Neuroendocrine carcinoma of the skin, also known as Merkel cell carcinoma, is a rare and aggressive type of skin cancer that develops from specialized cells beneath the skin’s surface, most often appearing as a fast-growing, painless bump on sun-exposed areas of the body.

Understanding Neuroendocrine Carcinoma of the Skin

Neuroendocrine carcinoma of the skin is more commonly called Merkel cell carcinoma, or MCC for short. This cancer forms when special cells called neuroendocrine cells, which combine features of nerve cells and hormone-producing cells, begin growing out of control in the skin. These cells are normally found in the deepest layer of the skin, very close to nerve endings that help us sense touch.^[3]

Despite being rare, Merkel cell carcinoma is the second most common cause of death from skin cancer, after melanoma. What makes this cancer particularly concerning is its tendency to grow rapidly and spread early to other parts of the body. It usually spreads first to nearby lymph nodes and then may reach distant organs such as the lungs, brain, or bones.^[11]

The disease typically appears as a single, firm bump on the skin that looks pink, purple, red-brown, or sometimes the same color as the surrounding skin. These bumps grow quickly, often over just a few weeks, and are usually painless. Most people don’t realize something is seriously wrong because the bump doesn’t hurt and might be mistaken for a harmless cyst or other benign skin condition.^[3]

How Common Is This Cancer?

Neuroendocrine carcinoma of the skin is considered very rare. It accounts for less than one percent of all skin cancers.^[4] The number of people diagnosed with this cancer has been increasing over the last two decades, though this increase may partly be due to better diagnostic tools that can identify the disease more accurately and quickly.^[4]

The annual incidence rates vary across different regions. In Western countries, anywhere from one person in a million to one person in forty thousand inhabitants develops this cancer each year. These numbers show significant variation between populations and geographic areas.^[4]

This cancer is rare in children, teenagers, and young adults. Most people diagnosed with Merkel cell carcinoma are older than fifty years of age. On average, people are diagnosed between the ages of fifty and sixty, though the disease most often occurs in those over seventy.^[3][10]

Who Is Most at Risk?

Certain groups of people face higher chances of developing neuroendocrine carcinoma of the skin. Understanding these risk factors can help with early detection, though having one or more risk factors doesn’t guarantee someone will develop the disease.

Fair-skinned individuals, particularly those of White or Caucasian background, have a higher risk of developing this cancer. The disease is much less common in people with darker skin tones. Men are affected more often than women, and elderly individuals face greater risk than younger people.^[10][11]

Exposure to ultraviolet light plays a major role in risk. People who have spent significant time in natural sunlight without protection or who have used artificial tanning devices like tanning beds face increased danger. Those who received psoralen and ultraviolet A therapy, called PUVA, for conditions like psoriasis also have elevated risk.^[11]

People with weakened immune systems represent another high-risk group. This includes individuals living with HIV infection, those with chronic lymphocytic leukemia, and people taking medications that suppress the immune system, such as organ transplant recipients. About ten percent of people diagnosed with Merkel cell carcinoma are immunosuppressed.^[4][11]

Having a history of other types of cancer also increases the likelihood of developing this skin cancer. The disease can occur anywhere on the body, but it most commonly develops on areas regularly exposed to sunlight, particularly the head and neck region.^[11]

What Causes Neuroendocrine Carcinoma of the Skin?

The exact cause of why normal skin cells transform into cancerous ones remains not fully understood. However, researchers have made important discoveries about factors that contribute to the development of this disease.

In the majority of cases—about eighty percent—a virus called Merkel cell polyomavirus, or MCPyV, plays a central role. This virus is actually quite common and lives harmlessly on most people’s skin as part of the normal skin flora. However, in very rare circumstances, the virus’s genetic material becomes integrated into a person’s own DNA. During this integration, specific mutations occur in the viral genome that give it cancer-causing properties while making it unable to reproduce normally.^[4][10]

The other twenty percent of Merkel cell carcinomas develop through a different pathway. These cases are related to mutations caused by ultraviolet radiation from sun exposure. The UV light damages important genes in skin cells, particularly genes called TP53 and pRB, which normally help prevent cancer development. When these protective genes are damaged, cells can grow uncontrollably.^[4]

Researchers now believe that regardless of whether the cancer is virus-related or UV-related, the cell that becomes cancerous is most likely an epithelial cell from the outermost layer of skin called the epidermis, rather than the specialized Merkel cells themselves. This is why the cancer is sometimes called neuroendocrine carcinoma rather than “Merkel cell” carcinoma, though both terms refer to the same disease.^[4]

Recognizing the Symptoms

The first and most common symptom of neuroendocrine carcinoma of the skin is the appearance of a growth or bump on the skin. Understanding what to look for can help people seek medical attention early, which significantly improves outcomes.

The typical bump is a single lump that grows quickly, sometimes visibly larger within just weeks. It is usually firm and dome-shaped or raised above the surrounding skin. Most importantly, the bump is painless, which often leads people to delay seeking medical care because they assume something that doesn’t hurt can’t be serious.^[3][9]

The color of the bump can vary. It may appear pink, purple, red-brown, or violaceous (a bluish-purple shade). In some cases, the bump may be flesh-colored or the same color as the surrounding skin, making it harder to notice. The appearance can sometimes be mistaken for a harmless cyst, a benign skin growth, or even an insect bite.^[3][9]

The location where these bumps appear follows a pattern. In more than thirty-five percent of cases, the bump develops on the head and neck region. The arms and shoulders account for more than twenty percent of cases, while the legs and hips represent more than twenty-five percent. About ten percent occur in other areas including the torso, genitals, or inside the mouth or nose. Interestingly, in about ten percent of cases, the primary skin tumor is never found—instead, the cancer is first discovered when it has spread to lymph nodes.^[9]

In White individuals, the growth most commonly appears on the head or neck. In Black individuals, it more often develops on the legs. This difference in location reflects different patterns of sun exposure and other factors between populations.^[3]

Preventing Neuroendocrine Carcinoma of the Skin

While not all cases can be prevented, especially those related to the Merkel cell polyomavirus, there are important steps people can take to reduce their risk of developing this cancer.

The most important preventive measure is protecting your skin from ultraviolet radiation. This means limiting time in direct sunlight, especially during the middle of the day when the sun’s rays are strongest. When outdoors, wearing protective clothing including long sleeves, long pants, and wide-brimmed hats provides physical barriers against UV exposure. Applying broad-spectrum sunscreen with adequate sun protection factor to exposed skin adds another layer of defense.^[11]

Avoiding artificial sources of UV radiation is equally important. This includes staying away from tanning beds and tanning lamps, which emit concentrated UV radiation that damages skin cells. While treatments like PUVA therapy may be necessary for certain medical conditions, discussing the risks and benefits with healthcare providers helps make informed decisions.^[11]

Regular skin examinations play a crucial role in early detection, which, while not prevention, dramatically improves outcomes. People should check their own skin regularly, looking for any new bumps, moles, or spots, especially those that are growing, changing, or don’t match other marks on the body. Annual skin examinations by a healthcare provider or dermatologist allow trained eyes to identify suspicious changes early.^[3]

For people with weakened immune systems due to organ transplants or other conditions, working closely with healthcare providers to monitor skin health becomes especially important. While it may not be possible to change immune-suppressing medications that are medically necessary, increased vigilance for skin changes can lead to earlier diagnosis if cancer does develop.^[11]

How the Cancer Develops in the Body

Understanding what happens inside the body when neuroendocrine carcinoma of the skin develops helps explain why this cancer behaves the way it does and why certain symptoms occur.

At the microscopic level, when doctors examine tissue from these tumors under a microscope, they see a distinctive pattern. The cancer cells appear bluish or basophilic and are densely packed together. These cells have very little cytoplasm (the material surrounding the cell’s nucleus), and their nuclei show a characteristic “salt and pepper” appearance—a speckled pattern of darker and lighter areas. The cells are dividing rapidly, which pathologists can see as a high mitotic rate, meaning many cells are in the process of multiplying.^[4]

The tumor itself is located in the dermis, the middle layer of skin beneath the outermost epidermis. Often the cancer extends even deeper, reaching the subcutaneous tissue (the layer of fat beneath the skin). Importantly, the tumor typically lacks direct connection with the epidermis above it, which helps pathologists distinguish it from other types of skin cancer.^[4]

What makes this cancer particularly dangerous is its behavior once established. Depending on how long patients are followed after diagnosis, studies show that up to forty percent of tumors recur in the same location after treatment. More concerning, fifty-five percent of patients develop spread to regional lymph nodes (the bean-shaped organs that filter fluid from nearby tissues), and thirty-six percent experience distant metastasis to organs far from the original tumor.^[6]

The cancer cells produce and display certain proteins that help doctors confirm the diagnosis. Using special laboratory techniques called immunohistochemistry, pathologists can identify these markers. More than ninety percent of these tumors show a distinctive paranuclear dot-like pattern when stained for a protein called cytokeratin 20. The cells also typically test positive for neuroendocrine markers like synaptophysin and chromogranin, which confirms their neuroendocrine nature.^[4]

The way this cancer spreads follows a fairly predictable pattern. Initially, it may stay confined to the skin. Then it typically spreads through the lymphatic system to nearby lymph nodes. From there, it can reach distant organs through the bloodstream. Common sites for distant spread include the lungs, liver, bones, and brain. This tendency to spread early and aggressively explains why about one-third of patients already have advanced disease at the time of diagnosis.^[11]