Merkel Cell Carcinoma

What is Merkel cell carcinoma?

Merkel cells sit in the deepest part of the epidermis and are involved in light-touch sensation. Merkel cell carcinoma behaves like a cancer of these cells and shares features with nerve-hormone (neuroendocrine) cancers, though its exact cell of origin is debated.

It is much rarer than other skin cancers but more likely to spread. Recurrence after treatment is common, mostly within the first 2 to 3 years, which is why early diagnosis and close follow-up matter.

Signs and symptoms

The typical lesion is:

• A firm, dome-shaped nodule or small plaque
• Red, pink, flesh-colored or bluish-purple, often shiny
• Painless and not tender
• Growing fast over weeks to a few months
• Usually on sun-exposed skin: face, scalp, ears, neck, arms and legs, though it can appear anywhere

Because it is painless and often looks like a cyst, a pimple, a bug bite or a benign growth, it is frequently not recognized at first. Dermatologists use the AEIOU clues:

• Asymptomatic (not painful or tender)
• Expanding rapidly
• Immune suppression
• Older than 50
• Ultraviolet-exposed site on fair skin

Having three or more of these features in a new lump should prompt a biopsy. A swollen lymph node near the lump may be the first sign of spread, and in some people the node is found without any visible skin tumor.

Causes and risk factors

• Merkel cell polyomavirus: a common virus that most adults carry harmlessly on their skin. In most people with MCC, the virus has integrated into the tumor cells' DNA and drives growth.
• Ultraviolet damage: in virus-negative tumors, heavy sun exposure causes the genetic damage instead.
• Weakened immune system: organ transplant recipients, people with HIV, chronic lymphocytic leukemia or on long-term immune-suppressing drugs have a much higher risk and often a worse course.
• Age: most people are over 70.
• Fair skin, and male sex.
• History of other skin cancers, such as squamous cell carcinoma or melanoma.

Merkel cell carcinoma vs other skin cancers

Diagnosis and staging

1. Skin biopsy: under the microscope MCC is a "small blue cell" tumor. Special stains, especially a dot-like pattern of cytokeratin 20 (CK20), confirm it and separate it from lymphoma or lung cancer that has spread to the skin.
2. Lymph node check: for most tumors without obvious node spread, a sentinel lymph node biopsy looks for microscopic spread, which is common even in small tumors.
3. Imaging: PET-CT or CT scans look for spread to distant nodes or organs.
4. Merkel cell polyomavirus antibody test: a blood test at diagnosis; in people who make these antibodies, rising levels later can signal recurrence.

Staging uses tumor size, lymph node involvement and distant spread:

• Stage I and II: confined to the skin
• Stage III: spread to lymph nodes or nearby skin
• Stage IV: spread to distant organs, such as distant skin, lungs, liver, bone or brain

Treatment

Treatment is best planned by a multidisciplinary team experienced with MCC.

• Surgery: wide excision with a margin of normal skin, or Mohs surgery in delicate areas, plus sentinel node biopsy.
• Radiation therapy: MCC is very sensitive to radiation. It is often given to the tumor site and lymph node area after surgery to reduce recurrence, and is used alone when surgery is not possible.
• Immunotherapy: checkpoint inhibitors, including avelumab, pembrolizumab and retifanlimab, help the immune system attack the cancer. They are standard first treatment for advanced or metastatic MCC and produce lasting responses in many people.
• Chemotherapy: was used before immunotherapy; it often shrinks tumors but responses are usually short. It is now reserved for those who cannot have or do not respond to immunotherapy.
• Reducing immune suppression: for transplant patients, doctors may adjust anti-rejection medicines.

Outlook and follow-up

Outlook depends mostly on stage. Small tumors without node involvement have a good chance of cure. Spread to lymph nodes lowers survival, and distant spread is serious, though immunotherapy has improved outcomes considerably.

Follow-up typically includes skin and lymph node checks every 3 to 6 months for the first 2 to 3 years, plus imaging or virus antibody tests, then less often.

Prevention

• Protect skin from the sun with clothing, hats, shade and broad-spectrum sunscreen SPF 30 or higher.
• Avoid tanning beds.
• Check your skin monthly, and have regular skin cancer screening if you are immunosuppressed or have had skin cancer.
• See a doctor quickly about any fast-growing, painless lump.

Frequently asked questions

What does Merkel cell carcinoma look like?

It usually looks like a firm, smooth, shiny bump that is pink, red, flesh-colored or purplish blue. It is painless, often dome-shaped, and grows quickly over a few weeks or months. It is most common on the face, scalp, neck and arms, and can be mistaken for a cyst or pimple.

Is Merkel cell carcinoma curable?

Yes, many people are cured, especially when the cancer is found before it spreads to lymph nodes. Surgery and radiation treat early disease well. Advanced disease is harder to cure, but immunotherapy produces long-lasting control in a substantial share of patients.

How fast does Merkel cell carcinoma spread?

It is one of the faster-growing skin cancers. The lump often grows visibly over weeks, and microscopic spread to nearby lymph nodes is found in a significant share of people at diagnosis, even with small tumors. That is why fast biopsy and sentinel node testing are recommended.

Is Merkel cell carcinoma caused by a virus?

Most cases are linked to Merkel cell polyomavirus, which lives harmlessly on most people's skin. In MCC, the virus becomes part of the tumor cells' DNA. The cancer itself is not contagious. Cases without the virus are caused mainly by sun damage.

Who is most at risk of Merkel cell carcinoma?

People over 70, those with fair skin and heavy lifetime sun exposure, and people with weakened immune systems, such as organ transplant recipients, people with HIV or chronic lymphocytic leukemia, or those on long-term immune-suppressing medicines. It is more common in men.