Conditions: Merkel Cell Carcinoma

Merkel cell carcinoma is a rare, aggressive skin cancer that most often appears as a painless, fast-growing lump on sun-exposed skin of older adults.

What is Merkel cell carcinoma?

Merkel cell carcinoma (MCC) is a rare but aggressive type of skin cancer. It is called a "neuroendocrine" cancer because its cells share features with the body's hormone- and nerve-signaling cells. Although uncommon, MCC is important to recognize because it can grow quickly and spread earlier than most other skin cancers.

The cancer is named after Merkel cells, specialized cells in the deepest layer of the outer skin (the epidermis) that act as light-touch sensors, helping the skin sense gentle pressure. MCC tumor cells look and behave much like these cells. Research now suggests that MCC may not actually begin in mature Merkel cells themselves, but more likely in another skin cell, possibly a skin stem cell or an early skin-lineage cell, that takes on Merkel-cell-like features as it becomes cancerous. The exact cell of origin remains an active area of study, but this uncertainty does not change how the disease is diagnosed or treated.

How rare is it, and who is affected?

MCC is uncommon. In the United States, roughly 1 in about 140,000 people is diagnosed each year (approximately 0.7 cases per 100,000 people annually). Rates are considerably higher in sunny regions such as Australia. The number of cases has been rising steadily over the past two decades, largely due to an aging population, greater sun exposure over lifetimes, more people living with weakened immune systems, and improved detection. MCC tends to affect a specific group of people:

• Older adults: most people are over 70 years old at diagnosis; it is uncommon before age 50.

• Men more than women: men are affected somewhat more often.

• Fair-skinned individuals: the great majority of cases occur in people with lighter skin. Darker skin pigmentation appears to be protective.

• People with weakened immune systems: individuals whose immune systems are suppressed are at notably higher risk. This includes organ transplant recipients, people living with HIV, and people with certain blood cancers such as chronic lymphocytic leukemia. In these groups, MCC can occur at younger ages and tends to behave more aggressively.

What causes Merkel cell carcinoma?

Two main forces drive MCC, and often they work together.

• Ultraviolet (UV) light exposure: long-term sun exposure is a major contributor. This is reflected in the fact that MCC usually appears on sun-exposed skin, occurs mostly in fair-skinned people, and is more common closer to the equator. UV light damages the DNA in skin cells and also weakens the skin's local immune defenses.

• Merkel cell polyomavirus (MCPyV): a common virus that most people are exposed to during childhood and carry harmlessly on their skin for life. In about 80% of MCC cases in the United States, pieces of this virus have become permanently inserted into the DNA of the tumor cells, where they switch on proteins that drive cancer growth. Carrying the virus is extremely common and, by itself, does not mean a person will develop MCC; the cancer is a rare event that depends on additional factors.

• A weakened immune system: a healthy immune system normally keeps virus-infected and abnormal cells in check. When immune surveillance is reduced by medications, disease, aging, or UV light, the risk of MCC rises.

Broadly, MCC falls into two overlapping types: a virus-driven form and a UV-driven form. The UV-driven tumors carry many more DNA mutations. Both types are diagnosed and managed similarly.

Where does it occur on the body?

MCC most often develops on skin that receives the most sun. The head and neck are the single most common location, followed by the arms, shoulders, and legs. It can, however, appear anywhere, including areas with less sun exposure such as the trunk, so location alone does not rule the diagnosis in or out. In a small number of cases, MCC is first found in a lymph node without a visible skin tumor.

What does it look like?

MCC is notoriously easy to overlook because it often appears harmless. It usually shows up as a firm, painless, rapidly growing lump that may be skin-colored, pink, red, or purple, often with a shiny surface. It rarely forms an open sore or crust in its early stages. Because it can resemble a harmless cyst, a pimple, or a common non-cancerous bump, the diagnosis is frequently delayed.

Doctors use the memory aid AEIOU to capture the warning features:

• A, Asymptomatic: the lump is usually painless and not tender.

• E, Expanding rapidly: it grows noticeably over weeks to a few months.

• I, Immune suppression: it is more common in people with weakened immunity.

• O, Older than 50 years of age.

• U, UV-exposed skin in a fair-skinned person.

About 9 in 10 people with MCC have at least three of these features. A lump that is red, rapidly growing, and painless fits the typical pattern of this cancer. Because MCC often looks harmless, a new, changing, or unusual skin growth that does not resemble a person's other bumps is the kind of finding that typically leads to a biopsy.

How is it diagnosed?

MCC cannot be diagnosed by appearance alone; a skin biopsy is required. In a biopsy, a small sample of the lump is removed so it can be examined under a microscope by a pathologist. Under the microscope, MCC appears as sheets of small, round, blue-staining cells that are dividing rapidly.

Because these cells can look similar to several other cancers, including a skin spread of small cell lung cancer, lymphoma, and melanoma, pathologists perform special stains called immunohistochemistry. These stains detect specific proteins on the tumor cells. MCC characteristically stains positive for a marker called cytokeratin 20 (often in a distinctive dot-like pattern) and for neuroendocrine markers, while staining negative for a marker called TTF-1 that is typically present in lung cancer. This combination helps confirm the diagnosis and distinguish MCC from its look-alikes.

How is Merkel cell carcinoma staged?

Staging describes how far the cancer has spread. It combines the size of the skin tumor, whether it has reached nearby lymph nodes, and whether it has spread to distant organs. In simple terms:

• Stage I-II: the cancer is confined to the skin (Stage I for smaller tumors, Stage II for larger ones).

• Stage III: the cancer has spread to nearby lymph nodes or the surrounding skin.

• Stage IV: the cancer has spread to distant parts of the body.

Several tools are used to determine the stage:

• Imaging scans: because MCC can spread silently, imaging is commonly used. A whole-body PET/CT scan is often preferred, though CT scans (and, when needed, MRI of the brain) are also used. Scans reveal hidden spread in a meaningful proportion of people who otherwise appear to have disease limited to the skin.

• Sentinel lymph node biopsy: the lymph nodes are the first place MCC tends to spread, and this spread often cannot be felt or seen. A sentinel lymph node biopsy, usually done at the same time as surgery on the skin tumor, identifies and removes the first lymph node or nodes to which the tumor would drain, so they can be checked for microscopic cancer. This is the most reliable way to detect hidden lymph node involvement. Roughly one-third of people who look node-negative are found to have cancer in these nodes, and even people with small, low-risk tumors can have positive nodes. Finding cancer in the sentinel node is one of the strongest predictors of how the disease will behave.

How does it spread?

MCC is aggressive and has a strong tendency to spread. It characteristically spreads in three ways:

• Local recurrence: it can return in or near the original site on the skin.

• Nodal spread: it commonly travels to nearby lymph nodes, often early and without symptoms.

• Distant metastasis: it can spread through the bloodstream to distant organs such as the liver, lung, bone, and brain.

At the time of diagnosis, a substantial minority of patients already have cancer in the lymph nodes, and a smaller proportion have distant spread. This tendency to spread early is a key reason why thorough staging and close follow-up are important features of MCC care.

What is the prognosis and survival by stage?

The outlook for MCC depends heavily on the stage at diagnosis; the earlier it is caught, the better. Survival estimates vary between studies and depend on many individual factors, but general patterns are consistent: people with disease limited to the skin do considerably better than those whose cancer has reached the lymph nodes or distant organs.

As a general guide, reported five-year survival is highest for early, skin-limited (Stage I) disease, lower for larger skin tumors (Stage II), lower still when lymph nodes are involved (Stage III), and lowest when the cancer has spread to distant organs (Stage IV). When looking specifically at deaths caused by MCC, outcomes for early-stage disease are quite favorable. Because MCC often affects older adults, some patients die of unrelated causes, so overall survival numbers can understate how well the cancer itself is controlled.

Other factors beyond stage also influence prognosis, including age, sex, immune status, tumor size, and certain microscopic features. Individual outlook cannot be read off a table alone and is best discussed with the treating team.

Why does ongoing surveillance matter?

Because MCC can come back, and because most recurrences happen within the first three years after treatment, regular follow-up is a central part of care. Surveillance typically includes:

• Regular physical examinations of the skin and lymph nodes, often every few months at first and less frequently over time.

• Imaging scans when indicated, especially in people at higher risk of recurrence.

• Blood tests in some cases, which may include a test for antibodies against the Merkel cell polyomavirus or newer blood-based tests that can signal a recurrence early.

The intensity of follow-up is greater for people with more advanced disease or with risk factors such as a weakened immune system, and monitoring may be eased for those who remain cancer-free after several years. Catching a recurrence early offers the best chance of effective treatment, which is why follow-up visits and attention to any new or changing skin lumps are a central part of surveillance.

Treatment in brief

Treatment is tailored to the stage and to the individual, and is best coordinated by a team with MCC expertise. In general, disease limited to the skin is treated with surgery to remove the tumor, often combined with radiation therapy and with assessment of the lymph nodes. When MCC has spread more widely, immune-based medicines called immune checkpoint inhibitors have become an important treatment and have substantially improved outcomes for many patients. More detail is on the skin cancer treatments page.