Neuroendocrine Carcinoma of the Skin
Neuroendocrine carcinoma of the skin is a rare and aggressive type of skin cancer that most often appears as a rapidly growing bump on sun-exposed areas of the body, particularly in older adults.
Table of contents
- What is Neuroendocrine Carcinoma of the Skin?
- Other Names for This Cancer
- Who Gets This Cancer?
- Causes and Risk Factors
- Signs and Symptoms
- How is it Diagnosed?
- How Does This Cancer Behave?
- Treatment Approaches
Merkel cell carcinoma, MCC, trabecular cancer
C44.3; C44.6; C44.7
What is Neuroendocrine Carcinoma of the Skin?
Neuroendocrine carcinoma of the skin is a very rare type of skin cancer. It is also called Merkel cell carcinoma or MCC[1][3]. This cancer forms when cells in the top layer of the skin called Merkel cells grow out of control. Merkel cells are found deep in the outer layer of skin and are connected to nerve endings that help us feel touch[11].
This cancer is aggressive, meaning it tends to grow quickly and spread to other parts of the body[3][10]. Most neuroendocrine carcinomas of the skin are cancerous, and they can spread first to nearby lymph nodes and then to other organs[6].
Neuroendocrine carcinoma of the skin accounts for less than 1% of all skin cancers, but it is the second most common cause of skin cancer death after melanoma[4][6].
Other Names for This Cancer
This cancer is known by several names. Doctors may call it Merkel cell carcinoma (MCC), neuroendocrine carcinoma of the skin, or trabecular cancer[3][11]. All these names refer to the same disease.
Who Gets This Cancer?
Neuroendocrine carcinoma of the skin usually occurs in older people. Most people who are diagnosed are over 50 years old, with the average age being between 50 and 60 years[3][10]. The disease is rare in children, teenagers, and young adults.
This cancer is more common in fair-skinned people, particularly those who are White[4][11]. Men are affected more often than women[10].
The number of people diagnosed with this cancer has been increasing over the last few decades. This increase is likely due to improved diagnostic tests that can identify the disease more quickly[4].
Causes and Risk Factors
While researchers don’t know exactly what causes neuroendocrine carcinoma of the skin, they have identified several factors that increase the risk of developing this cancer.
Sun exposure is a major risk factor. Being exposed to a lot of natural sunlight over your lifetime increases your risk[11]. The cancer most often appears on areas of skin that get regular sun exposure, such as the face, head, neck, arms, and legs[3][11]. Artificial sunlight from tanning beds or certain medical treatments can also increase risk[11].
A weakened immune system is another important risk factor. People whose immune systems don’t work properly are at higher risk. This includes people who have received organ transplants and take medicines that suppress their immune system, people with HIV infection, or those with blood cancers like chronic lymphocytic leukemia[4][11]. About 10% of people with this cancer have weakened immune systems[4].
Merkel cell polyomavirus (MCPyV) plays a role in causing most cases of this cancer. This virus is found in about 80% of neuroendocrine carcinomas of the skin[4][10]. The virus integrates into the DNA of skin cells and causes changes that lead to cancer. However, this virus is common in the general population, and only in very rare cases does it cause cancer.
Other risk factors include having a history of other types of cancer, being older than 50 years, and being male or White[11].
Signs and Symptoms
The first sign of neuroendocrine carcinoma of the skin is usually a single growth or bump on the skin[3][11]. This bump typically has several characteristics that can help identify it.
The growth is usually painless and appears on sun-exposed skin, most commonly on the head, neck, face, arms, or legs[3][9]. In White people, it most often appears on the head or neck, while in Black people, it more commonly appears on the legs[3].
The bump typically grows quickly, sometimes over just a few weeks[9][10]. It is usually firm and may be dome-shaped or raised. The color can vary – it may look pink, red, purple, red-brown, or the same color as the surrounding skin[3][11].
Some people notice that the bump bleeds easily after minor injury, such as when washing the skin or shaving[3].
It’s important to see a healthcare professional if you notice any new growth on your skin, especially if it grows quickly or changes in size, shape, or color[3].
How is it Diagnosed?
Diagnosing neuroendocrine carcinoma of the skin requires several steps. A skin biopsy is necessary to confirm the diagnosis[4][10]. During a biopsy, a doctor removes a small piece of the suspicious skin growth so it can be examined under a microscope.
When pathologists examine the tissue under a microscope, they look for specific features. The cancer cells typically appear as small, blue-colored cells packed together in the deeper layers of the skin. These cells have a distinctive “salt and pepper” pattern in their centers[4].
Additional tests called immunohistochemistry are performed on the biopsy sample. These tests look for specific proteins that help confirm the diagnosis. More than 90% of these cancers show a characteristic dot-like pattern when tested for a protein called cytokeratin 20[4]. The cells also typically test positive for markers of neuroendocrine cells, such as synaptophysin and chromogranin[4][6].
Once the diagnosis is confirmed, additional tests are done to determine if the cancer has spread beyond the skin. These may include ultrasound of nearby lymph nodes and whole-body imaging scans, such as a positron emission tomography (PET) scan[4]. A procedure called sentinel lymph node biopsy is recommended for all patients to check if the cancer has spread to nearby lymph nodes[10][11].
How Does This Cancer Behave?
Neuroendocrine carcinoma of the skin is known for being aggressive. It tends to grow quickly and spread to other parts of the body at an early stage[11].
About one-third of patients already have cancer that has spread to lymph nodes or distant organs at the time of diagnosis[4]. The cancer usually spreads first to nearby lymph nodes. From there, it can spread through the bloodstream to distant parts of the body, including the skin in other areas, lungs, brain, bones, or other organs[11].
According to research studies, up to 40% of tumors come back in the same area after treatment, 55% spread to regional lymph nodes, and 36% spread to distant organs[6]. The length of time people are followed after treatment affects these numbers.
Despite its aggressive nature, survival rates have been improving. The overall two-year survival rate is about 72%, though this varies between males (58%) and females (79%)[6]. With early diagnosis and appropriate treatment, many people can live for years with this cancer.
Treatment Approaches
Treatment for neuroendocrine carcinoma of the skin depends on whether the cancer is limited to the skin or has spread to other parts of the body.
For cancer that has not spread, the main treatment is surgery. Doctors perform a wide local excision, which means removing the tumor along with a margin of healthy skin around it[10][11]. This helps ensure that all cancer cells are removed.
Along with removing the primary tumor, doctors typically perform a sentinel lymph node biopsy or, if cancer has already been found in lymph nodes, a therapeutic lymph node dissection[10][11].
Radiation therapy may be used after surgery to reduce the chance of the cancer coming back. This treatment uses high-energy rays to kill any remaining cancer cells[11].
For cancer that has spread to distant parts of the body, treatment may include immune checkpoint inhibitors. These are newer medicines that help the body’s immune system fight the cancer[10][11]. Some studies are exploring the use of these medicines before surgery (called neoadjuvant therapy) to shrink tumors[10].
An emerging tool for monitoring patients after initial treatment is circulating tumor DNA (ctDNA), which looks for traces of cancer cells in the blood[10].
Each patient’s treatment plan is individualized based on the stage of their cancer, their overall health, and other factors. Treatment decisions should be made with a team of healthcare professionals who specialize in treating this type of cancer.
