What is Merkel Cell Carcinoma?

Jimmy Buffett, the popular singer-songwriter who popularized the island escapism genre of music, died on September 1, 2023 at the age of 76. The cause of death was complications from Merkel Cell Carcinoma (MCC) which was diagnosed 4 years ago.

Merkel cell carcinoma (MCC) is a rare type of skin cancer that often appears as a fast-growing, painless nodule on your skin. It generally develops on sun-exposed areas of your skin, like your face, neck, or arms. The nodules might be red or violet and are often firm to the touch. This type of cancer is thought to arise in the Merkel cells in the skin, which are tactile (touch) receptor cells found in the top layer of the skin near the nerve endings that receive the sensation of fine touch and pressure.

MCC is considered to be more aggressive than other types of skin cancer, as it tends to grow quickly and spread (metastasize) to other parts of the body, including the lymph nodes. Its aggressive nature makes early detection and treatment critical. Although less common than melanoma, it is viewed as more deadly.

MCC is quite rare with an estimated annual incidence of about 0.5 cases per 100,000 people in the United States. This compares to an incidence rate of approximately 20 cases per 100,000 people annually for melanoma. 

Like most cancers, the precise causes (etiology) of MCC are not fully understood, but risk factors include:

• Age: Older adults are more likely to develop MCC, although it can occur at any age.
• Sun Exposure: Prolonged exposure to sunlight or other sources of ultraviolet (UV) radiation can increase the risk of MCC.
• Weakened Immune System: People with weakened immune systems, whether due to underlying health conditions or medications, are at a higher risk of developing MCC.
• Merkel Cell Polyomavirus (MCV): Some cases of MCC are associated with this virus, although not everyone with the virus develops MCC.

The last risk factor has drawn attention because it may open the door to new treatment strategies targeting the virus. Researchers have found that roughly eight in 10 MCC tumors are infected with MCV, and many also have the virus DNA integrated into their genome. As a result, MCV proteins such as the oncoprotein Large T antigen are stably expressed by the tumor cells. These MCC cells when grown in tissue culture can be shown to require MCV Large T antigen for growth and proliferation (link). 

But this correlation should be taken with a grain of salt given that approximately 80% of adults in the U.S. have been infected by MCV and are seropositive. In addition, it is not known to what extent the Merkel Cells in seropositive subjects have been infected by the virus. The rare nature of the cancer means that the vast majority of MCV infecteds never develop the cancer. An important check would be to assess among the MCV-infected population the proportion that have the MCV DNA integrated into the Merkel Cell genome and express Large T antigen.

Merkel cell carcinoma possesses a distinctive appearance on the skin presenting as a painless flesh-colored or bluish-red nodule, often on your face, head or neck. Compared to melanoma and other skin cancer types, MCC has more of a raised profile (Figure 1).

Diagnosing Merkel cell carcinoma involves a physical examination and biopsy of the suspicious area to examine the cells under a microscope, as well as testing for characteristic protein biomarkers.

Treatment for MCC includes surgery to remove the tumor, radiation therapy, and/or chemotherapy. In recent years, immunotherapies that help the immune system fight the cancer have also been used to treat MCC, as they have had success against melanoma (QH). Early surgical removal leads to the best possible prognosis.

Figure 1. Comparing a Merkel Cell Carcinoma (MCC) nodule to other skin cancer types. MCC has more of a raised appearance.