Merkel Cell Carcinoma: A Plain-Language Guide

Merkel cell carcinoma was first described by Toker in 1972 as trabecular carcinoma of the skin. NCI calls it an aggressive neuroendocrine carcinoma that arises at the dermoepidermal junction, the boundary between the outer and middle layers of skin, and 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, which NCI attributes partly to better pathology tools and awareness, partly to an aging population, and partly to 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 look like nothing much: a firm, painless, dome-shaped lump in the skin, colored anywhere from faintly pink to deep purple. Ulceration is rare. NCI notes plainly that because the appearance is nonspecific, Merkel cell carcinoma is rarely suspected before the biopsy comes back.

Researchers proposed a mnemonic, 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 is distinguishing Merkel cell carcinoma from several tumors that look nearly identical: small cell lung carcinoma that has spread to skin, lymphoma, peripheral primitive neuroectodermal tumor, metastatic carcinoid, and small cell melanoma.

Two features do the work. On electron microscopy, dense-core cytoplasmic neurosecretory granules. On immunohistochemistry, a stain for cytokeratin-20, which is characteristically positive in Merkel cell carcinoma and negative in small cell lung cancer. Ask whether a stain panel was run, not just a single marker.

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, and whether distant spread is present. NCI lists exactly those five items as the minimum needed to stage anyone.

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 are switched on permanently and drive growth.

The practical consequence is immunological. People who mount a stronger immune response to the virus tend to do better, and that observation is the rationale for treating advanced disease with checkpoint inhibitors rather than chemotherapy.

One-third of patients with no palpable and no radiologically visible nodes turn out to have microscopic cancer in regional nodes. CT alone is not reassurance: in one series CT scans had an 80% false-negative rate for regional spread.

That is why sentinel lymph node biopsy, which maps and removes the first node the tumor drains into, is done at the same operation as the wide excision, while the lymphatic channels are still intact. NCI describes sentinel node biopsy as a way to tell local from regional disease at presentation, and notes that node positivity may be substantially lower for tumors 1.0 cm or smaller. Ask your surgeon whether it is planned in your case.

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

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 JAVELIN Merkel 200, given by vein every 2 weeks in 88 people who had already had chemotherapy. The response rate was 33%, complete responses 11%, median time to response 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 stage IIIB or stage IV disease. 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, produced an overall response rate of 53.5% in 101 previously untreated people, with a median duration of response of 25.3 months. FDA granted accelerated approval in 2023.

The pattern across all three is the same: response rates similar to old chemotherapy, but responses that last far 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 distant lymph nodes as the most common site at 60.1%, then distant skin at 30.3%, lung at 23.4%, central nervous system at 18.4%, and bone at 15.2%. In the same pooled series, 55.5% of patients had lymph node involvement at diagnosis or later.

Because small cell lung cancer can look identical under the microscope, a CT of the chest and abdomen is often done specifically to rule out a lung primary. 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