Seattle Multidisciplinary MCC TeamUniversity of Washington MCC ResearchFred Hutchinson Cancer Research Center Seattle Cancer Care Alliance/Skin Cancer

 


What is a Merkel cell?

Merkel cells are found in the skin (see diagram below) where their key function is as touch receptors.

 

Normal Merkel cells within the skin

Normal Merkel cells in the skin: In this illustration of a cross-section of skin, normal Merkel cells are shown in red and connect to nerves shown in yellow. The structures drawn include the epidermis (upper third), dermis (middle), and deeper adipose layer containing the fatty tissue. Arteries are depicted as red and veins are blue.

Figure Copyright by Paul Nghiem, MD, PhD & Quade Medical Group.

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What is Merkel cell carcinoma

Merkel cell carcinoma (MCC), sometimes referred to as a neuroendocrine carcinoma of the skin, arises from the uncontrolled growth of Merkel cells in the skin. It is a rare skin cancer with roughly 1500 cases per year in the United States, making it about 40 times less common than melanoma. MCC has the potential to be lethal, and thus prompt aggressive treatment is warranted.

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Carcinoma skin appearance

MCC does not have a distinctive appearance (see photograph below). It usually develops on sun-exposed skin (e.g., head, neck, arms) as a painless, firm, flesh-colored to red or blue bump. Frequently, patients seek advice from their doctor because the bump is growing rapidly or the overlying skin is breaking down. Most MCCs are diagnosed when a skin biopsy is performed to rule out another sun-induced skin cancer or a cyst. In the vast majority of cases, both the doctor and the patient are surprised by the diagnosis of MCC.

 

Merkel cell carcinoma on the lip of a 92-year-old man (Nghiem, 2001).

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What are the causes?

The exact causes of MCC are not known. Factors strongly associated with the development of MCC are:

  • Age over 65 years
  • Fair skin
  • History of extensive sun exposure
  • Chronic immune suppression (e.g., kidney or heart transplantation or HIV)

The best available information on characteristics of patients with MCC comes from a study of 1,034 patients summarized in the table below (Agelli, 2003). The average (median) age of the patients with MCC was 74 years. The most common sites of involvement were head followed by arms (upper limb). At the time of diagnosis, half of the patients had disease localized to the skin, while the other half had MCC that was no longer confined to the skin.

 

Total Number of Patients = 1034
Median Age (years)                        74
Age groups (years)
No.
(%)
     < 65
247
(23.9)
     65-74
281
(27.2)
     >/= 75
506
(48.9)
Race
No.
(%)
     White
968
(93.6)
     Black
12
(1.2)
     Other
37
(3.6)
     Unknown
17
(1.6)
Anatomic site
No.
(%)
     Head
499
(48.3)
     Trunk
117
(11.3)
     Upper limb
199
(19.3)
     Lower limb
165
(16.0)
     Other
54
(5.2)
Stage at diagnosis
No.
(%)
     Localized
507
(49.0)
     Regional
281
(27.2)
     Distant
81
(7.8)
     Unstaged
165
(16.0)

Patient characteristics. Adapted from Agelli, 2003.

Age & Merkel cell carcinoma

The number of MCC cases increases with advancing age. The average age for developing MCC is 74 years, with 75% of patients over the age of 65 years. The incidence of MCC (see graph below) is somewhat greater in men (squares) than in women (circles) for each age group. Thus, advancing age and male gender are risk factors for MCC.

 

Frequency of MCC by age & sex: men (square) & women (circle). Adapted from Agelli, 2003.

 

 

Sunlight & Merkel cell carcinoma

It is believed that ultraviolet radiation from the sun plays a significant role in the development of MCC (see schematic below). This cancer is found most commonly on sun exposed areas of the body (e.g., head, neck, arms) in older Caucasian individuals, who may also have other sun-induced skin cancers. There is more MCC in sunny climates (Hawaii) as opposed to areas with less sun (Connecticut) (see graph below). Thus, a history of extensive sun exposure is a risk factor for MCC.

 

 

Frequency of MCC of the head in Caucasians by UV exposure (Agelli, 2003)

 

 

Immune function & Merkel cell carcinoma

MCC is associated with a profoundly weakened immune system, such as in patients with HIV/AIDS, in patients who have received an organ transplant who are on medications that suppress the immune system, or people with chronic lymphocytic leukemia (CLL) and certain types of lymphoma. The risk of developing MCC is increased 8-fold in HIV patients (Engles, 2002), 10-fold in organ transplant patients (Penn, 1999), and 34-fold to 48-fold in CLL (Heath, 2008). Long-term suppression of the immune system (for many years) appears to be a risk factor for MCC in some patients. While patients with profound immune suppression are at a higher risk of developing MCC, over 90% of all people who develop MCC in fact have a normal immune system (Heath, 2008). It is sensible to eat well, exercise, and get plenty of sleep to promote good immune health. Although not proven in humans, some complementary medical approaches aim to improve immune function (see “Treatment: Complementary and Alternative” section).

 

A virus is involved in Merkel cell carcinoma


A virus was discovered in 2008 to be frequently involved in MCC. This new virus is called Merkel cell polyomavirus (MCPyV) (Feng, 2008). The virus was found in 8 of 10 tumors tested, and it was associating with the DNA of the tumor cells in such a way to suggest that it is involved in the development of MCC. Several additional studies have validated this study, finding MCPyV in 43 of 53 patients (Becker, 2008) and 7 of 12 patients (Ridd, 2008). Interestingly, in our lab, we found a regional difference in the percentage of tumors having the virus, with 11 of 16 (69%) tumors from North America having the virus and only 5 of 21 (24%) Australian tumor samples testing positive for the virus (Garneski, 2008). The study of this associated polyomavirus is an exciting area of research to help us better understand this cancer. It is an active area of research as to whether virus-negative tumors should be treated differently than virus-positive tumors.              .

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