Merkel Cell Carcinoma: Rare Skin Cancer Guide

Merkel cell carcinoma is a rare skin cancer. It begins in neuroendocrine cells in the outer layer of the skin. These cells sit near nerve endings and take part in the sense of touch.

It is uncommon, but it is aggressive. It tends to grow quickly and to spread early. It is the second most common cause of death from skin cancer after melanoma. That combination — rare and fast-moving — is why it is worth asking about care at a center that sees this cancer regularly.

Most Merkel cell carcinomas appear as a single firm, dome-shaped lump on sun-exposed skin. Usually that is the head, neck, arms or legs. The lump is typically red, pink or violet, and it does not hurt.

Clinicians often use a checklist to remember the warning signs:

• Asymptomatic, meaning painless and not tender
• Expanding rapidly over weeks
• Immune suppression
• Older than 50
• UV-exposed skin in a fair-skinned person

A painless lump is easy to ignore. Rapid growth is the feature that should send you to a dermatologist for a biopsy.

Three factors stand out.

Ultraviolet light. Rates are higher in sunnier regions. They are also higher in people with fair skin that burns easily. Tanning beds and PUVA light therapy raise risk too.

A weakened immune system. Some people are diagnosed more often and can have more aggressive disease. That includes people taking anti-rejection medicines after an organ transplant, people living with HIV, and people with blood cancers such as chronic lymphocytic leukemia.

Merkel cell polyomavirus. This virus is found in many Merkel cell tumors. It also sits harmlessly on the skin of most healthy adults. So infection alone does not cause cancer, and the disease is not catching. Research suggests two routes to this cancer. One is driven by the virus. The other is driven mainly by sun damage built up over years. Which route applies can affect how the tumor behaves and how it is monitored.

Age matters as well. Most people are diagnosed after 50, with a median age around 65. It is slightly more common in men.

Diagnosis starts with a skin biopsy, which means taking a small sample of skin to examine. Merkel cell carcinoma can look like other cancers under the microscope, so pathologists use special stains to confirm it.

Staging usually involves imaging, often a PET-CT. It frequently involves a sentinel lymph node biopsy as well, which samples the first node the cancer would drain to. That last step matters here. This cancer can already be in the lymph nodes without any node being large enough to feel. Knowing whether nodes are involved changes both treatment and follow-up. Stages run from 0 through IV, with stage IV meaning spread to distant sites.

Surgery to remove the tumor with a margin of normal skin is the usual first step for disease that has not spread.

Radiation therapy is often given to the surgical site, and sometimes to the lymph node area. This cancer is sensitive to radiation and tends to come back locally.

Immunotherapy has changed the outlook for advanced disease. Three checkpoint inhibitors are approved: avelumab, pembrolizumab and retifanlimab. They work by releasing a brake on the immune system so it can recognize the tumor. Not everyone responds, but responses can last a long time. These drugs can cause immune-related side effects in the thyroid, bowel, skin, liver or lungs. Those are treatable when reported early.

Chemotherapy can shrink tumors and is still used in some situations. Responses tend to be shorter than with immunotherapy.

If you take immune-suppressing medicine, that has to be part of the conversation. It affects the risk of the cancer coming back, and it affects whether checkpoint immunotherapy is safe for you.

The risk of the cancer coming back is highest in the first two to three years. So visits are frequent at first, usually every three to six months. They include skin and lymph node examinations, plus imaging based on your stage. Some centers use a blood test for antibodies to Merkel cell polyomavirus to help watch for the disease returning.

Between visits, report any new lump, any change in a scar, or any swollen node rather than waiting.

• Call 911 or go to an emergency department if you suddenly cannot get enough air, or your chest hurts, or your heart is racing. Checkpoint drugs can inflame the lungs or the heart muscle.
• Ring your oncology team straight away if your temperature hits 100.4°F (38°C) or higher during treatment. CDC counts a fever in someone on cancer treatment as an emergency, since it can be the only warning of a fast-moving infection. Any hour is the right hour to call. If they cannot be reached quickly, go to an emergency department and mention your treatment.
• Call your care team the same day if you are passing several more watery stools a day than usual, or there is blood in them. Colitis is the immune side effect that turns serious fastest. The same applies to a rash that is spreading or blistering, or new muscle weakness.
• Call your care team within a day or two if you notice a new lump, a firm change in an old scar, or a swollen gland — and do not wait for the next scheduled visit. Also flag deep tiredness or unusual thirst, which can mean the thyroid or pituitary has been affected.

• CDC — Watch Out for Fever (Preventing Infections in People With Cancer)
• NCI: Immune Checkpoint Inhibitors
• NCI: Infection and Neutropenia during Cancer Treatment
• NCI: Merkel Cell Carcinoma Treatment (PDQ®) Health Professional Version
• NCI drug information: avelumab
• NCI drug information: retifanlimab-dlwr
• NCI drug information: pembrolizumab
• NCI: Immunotherapy to Treat Cancer