Merkel cell cancer

Key Terms: Merkel cells, Metastasis.

Definition

Merkel cell carcinoma (MCC) is a rare form of cancer that develops on, or just beneath, the skin and in hair follicles. It is also known as neuroendocrine cancer of the skin or trabecular cancer.

Description

Merkel cells are cells that lie in the middle layers of the skin. They are named for their discoverer, a German professor of anatomy named Friedrich Sigmund Merkel (1845–1919). These cells are organized around hair follicles and are believed to act as some type of touch receptors. MCC begins in these cells.

MCC usually appears as firm shiny skin lumps, or tumors. These tumors are painless and can range in size from less than a quarter of an inch (0.6 cm) to over two inches (5.1 cm) in diameter. They may be red, pink, or blue. Tumors first appear on the head and neck in about 48% of cases, and less frequently on other sun-exposed parts of the body.

MCC is very aggressive, it spreads very rapidly, and it often invades other tissues and organs (metastasizes). The most common sites of metastasis of MCC are the lymph nodes, liver, bones, lungs, and brain. Metastasis to the lymph nodes generally occurs within seven to eight months after the first skin tumors appear. Nearly half of all people affected with MCC will develop systemic metastases within 24 months, and 67% to 74% of these people will die within five years.

Local recurrence of MCC after the removal of the primary tumor occurs in approximately one-third of all patients and is usually apparent within four months.

Several other names have been used to describe MCC, among these are: anaplastic carcinoma of the skin, apudoma, endocrine carcinoma of the skin, neuroendocrine carcinoma of the skin (NEC), primary small-cell carcinoma of the skin, primary undifferentiated carcinoma of the skin, and trabecular cell carcinoma. The two most commonly used names are MCC and NEC.

Demographics

MCC is seen almost exclusively (94% of known cases) in Caucasians. It affects males more often than females. Seventy-six percent of cases reported in the United States have been diagnosed in people older than 65, but MCC has also been seen in a child as young as seven and a woman as old as 97.

As of 2003, the National Cancer Institute (NCI) had compiled records of 1034 patients in the United States diagnosed with MCC. The number of new cases of MCC is expected to rise as the average life span continues to increase, exposure to the sun remains high, and MCC is recognized more often by medical practitioners.

Causes and Symptoms

The cause of MCC has not been positively identified. As of the early 2000s, it is believed to be caused by the skin damage associated with exposure to ultraviolet light from the sun.

Some researchers believe that Merkel cell carcinoma may also be associated with immunodeficiency syndromes, as six of the 1043 patients recorded in the United States developed MCC after being diagnosed with chronic lymphocytic leukemia.

The only symptom of primary MCC is the appearance of the characteristic tumors in the skin. Lymph node metastases show enlarged, firm, lymph nodes in the region of the primary tumor. Other systemic metastases show as masses in the affected organs. The location of the primary tumor is not related to the location of these systemic metastases.

Diagnosis

The diagnosis of MCC is performed by examining and testing a biopsy of the tumor. MCC is difficult to differentiate from several other forms of abnormal tissue growth (neoplasms). This diagnosis cannot be made just by examining the tumor cells under a microscope. It is done by performing a variety of chemical tests on these cells. Testing must be performed to make sure this is not metastatic oat-cell (lung) cancer.

Treatment Team

MCC is generally first identified by a microbiologist who examines a biopsy sample. Most MCC tumor removals are performed by dermatologists. Post-operative radiation treatments are generally ordered by the dermatologist and performed by a radiation therapist under the direction of a radiologist and/or a radiation physicist.

Because of the rapid and possibly invasive nature of MCC, patients are generally referred to a physician specializing in cancer (oncologist) to ensure that the disease has not spread to other parts of the body. Chemotherapy for MCC is considered investigational as of late 2003.

Clinical Staging, Treatments, and Prognosis

MCC is classified into three clinical stages. Stage I MCC is defined as a disease that is localized to the skin. Stage II MCC is characterized by a spreading of the disease to the lymph nodes that are near the primary skin tumor or tumors. Stage III MCC is characterized by systemic metastases.

Treatment of stage I MCC involves wide local excision and follow-up radiation therapy. Wide local excision is a procedure in which the tumor and a small area of the surrounding healthy tissue are surgically removed. Since MCC is so aggressive, all patients are considered to be at high risk for recurrence and metastasis. For this reason, all patients will undergo radiation therapy of the lymph nodes near the site of the primary tumor that was removed. A technique called lymphoscintigraphy is used to determine the precise location of the lymph nodes that are most likely to be affected.

Treatment of stage II MCC is the same as for stage I MCC with the additional removal of the affected lymph nodes.

Treatment of stage III MCC is generally chemotherapy. But, because the number of known cases of MCC is relatively small, there is no generally prescribed chemotherapy regimen. It has been treated with etoposide, cisplatin, and fluorouracil with varying degrees of success.

The prognosis for patients affected with MCC is generally poor. Half will have a recurrence within two years and one-third will develop systemic involvement (stage III). The average time span from diagnosis of stage III MCC to death is eight months. The two-year survival rate for people affected with MCC is approximately 50%. Factors that improve the patient's length of survival include location of the tumor on the limbs rather than the face; localization of the disease; and female sex.

Alternative and Complementary Therapies

Naturopathic remedies believed by some to be beneficial in the prevention of skin cancers include regular cleansing by fasting, enema, or herbal supplements. Many naturopaths also recommend a daily scrubbing of the skin with a sauna brush prior to bathing to increase circulation. Vitamins A, C, and E, as well as zinc, are believed by some to be essential supplements to a high fiber diet in the prevention of skin damage. However, these remedies have not been proven effective in treating Merkel cell tumors. Traditional medical treatments which have succeeded include surgery, radiation therapy, chemotherapy, and rare success with stem cell transplant.

Coping With Cancer Treatment

The radiation therapy necessary for follow-up treatment after MCC tumor removal can become stressful for some patients. Additionally, most of these cancers occur in the head and neck region, and their removal can be very disfiguring. It is important that all patients receive adequate counseling and other psychological support prior to and during such treatments.

Clinical Trials

In late 2003, the National Cancer Institute was conducting three phase II studies of treatments for Merkel cell carcinoma: a study of antineoplaston therapy for MCC; a study of imatinib mesylate, a drug that blocks enzymes necessary for tumor growth; and a study of oblimersen, a drug that blocks the production of a crucial protein in cancer cells.

Prevention

Because MCC is believed, at least in some cases, to be caused by long-term exposure to ultraviolet light, it may possibly prevented by avoiding sun exposure when possible and by wearing a PABA containing sunscreen daily.

Questions to Ask the Doctor

• What stage is my cancer in?
• How long will my radiation therapy treatments last after the tumor is removed?
• What are the possible side effects of the particular radiation or chemotherapy treatments that I will receive?
• How often should I continue to be checked for possible recurrence of MCC?

Special Concerns

MCC is very aggressive and can metastasize quickly. For these reasons, medical treatment needs to be sought quickly when MCC is suspected. Recurrence of MCC, either on the skin or in the lymph nodes or other bodily organs, is quite common. Therefore, it is extremely important that all MCC patients, even if they believe that they have no symptoms, have follow-up examinations monthly for at least two years after they have finished their initial radiation treatments.

Resources

Periodicals

Agelli, M., and L. X. Clegg. "Epidemiology of Primary Merkel Cell Carcinoma in the United States." Journal of the American Academy of Dermatology 49 (November 2003): 832–841.

Khan Durani, B., and W. Hartschuh. "Merkel Cell Carcinoma. Clinical and Histological Differential Diagnosis, Diagnostic Approach and Therapy." [in German] Hautarzt 54 (December 2003): 1171–1176.

Mortier, L., X. Mirabel, C. Fournier, et al. "Radiotherapy Alone for Primary Merkel Cell Carcinoma." Archives of Dermatology 139 (December 2003): 1587–1590.

Poulsen, M., and D. Rischin. "Merkel Cell Carcinoma—Current Therapeutic Options." Expert Opinion in Pharmacotherapy 4 (December 2003): 2187–2192.

Vlad, R., and T. J. Woodlock. "Merkel Cell Carcinoma After Chronic Lymphocytic Leukemia: Case Report and Literature Review." American Journal of Clinical Oncology 26 (December 2003): 531–534.

Organizations

American Academy of Dermatology (AAD). P. O. Box 4014, Schaumburg, IL 60168-4014. (847) 330-0230. Fax: (847) 330-0050. .

American Cancer Society. (800) ACS-2345. >.

The Skin Cancer Foundation. 245 Fifth Ave., Suite #1403, New York, NY 10016. (800) SKIN-490. .

Other

CancerNet: Merkel Cell Cancer. [cited June 27, 2005]. .

Skincancerinfo.com. [cited June 27, 2005]. .

—Paul A. Johnson, Ed.M.; Rebecca J. Frey, Ph.D.

This article is missing citations or needs footnotes. Please help add inline citations to guard against copyright violations and factual inaccuracies. (September 2007)

It has been suggested that Trabecular cancer be merged into this article or section. (Discuss)

Merkel cell cancer
Classification and external resources
Small spot on the left arm is Merkel cell cancer.
ICD-10	C44. (M8247/3)
DiseasesDB	31386
eMedicine	DERM/262 ent/714
MeSH	D015266

Merkel cell carcinoma. Gross pathology specimen.

Merkel cell cancer, also called Merkel cell carcinoma, trabecular cancer, Apudoma of skin, or Small cell neuroepithelial tumor of the skin, is a rare and highly aggressive cancer where malignant cancer cells develop on or just beneath the skin and in hair follicles. The majority of Merkel cell carcinomas appear to be caused by a newly discovered virus, Merkel cell polyomavirus. 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 small tumor (less than 2 cm) that has not metastasized to the lymph nodes reported a 5-year survival rate of more than 90 percent; however, at the time of diagnosis of MCC the 5-year survival was 64 percent. Up to half of patients suffer a recurrence.^[1]

It occurs most often on the face, head, and neck. It usually appears as firm, painless, nodules, or tumors. 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, fascia, and muscle. It can also metastasize to the liver, lungs, brain or bones.

Contents 1 Cause 2 Epidemiology 3 Treatment 3.1 Surgery 3.2 Radiation and chemotherapy 3.3 Sentinel lymph node biopsy 4 Famous people who have had Merkel cell cancer 5 See also 6 References 7 External links

Cause

Merkel cell carcinoma (arrow) infiltrating skin tissue, stained brown for Merkel cell polyomavirus large T protein.[1] Approximately 80% of MCC tumors are infected with MCV.

A newly discovered virus called Merkel cell polyomavirus (MCV) is suspected to contribute to the development of the majority of MCC. Approximately 80% of MCC have this virus integrated in a monoclonal pattern [2][3], 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. Polyomaviruses have been known to be cancer viruses in animals since the 1950s [4], 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.^[2] 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, all MCV viruses obtained so far from tumors have specific mutations that render the virus uninfectious[5][6]. 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 control[7][8].

While MCV is a common human infection [9], MCC patients whose tumors are infected with MCV have higher antibody levels against the virus than similarly infected healthy adults[10]. 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 infection[11]. 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 melanoma and over 1 million new cases of nonmelanoma skin cancer.^[3] Merkel cell cancer can be mistaken for another cancer like basal cell carcinoma, squamous cell carcinoma, malignant melanoma, lymphoma, or small cell carcinoma, or may appear to be a benign cyst. Researchers believe that exposure to sunlight 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 as compared to the general population. Solid organ transplant recipients have similarly increased risk.^{[citation needed]}

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 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. 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 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.^[4]

Famous people who have had Merkel cell cancer

• David Brudnoy Boston talk radio host
• Al Copeland New Orleans Entrepreneur, Powerboat Racer.
• Max Perutz Nobel-prize winning chemist
• Lindsay Thompson Former Premier of Victoria, Australia
• Edward Utley President of Geico
• Joe Zawinul Jazz-Fusion Pioneer

See also

• Cancer
• Carcinogenesis

References

1. ^ Allen PJ, Bowne WB, Jaques DP, Brennan MF, Busam K, Coit DG (2005). "Merkel cell carcinoma: prognosis and treatment of patients from a single institution". J. Clin. Oncol. 23 (10): 2300–9. doi:10.1200/JCO.2005.02.329. PMID 15800320. 
2. ^ "New virus linked to rare but lethal skin cancer". The Age. http://news.theage.com.au/new-virus-linked-to-rare-but-lethal-skin-cancer/20080119-1muc.html. Retrieved 2008-02-26. 
3. ^ Hodgson NC (2005). "Merkel cell carcinoma: changing incidence trends". J Surg Oncol 89 (1): 1–4. doi:10.1002/jso.20167. PMID 15611998. 
4. ^ Gupta SG, Wang LC, Peñas PF, Gellenthin M, Lee SJ, Nghiem P (2006). "Sentinel lymph node biopsy for evaluation and treatment of patients with Merkel cell carcinoma: The Dana-Farber experience and meta-analysis of the literature". Arch Dermatol 142 (6): 685–90. doi:10.1001/archderm.142.6.685. PMID 16785370. http://archderm.ama-assn.org/cgi/content/full/142/6/685. 

External links

• Merkel Cell Cancer Discussion Group
• "Merkel cell carcinoma--Information for Patients & Their Physiciansis". Seattle Cancer Care Alliance. 2008-03-25. http://www.merkelcell.org/. Retrieved 2008-04-13. 
• National Cancer Institute (01/02/2007). "Merkel Cell Carcinoma: Questions and Answers". National Institutes of Health (US). http://www.cancer.gov/cancertopics/factsheet/Sites-Types/merkel-cell. Retrieved 2008-04-13. 

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