Merkel Cell Carcinoma: A Plain-Language Guide

This page is for people diagnosed with Merkel cell carcinoma, and their families. It covers how it is found, what causes most cases, how it spreads, and how advanced disease is treated.

Merkel cell carcinoma was first described by Toker in 1972 as trabecular carcinoma of the skin. NCI calls it an aggressive neuroendocrine carcinoma. Neuroendocrine means the cells share features with nerve and hormone-making cells. It starts at the dermoepidermal junction, the boundary between the outer and middle layers of skin. NCI ranks it as the second most common cause of skin cancer death after melanoma.

It is rare. As of 2013 the United States rate was 0.7 cases per 100,000 people a year. That rate nearly doubled between 2000 and 2013. NCI links this to three things:

• Better lab tools and awareness
• An aging population
• More sun exposure

Age matters more here than in most skin cancers. Cases below age 50 are uncommon, and the median age at diagnosis is about 65. Risk is higher in people whose immune systems are suppressed, including those with HIV, blood cancers, or transplant medicines.

Most Merkel cell tumors do not look worrying. They are a single firm, painless lump in the skin, colored anywhere from faintly pink to deep purple. Ulceration (an open sore) is rare. Because the lump looks so ordinary, NCI notes, Merkel cell carcinoma is rarely suspected before the biopsy comes back.

Researchers proposed a memory aid, AEIOU, from a study of 195 patients:

• A is asymptomatic, meaning it does not hurt or itch.
• E is expanding rapidly.
• I is immune suppressed.
• O is older than 50.
• U is on skin that gets ultraviolet light.

In that study 89% of patients met three or more of the five, 52% met four or more, and only 7% met all five.

Location follows sun. NCI lists the head and neck first, then arms and legs, then the trunk. In one SEER series, skin of the face accounted for 26.9% of cases and skin of the upper limb and shoulder 22.0%.

The pathologist (the doctor who examines tissue) must tell Merkel cell carcinoma apart from several tumors that look nearly the same:

• Small cell lung carcinoma that has spread to skin
• Lymphoma
• Peripheral primitive neuroectodermal tumor
• Metastatic carcinoid
• Small cell melanoma

Two lab findings settle it. Under an electron microscope, the cells show dense-core neurosecretory granules, tiny sacs typical of neuroendocrine cells. And a special stain (immunohistochemistry) for cytokeratin-20 is usually positive in Merkel cell carcinoma and negative in small cell lung cancer. Ask whether a stain panel was run, not just a single marker.

NCI lists five items as the minimum needed to stage anyone. The report should state:

• The maximum tumor size in centimeters
• Whether the tumor invades bone, muscle, fascia, or cartilage
• Whether nodes contain cancer
• How node status was determined
• Whether distant spread is present

In 2008 researchers found a previously unknown polyomavirus in Merkel cell tumor tissue. NCI now states that approximately 70% to 80% of United States cases are caused by Merkel cell polyomavirus. In virus-positive tumors, viral proteins called T antigens stay switched on and drive growth.

This matters for treatment. People whose immune systems respond more strongly to the virus tend to do better. That is the reason advanced disease is treated with checkpoint inhibitors, drugs that help the immune system attack cancer, rather than chemotherapy.

One-third of patients whose lymph nodes cannot be felt or seen on scans turn out to have microscopic cancer in nearby nodes. CT alone is not reassurance: in one series CT scans had an 80% false-negative rate for regional spread. That means they missed the spread 80% of the time.

That is why a sentinel lymph node biopsy is done during the same operation as the wide excision (removal of the tumor with a margin of normal skin). This biopsy maps and removes the first node the tumor drains into. It is done while the lymph channels are still intact. NCI describes it as a way to tell local from regional disease at diagnosis. NCI also notes that cancer in the nodes may be much less common for tumors 1.0 cm or smaller. Ask your surgeon whether it is planned in your case.

Recurrence tends to come early. In a series of 237 people who started with local or regional disease, the median time to recurrence was 9 months, and 91% of recurrences happened within 2 years. That shapes how closely follow-up visits are spaced. Cancer staging explains how the stage groups are put together.

NCI states that immune checkpoint inhibitors are the recommended first-line treatment for most patients with advanced Merkel cell carcinoma. Three are described with specific results.

Avelumab, an anti-PD-L1 antibody, was tested in the JAVELIN Merkel 200 trial. It was given by vein every 2 weeks to 88 people who had already had chemotherapy.

• The response rate was 33%, with complete responses in 11%.
• Median time to response was 6.1 weeks, and 74% of responses lasted at least a year.
• Median overall survival was 12.6 months.
• FDA approved it in 2017.

Pembrolizumab was tested as first treatment in 50 people with unresectable (not removable by surgery) stage IIIB or stage IV disease.

• The response rate was 58%, with 30% complete responses.
• Median progression-free survival was 16.8 months, and 3-year overall survival was 59.4%.
• FDA approved it in 2018.

Retifanlimab, given by vein every 4 weeks, was tested in 101 previously untreated people.

• The overall response rate was 53.5%, with a median duration of response of 25.3 months.
• FDA granted accelerated approval in 2023.

In the pembrolizumab trial, NCI notes the response rate was similar to past rates with chemotherapy, but responses lasted longer. Because these drugs release a brake on the immune system, they bring their own risks. Immune-related side effects covers what to watch for and how quickly to report it.

Pooling 18 case series, NCI reports these sites of distant spread:

• Distant lymph nodes, the most common, at 60.1%
• Distant skin at 30.3%
• Lung at 23.4%
• Central nervous system at 18.4%
• Bone at 15.2%

In the same pooled series, 55.5% of patients had lymph node involvement at diagnosis or later.

Small cell lung cancer can look identical under the microscope. So a CT of the chest and abdomen is often done to rule out a cancer that started in the lung. There is no blood tumor marker specific to Merkel cell carcinoma. Melanoma is a useful comparison, since it is the one skin cancer that outranks this one for deaths.

• A firm skin lump has grown noticeably in under 3 months, especially on the face, scalp, or forearm.
• A new lump appears within a few centimeters of a previously treated site, which may be a satellite lesion.
• You feel a firm, fixed lymph node in the neck, armpit, or groin on the same side as an old skin lesion.
• You take immune-suppressing medicine and notice any new, painless, rapidly growing skin nodule.

• https://www.cancer.gov/types/skin/hp/merkel-cell-treatment-pdq
• https://www.cancer.gov/types/skin/patient/merkel-cell-treatment-pdq