Merkel cell carcinoma. A review.

Sept 2012

Pink R, Ehrmann J, Molitor M, Tvrdy P, Michl P, Pazdera J, Hanuliak J.

Source

Department of Oral and Maxillofacial Surgery, University Hospital Olomouc, Czech Republic.

Abstract

BACKGROUND: Merkel cell carcinoma (MCC) is a rare potentially fatal skin tumour affecting older mainly white people and younger immunosuppressed individuals. While uncommon, the incidence is increasing relative to melanoma and with twice the lethality. The benign appearance of the tumour usually on exposed skin parts, contrasting with its extensive microscopic invasion, can delay timely diagnosis. Recurrent MCC is currently attributed to the recently discovered Merkel cellpolyomavirus This brief review of MCC covers the history, epidemiology,etiology,clinical and histological features, treatment and prognosis. 

METHODS: Literature search using PubMed and search words Merkel cell carcinoma (MCC), etiology, treatment for the years 1972 to 2010. 

Results and conclusion. Merkel cell carcinoma is a rare malignancy with uncertain prognosis. Due to the uncommon occurrence and dearth of randomized studies, there is no agreement on optimal treatment. The tumor has only recently been included in the international classification of tumors (NCCN). The treatment approaches found to be best are radical surgery of primary tumor, drainage of lymph node extension and possibly adjuvant loco-regional radiotherapy. The basis of successful treatment however, remains prevention regular dermatological examination in immunosuppressed patients and early initiation of combination therapy, based on radical surgery supplemented by radiotherapy and palliative chemotherapy in the last resort.

Biomedical Papers

Quantitation of human seroresponsiveness to Merkel cell polyomavirus.

Quantitation of human seroresponsiveness to Merkel cell polyomavirus.
PLoS Pathog. 2009 Sep

Pastrana DV, Tolstov YL, Becker JC, Moore PS, Chang Y, Buck CB.
Laboratory of Cellular Oncology, National Cancer Institute, Bethesda, Maryland, USA.

Merkel cell carcinoma (MCC) is a relatively uncommon but highly lethal form of skin cancer. A majority of MCC tumors carry DNA sequences derived from a newly identified virus called Merkel cell polyomavirus (MCV or MCPyV), a candidate etiologic agent underlying the development of MCC. To further investigate the role of MCV infection in the development of MCC, we developed a reporter vector-based neutralization assay to quantitate MCV-specific serum antibody responses in human subjects. Our results showed that 21 MCC patients whose tumors harbored MCV DNA all displayed vigorous MCV-specific antibody responses. Although 88% (42/48) of adult subjects without MCC were MCV seropositive, the geometric mean titer of the control group was 59-fold lower than the MCC patient group (p less then 0.0001). protein, Only 4% (2/48) of control subjects displayed neutralizing titers greater than the mean titer of the MCV-positive MCC patient population. MCC tumors were found not to express detectable amounts of MCV VP1 capsid protein, suggesting that the strong humoral responses observed in MCC patients were primed by an unusually immunogenic MCV infection, and not by viral antigen expressed by the MCC tumor itself. The occurrence of highly immunogenic MCV infection in MCC patients is unlikely to reflect a failure to control polyomavirus infections in general, as seroreactivity to BK polyomavirus was similar among MCC patients and control subjects. The results support the concept that MCV infection is a causative factor in the development of most cases of MCC. Although MCC tumorigenesis can evidently proceed in the face of effective MCV-specific antibody responses, a small pilot animal immunization study revealed that a candidate vaccine based on MCV virus-like particles (VLPs) elicits antibody responses that robustly neutralize MCV reporter vectors in vitro. This suggests that a VLP-based vaccine could be effective for preventing the initial establishment of MCV infection.

PubMed

Treatment Option Overview by Stage for Merkel Cell Carcinoma

Treatment Option Overview by Stage for Merkel Cell Carcinoma

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How Merkel cell carcinoma is treated

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There are treatments for all patients with Merkel cell carcinoma. Three kinds of treatment are used:

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surgery (taking out the cancer)

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radiation therapy (using high-dose x-rays or other high-energy rays to kill cancer cells)

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chemotherapy (using drugs to kill cancer cells)

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There are several different types of surgery that may be used to remove the tumor. These include:

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Wide surgical excision takes out the cancer and some of the skin around the tumor.

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Cryosurgery freezes the tumor and then removes it.

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Micrographic surgery is a tissue-sparing technique that removes only the tumor.

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Radiation therapy uses high-energy x-rays to kill cancer cells and shrink tumors.

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Radiation may come from a machine outside the body (external radiation therapy) or from putting materials that produce radiation (radioisotopes) through thin plastic tubes in the area where the cancer cells are found (internal radiation therapy).

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Chemotherapy uses drugs to kill cancer cells. Chemotherapy may be taken by pill, or it may be put into the body by a needle in a vein or muscle. Chemotherapy is called a systemic treatment because the drugs enter the bloodstream, travel through the body, and can kill cancer cells throughout the body.

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If a doctor removes all the cancer that can be seen at the time of the operation, a patient may be given chemotherapy after surgery to kill any cancer cells that are left. Chemotherapy given after an operation to a person who has no cancer cells that can be found is called adjuvant chemotherapy.

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STAGE I MERKEL CELL CARCINOMA

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Treatment may be one of the following:

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1. Surgery alone.

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2. Surgery followed by radiation therapy to the tumor site and regional lymph nodes.

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STAGE II MERKEL CELL CARCINOMA

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Treatment may be one of the following:

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1. Surgery alone.

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2. Surgery followed by radiation therapy to the tumor site and regional lymph nodes.

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3. Surgery with or without radiation therapy followed by adjuvant chemotherapy.

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STAGE III MERKEL CELL CARCINOMA

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Treatment will probably be chemotherapy.

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RECURRENT MERKEL CELL CARCINOMA

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Treatment may be one of the following:

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1. Surgery alone.

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2. Surgery followed by radiation therapy to the tumor site and regional lymph nodes.

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3. Surgery with or without radiation therapy followed by adjuvant chemotherapy.

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Cancer Web UK

Stages of Merkel cell carcinoma

Stages of Merkel cell carcinoma
Stage Explanation

After Merkel cell carcinoma has been diagnosed (found), more tests will be done to find out if cancer cells have spread from the place the cancer started to other parts of the body. The process used to find out whether the cancer has spread to other parts of the body is called staging. It is important to know the stage of the disease to plan the best treatment. The following stages are used for Merkel cell carcinoma:

Stage I

The primary tumor has not spread to lymph nodes or other parts of the body. Lymph nodes are small, bean-shaped structures that are found throughout the body. They produce and store infection-fighting cells.

Stage II

The cancer has spread to nearby lymph nodes, but has not spread to other parts of the body.

Stage III

The cancer has spread beyond nearby lymph nodes and to other parts of the body.

Recurrent stage

Recurrent disease means that the cancer has recurred (come back) after it has been treated. It may come back in the same part of the body or in another part of the body.

Cancer Web UK

Merkel cell carcinoma within follicular cysts: report of two cases.

Merkel cell carcinoma within follicular cysts: report of two cases.
Requena L, Jaqueti G, Rütten A, Mentzel T, Kutzner H.

Department of Dermatology, Fundación Jiménez Díaz, Universidad Autónoma, Madrid, Spain.

Merkel cell carcinoma is a rare cutaneous neoplasm of unknown histogenesis. Several reports have described the association of Merkel cell carcinoma of the skin with other cutaneous neoplasms within the same lesion, and there are also reports describing three examples of Merkel cell carcinoma within follicular cysts. We describe two examples of Merkel cell carcinoma developed within epithelial cysts. Neoplastic cells of Merkel cell tumor expressed immunoreactivity for chromogranin, synaptophysin, neuron-specific enolase, CAM 5.2 and cytokeratin 20, the last two markers showing the characteristic paranuclear dot-like pattern. In contrast, the epithelial wall lining the cyst and surrounding Merkel cell tumor only expressed immunoreactivity for cytokeratin MNF116. The description of five cases of Merkel cell carcinoma within follicular cysts, including the two cases of this report, support some relationship between Merkel cell tumor and the hair follicle.

J Cutan Pathol. 2008 Dec

PMID: 18988316 [PubMed - in process]

Merkel Cell Carcinoma

Merkel Cell Carcinoma

MD Anderson Cancer Center

Merkel Cell Carcinoma

Merkel Cell Carcinoma (MCC) is a rare skin malignancy which was first described in 1972 by Cyril Toker. However, the name Merkel cell comes from the anatomist who discovered the normal Merkel cell in pig snouts - Friedreich Sigmund Merkel in 1875. Because of the tumor cell characteristics seen under the microscope, the name neuroendocrine carcinoma of the skin is used synonymously with Merkel cell carcinoma.

The true incidence of this cancer is not known, but 400 - 600 cases have been described in the literature. Merkel cell carcinoma is almost exclusively seen in Caucasian people, and most are more than 65 years old. Some of the literature reports that MCC affects men and women equally, but other studies have shown a male predominance. The etiology of this tumor is not clearly defined, but there has been association of MCC to sun exposure. Many of the patients have a history of other basal or squamous cell cancers of the skin, and approximately 10% of the patients will develop a second primary cancer.

Merkel cell carcinoma most commonly occurs in the skin of the head and neck (50%), followed by the extremities and the trunk. The head and neck, cheek, forehead, temple, nose, and upper neck are the most common sites. This tumor is innocuous in appearance - described as a painless, solitary, raised, pink nodule. Most tumors are less than 2 cm when initially discovered. Biopsy is the only way to diagnose MCC. However, the diagnosis is difficult for most pathologists, and requires both the use of the electron microscope and special staining of the cells to differentiate it from other small cell carcinomas.

Merkel cell carcinoma is a very aggressive cancer. Lymph node metastasis occurs early and often. Some studies report palpable lymph nodes at presentation in 45% of patients. However, distant metastasis is rare at presentation. Local and regional recurrence occurs frequently, and is felt to be related to the adequacy of the initial therapy. Distant metastasis occurs in approximately 25% of patients, regardless of therapy.

The current thoughts on treating Merkel cell cancer include both the primary lesion and the regional lymphatics. It is felt that the primary cancer should be surgically removed with negative margins. Studies have shown that surgical treatment alone has a higher rate of local and regional recurrence that those who receive surgical excision and radiation therapy. Thus, after the tumor is removed, 6 weeks of radiation to the surgical site and to the regional lymphatics is recommended. However, despite this aggressive therapy, approximately 40% still develop locoregional recurrence.

It is felt that regardless of therapy, 25 - 35% of patients may ultimately recur. It is felt that the development of locoregional recurrence is a predictor of multiple recurrence and distant metastasis. Thus, it is implied that early locoregional treatment will improve tumor control. However, it is not proven whether locoregional control will affect the rate of distant metastasis and ultimately affect survival.