is clear evidence that survival outcomes are better when 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 monitored carefully if you've had other skin cancers and are immunocompromised after an organ transplant, for example,” Nghiem said. “Not just for this, but for all types of skin cancer.” For individuals with lifelong immunosuppression, the chance 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 might be treated successfully in lots of cases.
Another tip is to be sure your doctor recommends radiation treatment. Unlike many cancers that “grow together into a ball” that might be removed with surgery, Merkel cell carcinoma spreads locally and widely throughout the body, often called “microscopic spread.” Therefore, radiation is the popular treatment in lots of cases because it might treat a bigger area than surgery. Radiation also kills the tumor cells in Merkel cell carcinoma more effectively than in another forms of cancer.
A more moderen treatment strategy, immunotherapy, is a more targeted treatment based on an individual's unique genetic mutations. It could also be simpler than traditional treatments reminiscent of chemotherapy because chemotherapy tends to show off the immune system, which in turn increases the chance of Merkel cell carcinoma.
“Immunotherapy makes a big difference. “The chances of survival are about 10 times better now,” Nghiem said.
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 local or has spread throughout the body.
The improved survival rates could be unlikely without research support from the National Institutes of Health and the National Cancer Institute, Nghiem said. “This has made a huge difference and it is important that the public knows this.”
Federal and state funding is especially vital for rare diseases like these and plenty of others. Although a rare disease affects relatively few Americans, together they account for about 40% of illnesses. He added: “If you look at the bigger picture, they are a big deal.”
Blalock said he has seen significant advances within the diagnosis and treatment of this “extremely dangerous cancer” during his profession as a dermatologist. “These developments have enabled us to effectively intervene and improve the quality of life of patients who have historically faced a severe prognosis,” he said.