American Melanoma Institute · 5 min read
Who gets Merkel cell carcinoma, how to recognize it, how doctors stage it, and how surgery, radiation, and immunotherapy are used.
Merkel cell carcinoma (MCC) is uncommon. About 3,000 people in the United States are diagnosed each year, according to the American Cancer Society, compared with millions who develop basal or squamous cell cancers. It earns attention because it grows quickly and spreads to lymph nodes early, so the weeks between noticing a bump and having it biopsied matter more than with most skin cancers.
The cancer is named for Merkel cells, touch-sensing cells at the base of the epidermis, the skin's outer layer.
Age is the dominant risk factor. About 8 of 10 people with MCC are older than 70, and the disease is very rare before age 50. Men are affected about twice as often as women, and more than 9 of 10 cases occur in White people. Most tumors appear on skin that has had decades of sun, especially the face, neck, and arms.
A weakened immune system raises the risk sharply. Organ transplant recipients, people living with HIV, and people with blood cancers such as chronic lymphocytic leukemia all develop MCC more often than others their age.
MCC usually looks harmless. The typical tumor is a firm, dome-shaped bump, red, pink, or violet, with smooth and shiny skin over it. It seldom hurts. In a study of 195 patients from the University of Washington (Heath and colleagues, Journal of the American Academy of Dermatology, 2008), more than half of the tumors were assumed to be benign when they were biopsied, most often a cyst.
That study produced a memory aid that dermatologists still use:
In the study, 89% of patients had 3 or more of these features. The combination that most concerns doctors is a red or pink bump that grows fast and doesn't hurt.
In 2008, researchers found a previously unknown virus in MCC tumors and named it the Merkel cell polyomavirus. The virus is present in about 8 of 10 MCC tumors.
Most people pick up this virus in childhood, carry it on their skin for life, and never have a symptom. Only very rarely does the viral DNA become inserted into a skin cell in a way that pushes the cell toward cancer. No screening test exists for it.
The virus does have a practical use. Some patients make antibodies against a viral protein, and doctors can measure them in the blood. Antibody levels usually fall after successful treatment, and a rise later can be an early signal of recurrence.
Diagnosis requires a biopsy. Under the microscope, MCC resembles several other cancers made of small blue cells, so the pathologist uses immunohistochemistry, stains that tag particular proteins. A protein called CK20 marks most MCCs.
Staging comes next, and it moves quickly. Because MCC reaches lymph nodes early, a sentinel lymph node biopsy is typically done even when the nodes feel normal. The surgeon injects a tracer near the tumor site, follows it to the first draining node or nodes, and removes them for testing. This is usually performed during the same operation as the tumor removal.
Imaging is also common at diagnosis. The American Cancer Society notes that a PET/CT scan is often preferred for MCC.
The main treatment for the primary tumor is wide local excision, which removes the tumor with a margin of normal skin. Mohs surgery is sometimes used where tissue is scarce, such as on the face.
MCC is unusually sensitive to radiation. Radiation therapy to the tumor site often follows surgery by a few weeks, particularly when the tumor was large, located on the head or neck, removed with close margins, or when the patient is immune suppressed. If lymph nodes contain cancer, doctors treat that area with radiation, with surgical removal of the nodes, or with both.
Chemotherapy shrinks many MCCs, yet the responses tend to be brief. Checkpoint inhibitors, drugs that release a brake on the immune system's T cells, have replaced it as the first choice for advanced disease. About half of patients with advanced MCC respond to these drugs as a first treatment, and many responses last for years.
The FDA has approved 3 drugs for MCC that is metastatic or has recurred and can't be treated with surgery or radiation: avelumab (Bavencio), pembrolizumab (Keytruda), and retifanlimab (Zynyz). The FDA approved retifanlimab in March 2023 after a trial in which 52% of 65 patients had their tumors shrink. Nivolumab (Opdivo) is also used, although it lacks a specific FDA approval for MCC. All are infusions given every 2 to 6 weeks.
Side effects arise when the activated immune system attacks healthy tissue. Rash, fatigue, diarrhea, and thyroid problems are the most frequent. Inflammation of the lungs, liver, or bowel is less common and needs prompt treatment.
Researchers are testing immunotherapy before surgery and after it for earlier-stage MCC. Results so far are mixed, and more data is needed before these approaches become routine.
American Cancer Society figures, based on people diagnosed from 2015 to 2021, show a 5-year relative survival of 79% for MCC confined to the skin, 66% with regional spread, and 31% with distant spread.
Checkups are frequent in the first few years and include skin and lymph node exams, sometimes with scans or the antibody blood test.
