Merkel cell carcinoma
Encyclopedia
Merkel cell
Merkel cells or Merkel-Ranvier cells are oval receptor cells found in the skin of vertebrates that have synaptic contacts with somatosensory afferents. They are associated with the sense of light touch discrimination of shapes and textures. They can turn malignant and form the skin tumor known as...
carcinoma (also known as a "Cutaneous apudoma," "Primary neuroendocrine carcinoma of the skin," "Primary small cell carcinoma of the skin," and "Trabecular carcinoma of the skin"
) is a rare and highly aggressive cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
in which malignant
Malignant
Malignancy is the tendency of a medical condition, especially tumors, to become progressively worse and to potentially result in death. Malignancy in cancers is characterized by anaplasia, invasiveness, and metastasis...
cancer cells develop on or just beneath the skin
Skin
-Dermis:The dermis is the layer of skin beneath the epidermis that consists of connective tissue and cushions the body from stress and strain. The dermis is tightly connected to the epidermis by a basement membrane. It also harbors many Mechanoreceptors that provide the sense of touch and heat...
and in hair follicles.
The majority of Merkel cell carcinomas appear to be caused in part by a virus, Merkel cell polyomavirus
Merkel cell polyomavirus
Merkel cell polyomavirus was first described in January 2008. MCV is one of seven known human tumor viruses. It is suspected to cause the majority of cases of Merkel cell carcinoma, a rare but aggressive form of skin cancer. Approximately 80% of Merkel cell carcinoma tumors have been found to be...
or MCV. Direct evidence for this comes from studies showing that inhibition of MCV proteins causes MCV-infected Merkel carcinoma cells to die but has no effect on tumor cells from Merkel cell carcinomas that are not infected with the virus. MCV-uninfected tumors, accounting for ~20% of Merkel cell carcinomas, appear to have a separate and as-yet unknown cause.
This cancer is a type of neuroendocrine tumor, like small cell lung cancer. Once it has metastasized to the lymph nodes, the 5-year survival rate for a patient is about 50 percent. A patient with a small tumor (less than 2 cm) that has not metastasized to the lymph nodes may have a 5-year survival rate of more than 80 percent. Up to half of patients suffer a recurrence.
Merkel cell carcinoma (MCC) occurs most often on the sun-exposed face, head, and neck.
Signs and symptoms
It usually appears as a firm, painless, noduleNodule (medicine)
For use of the term nodule in dermatology, see Nodule In medicine, a nodule refers to a relatively hard, roughly spherical abnormal structure....
, or tumor
Tumor
A tumor or tumour is commonly used as a synonym for a neoplasm that appears enlarged in size. Tumor is not synonymous with cancer...
. These flesh-colored, red, or blue tumors vary in size from 5 mm (less than a quarter of an inch) to more than 5 cm (2 inches). The tumor grows rapidly. About half of all Merkel cell cancers occur on the sun-exposed areas of the head and neck, while one-third begin on the legs, and 15% occur on the arms. The cancer may also begin on other parts of the body, such as the trunk.
From initial onset, Merkel cell cancer metastasizes quickly and spreads to other parts of the body, tending towards the regional lymph nodes. The tumor tends to invade underlying subcutaneous fat
Adipose tissue
In histology, adipose tissue or body fat or fat depot or just fat is loose connective tissue composed of adipocytes. It is technically composed of roughly only 80% fat; fat in its solitary state exists in the liver and muscles. Adipose tissue is derived from lipoblasts...
, fascia
Fascia
A fascia is a layer of fibrous tissue that permeates the human body. A fascia is a connective tissue that surrounds muscles, groups of muscles, blood vessels, and nerves, binding those structures together in much the same manner as plastic wrap can be used to hold the contents of sandwiches...
, and muscle
Muscle
Muscle is a contractile tissue of animals and is derived from the mesodermal layer of embryonic germ cells. Muscle cells contain contractile filaments that move past each other and change the size of the cell. They are classified as skeletal, cardiac, or smooth muscles. Their function is to...
. It can also metastasize to the liver
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
, lungs, brain
Brain
The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...
or bone
Bone
Bones are rigid organs that constitute part of the endoskeleton of vertebrates. They support, and protect the various organs of the body, produce red and white blood cells and store minerals. Bone tissue is a type of dense connective tissue...
s.
Cause
Merkel cell polyomavirus
Merkel cell polyomavirus was first described in January 2008. MCV is one of seven known human tumor viruses. It is suspected to cause the majority of cases of Merkel cell carcinoma, a rare but aggressive form of skin cancer. Approximately 80% of Merkel cell carcinoma tumors have been found to be...
(MCV) is suspected to contribute to the development of the majority of MCChttp://www.tumorvirology.pitt.edu/mcvrsch.html. Approximately 80% of MCC have this virus integrated in a monoclonal
Monoclonal
Monoclonal cells are defined as a group of cells produced from a single ancestral cell by repeated cellular replication. Thus they can be said to form a single "clone". The process of replication can occur in vivo, or may be stimulated in vitro for laboratory manipulations...
pattern http://www.sciencemag.org/cgi/content/abstract/1152586http://www.nytimes.com/2008/01/17/health/research/17cnd-virus.html?ref=health, indicating that the infection was present in a precursor cell before it became cancerous. At least 20% of MCC tumors are not infected with MCV suggesting that MCC may have other causes as well. Polyomavirus
Polyomavirus
Polyomavirus is the sole genus of viruses within the family Polyomaviridæ. Murine polyomavirus was the first polyomavirus discovered by Ludwik Gross in 1953. Subsequently, many polyomaviruses have been found to infect birds and mammals...
es have been known to be cancer viruses in animals since the 1950s http://www.time.com/time/magazine/article/0,9171,864777-3,00.html, but this is the first polyomavirus strongly suspected to cause tumors in humans. Like other tumor viruses, most people who are infected with MCV probably do not develop MCC; it is unknown what other steps are required for cancer to develop. Ultraviolet light (sun) exposure probably contributes to MCC development in a large number of cases and MCC can occur together with other sun exposure-related skin cancers that are not infected with MCV. Intriguingly, most MCV viruses obtained so far from tumors have specific mutations that render the virus uninfectioushttp://www.pnas.org/content/105/42/16272.longhttp://www3.interscience.wiley.com/journal/121664799/abstract. It is unknown whether these mutations result from sun exposure. MCC also occurs more frequently than expected among immunosuppressed patients, such as transplant patients, AIDS patients and elderly persons, indicating that the tumor is under immune controlhttp://www3.interscience.wiley.com/cgi-bin/fulltext/114266344/HTMLSTARThttp://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=18280333.
While MCV is a common human infection http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1000363, MCC patients whose tumors are infected with MCV have higher antibody levels against the virus than similarly infected healthy adultshttp://www3.interscience.wiley.com/journal/122323759/abstract. A recent study of a large MCC patient registry from Finland suggests that persons with MCV-positive MCC tumors have better prognoses than those without MCV infectionhttp://jnci.oxfordjournals.org/cgi/content/abstract/101/13/938. MCV-positive MCC may be a less aggressive form of the disease, but these results also may be due to differences in tumor stage at diagnosis, age of the patient or location of the tumor rather than an intrinsic difference in the severity of the tumors.
Epidemiology
This type of cancer occurs mostly in — though is not restricted to — Caucasians between 60 and 80 years of age. It occurs about twice as often in males as in females. There are roughly 1200 new cases diagnosed a year in the United States, compared to 60,000 new cases of melanomaMelanoma
Melanoma is a malignant tumor of melanocytes. Melanocytes are cells that produce the dark pigment, melanin, which is responsible for the color of skin. They predominantly occur in skin, but are also found in other parts of the body, including the bowel and the eye...
and over 1 million new cases of nonmelanoma skin cancer
Skin cancer
Skin neoplasms are skin growths with differing causes and varying degrees of malignancy. The three most common malignant skin cancers are basal cell cancer, squamous cell cancer, and melanoma, each of which is named after the type of skin cell from which it arises...
. Merkel cell cancer can be mistaken for another cancer like basal cell carcinoma
Basal cell carcinoma
Basal-cell carcinoma is the most common type of skin cancer. It rarely metastasizes or kills. However, because it can cause significant destruction and disfigurement by invading surrounding tissues, it is still considered malignant. Statistically, approximately 3 out of 10 Caucasians may develop a...
, squamous cell carcinoma
Squamous cell carcinoma
Squamous cell carcinoma , occasionally rendered as "squamous-cell carcinoma", is a histologically distinct form of cancer. It arises from the uncontrolled multiplication of malignant cells deriving from epithelium, or showing particular cytological or tissue architectural characteristics of...
, malignant melanoma, lymphoma
Lymphoma
Lymphoma is a cancer in the lymphatic cells of the immune system. Typically, lymphomas present as a solid tumor of lymphoid cells. Treatment might involve chemotherapy and in some cases radiotherapy and/or bone marrow transplantation, and can be curable depending on the histology, type, and stage...
, or small cell carcinoma
Small cell carcinoma
Small cell carcinoma is a type of highly malignant cancer that most commonly arises within the lung, although it can occasionally arise in other body sites, such as the cervix and prostate....
, or may appear to be a benign cyst
Cyst
A cyst is a closed sac, having a distinct membrane and division on the nearby tissue. It may contain air, fluids, or semi-solid material. A collection of pus is called an abscess, not a cyst. Once formed, a cyst could go away on its own or may have to be removed through surgery.- Locations :* Acne...
. Researchers believe that exposure to sunlight
Sunlight
Sunlight, in the broad sense, is the total frequency spectrum of electromagnetic radiation given off by the Sun. On Earth, sunlight is filtered through the Earth's atmosphere, and solar radiation is obvious as daylight when the Sun is above the horizon.When the direct solar radiation is not blocked...
or ultraviolet light may increase a person’s risk of this disease.
Immune suppression can profoundly increase one's risk of developing Merkel cell cancer. According to a recent study in the Lancet, Merkel cell carcinoma occurs 13.4 times more often in people with advanced HIV
HIV
Human immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...
as compared to the general population. Solid organ transplant
Organ transplant
Organ transplantation is the moving of an organ from one body to another or from a donor site on the patient's own body, for the purpose of replacing the recipient's damaged or absent organ. The emerging field of regenerative medicine is allowing scientists and engineers to create organs to be...
recipients have similarly increased risk.
Treatment
Because Merkel cell cancer is uncommon and is difficult to diagnose, patients may want a second opinion about the diagnosis and treatment plan before starting treatment. However, early diagnosis and treatment of Merkel cell cancer are important factors in decreasing the chance of its spreading, after which it is difficult to cure.Surgery
Surgery is usually the first treatment that a patient undergoes for Merkel cell cancer. In appearance although the lesion appears to be a purple-red in color, there is little else to distinguish this skin cancer from other types such as SCC, BCC and melanoma. Its identity usually comes as a surprise after the surgery.It is normal for the tumor
Tumor
A tumor or tumour is commonly used as a synonym for a neoplasm that appears enlarged in size. Tumor is not synonymous with cancer...
to be removed along with a border of healthy tissue surrounding it. This margin does not appear to be as crucial as it is in melanoma, and indeed, it is common for the Merkel cell cancer to return soon after near the operation site.
Using surgery, nearby or regional lymph nodes may also be removed because once the lesion is more than 1 cm, there is a large risk that they will contain cancer cells. Sometimes the doctor performs a sentinel lymph node biopsy
Biopsy
A biopsy is a medical test involving sampling of cells or tissues for examination. It is the medical removal of tissue from a living subject to determine the presence or extent of a disease. The tissue is generally examined under a microscope by a pathologist, and can also be analyzed chemically...
. In this procedure, the doctor injects a dye or radioactive substance near the tumor. This material flows into the first lymph nodes where cancer is likely to spread (the sentinel nodes). These nodes are then removed and checked for cancer cells. This procedure has been demonstrated to be an important prognostic indicator. Results help dictate the use of appropriate adjuvant therapy, if necessary. However, surgery is usually not sufficient to control Merkel cell cancer by itself.
Radiation and chemotherapy
Radiotherapy is a common part of treatment of Merkel cell cancers. The radiotherapy fields used are usually very large to cover large areas of skin because of Merkel cell cancer's unusual behavior in spreading through the skin and spreading to lymph nodes.Adjuvant
Adjuvant
An adjuvant is a pharmacological or immunological agent that modifies the effect of other agents, such as a drug or vaccine, while having few if any direct effects when given by itself...
radiotherapy has been shown to be effective in reducing recurrence and increasing five year survival of patients with Merkel Cell Carcinoma. Patients who present with no metastases and a negative sentinel lymph node biopsy have a good prognosis when treated with surgery and radiotherapy - approximately 90% survival at five years.
Merkel cell cancer that has metastasized may respond to treatment with chemotherapy and/or radiation. This therapy usually does not cure the disease, but can be effective in shrinking the tumor if the tumor is too large to be removed, or is located in a place where removal would be difficult or dangerous.
Sentinel lymph node biopsy
Sentinel lymph node biopsy detects MCC spread in one third of patients whose tumors would have otherwise been clinically and radiologically understaged and who may not have received treatment to the involved node bed. There was a significant benefit of adjuvant nodal therapy, but only when the SLNB was positive. Thus, SLNB is important for both prognosis and therapy and should be performed routinely for patients with MCC. In contrast, computed tomographic scans have poor sensitivity in detecting nodal disease as well as poor specificity in detecting distant disease.Famous people who have had Merkel cell cancer
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- Nobel-prize winning chemist - Lindsay ThompsonLindsay ThompsonLindsay Hamilton Simpson Thompson AO, CMG , Australian Liberal Party politician, was the 40th Premier of Victoria from June 1981 to April 1982...
- Former Premier of Victoria, Australia - Edward Utley - President of GeicoGEICOThe Government Employees Insurance Company is an auto insurance company. It is a wholly owned subsidiary of Berkshire Hathaway that as of 2007 provided coverage for more than 10 million motor vehicles owned by more than 9 million policy holders. GEICO writes private passenger automobile insurance...
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- Jazz-fusion pioneer