All About Merkel Cell Carcinoma

Author: OncoLink Team
Last Reviewed: June 30, 2020

What is a Merkel cell?

The neuroendocrine system is made up of cells that are spread throughout several organ systems, including the skin, lungs, and digestive system. They are called neuroendocrine cells because they have characteristics of both nerve and endocrine cells. Nerve cells use electrical impulses to transmit signals. Endocrine cells make up glands, such as the thyroid and pancreas. These glands secrete hormones (such as thyroid hormone and insulin), that can be used to communicate with other organs. Neuroendocrine tumors start in the cells of these hormone-producing organs. Merkel cell carcinoma is a type of neuroendocrine tumor.

Merkel cells are located near the top layer of the skin (the epidermis). Merkel cells are very close to nerve endings that process the sensation of touch, thus they are often referred to as “touch cells.” Because Merkel cells also produce hormones, they are neuroendocrine cells.  

What is Merkel cell carcinoma?

Merkel cell carcinoma (MCC) is a rare type of neuroendocrine tumor that is found in the skin. It is also called trabecular cancer. Like other cancers, MCC happens when collections of cells (in this case Merkel cells) grow abnormally or without control and form a tumor. 

What causes Merkel cell carcinoma and am I at risk?

There are about 2,000 cases of Merkel Cell carcinoma diagnosed each year in the United States. The incidence of MCC is increasing due to better tests to detect MCC. 

Like other skin cancers, sun exposure is a major risk factor for MCC. Individuals who have received PUVA (psoralen and UVA light) treatment for certain skin conditions including eczema, psoriasis, and CTCL may also be at an increased risk for developing MCC. MCC occurs more frequently in men, Caucasians, and those over the age of 50. 

MCC is also associated with a virus called Merkel Cell Polyomavirus (MVPyV). About 80% of patients with MCC in the US carry MVPyV. 

Individuals who are immunosuppressed (recipients of organ transplants, those with CLL or HIV) may also be at a higher risk for developing MCC.

How can I prevent Merkel cell carcinoma?

The best way to prevent MCC is to protect the skin from exposure to ultraviolet light, which includes natural UV light from the sun and artificial UV light from tanning devices.

Some ways to protect your skin from UV light include:

  • Do not use tanning salons or expose yourself to other artificial sources of UV light.
  • Avoid sun exposure between 10 am and 4 pm.
  • Seek the shade when outdoors.
  • Wear protective clothing, including long-sleeved shirts, pants, a hat, and sunglasses. You may choose to wear clothing that has built-in sun protection factor (SPF).
  • Use sunscreen with a sun protection factor (SPF) of 15 or greater every day, even in the winter! Consistent use of sunscreen has even shown the ability to reduce further skin damage in people with a history of extensive sun exposure. 
  • Examine your skin regularly and report any changes including rapidly growing, non-painful red/pink/purple lumps that occur on skin that has been exposed to the sun.

What screening tests are used for Merkel cell carcinoma?

The best screening test is a skin examination. Your healthcare provider should examine your skin during routine physicals, but you should also examine your skin routinely at home. Because you see your skin every day, you are most likely to notice any changes early on.  

What are the signs of Merkel cell carcinoma?

Merkel cell tumors can appear as non-painful, firm, red, pink, or purple lumps on areas of the skin that have been exposed to the sun. They can grow quickly and may erupt to form ulcers or sores on the skin. MCC can spread rapidly to surrounding lymph nodes.

How is Merkel cell carcinoma diagnosed?

The best way to diagnose MCC is with a skin biopsy. A skin biopsy is the removal of skin which is then looked at under a microscope by a pathologist. If the biopsy is positive for MCC, further laboratory testing will be performed. This can include testing for the presence of MVPyV and this virus’ associated antibodies. Individuals who do not have the virus may be more likely to have tumors that will progress or reoccur and require more frequent ongoing monitoring. Other tests used in the work-up of MCC include lymph node biopsy (sentinel lymph node biopsy, fine needle aspiration or surgical excision), MRI, CT, or PET-CT scan which can help determine if the cancer has spread. 

How is Merkel cell carcinoma staged?

MCC is staged to guide treatment. Healthcare providers use the TNM system (also called tumor - node - metastasis system). This system describes the size and how invasive the tumor is (T), which, if any, lymph nodes are involved (N), and if it has spread to other more distant areas of the body (M). The TNM then corresponds to a stage or I trough IV. Stage I is the earliest and most limited stage, with stage IV being a more advanced stage. Information used to stage MCC comes from the clinical workup (CT scans) and pathology (information learned from the biopsy). 

The staging system is outlined at the end of this article. Though complicated, the staging system helps healthcare providers define the extent of the cancer, and in turn, make treatment decisions for a patient's cancer. 

How is Merkel cell carcinoma treated?

Many providers have never seen or cared for a patient with MCC. It is important to seek out a healthcare team familiar with MCC. Your care team may include a dermatologist, surgeon, medical oncologist, and/or radiation oncologist.

Surgery

Surgery is often the first line of treatment for MCC. The goal of surgery to remove the entire MCC lesion while preserving as much surrounding healthy tissue as possible. This may be done through excision of the tumor, MOHS surgery or complete circumferential peripheral and deep margin assessment (CCPDMA). 

Radiation

After surgical removal, radiation may be used to further treat the MCC. Radiation therapy uses high energy x-rays to kill cancer cells. Radiation therapy after surgery has been shown to decrease the risk of recurrence of MCC. Radiation is typically delivered daily for several weeks. 

Chemotherapy

Even when tumors are removed by surgery, microscopic cancer cells may be left behind and can spread to distant sites in the body. Chemotherapy is medication that can go throughout the entire body to kill cancer cells. Chemotherapy is used in MCC patients when cancer has spread regionally (i.e. to lymph nodes) or distantly (to other organs).

Some of the medications used to treat MCC include cisplatinetoposidecarboplatintopotecancyclophosphamidedoxorubicinepirubicin and vincristine. These medications may be used alone or in combination. The medications you receive depends on if the tumor is recurrent or has spread. If the tumor is found to have the PD1 or PDL-1 biomarker on its cells, targeted therapies including avelumab, pembrolizumab and nivolumab, may be used. 

Clinical Trials

There are clinical research trials for most types of cancer, and every stage of the disease. Clinical trials are designed to determine the value of specific treatments. Trials are often designed to treat a certain stage of cancer, either as the first form of treatment offered or as an option for treatment after other treatments have failed to work. They can be used to evaluate medications or treatments to prevent cancer, detect it earlier, or help manage side effects. Clinical trials are extremely important in furthering our knowledge of the disease. It is through clinical trials that we know what we do today, and many exciting new therapies are currently being tested. Talk to your provider about participating in clinical trials in your area. You can also explore currently open clinical trials using the OncoLink Clinical Trials Matching Service.

Follow-up Care and Survivorship

Once an individual has been treated for MCC, they will need to be closely monitored for recurrence. Physical examination, including a lymph node exam, is recommended every 3-6 months for the first 3 years after treatment is completed and then every 6-12 months. Your healthcare provider may order imaging tests (CT/PET) as well. It is important for patients to be vigilant about skin examinations and to report any changes to their healthcare provider immediately.

Fear of recurrence, the financial impact of cancer treatment, employment issues, and coping strategies are common emotional and practical issues experienced by MCC survivors. Your healthcare team can identify resources for support and management of these practical and emotional challenges faced during and after cancer.

Cancer survivorship is a relatively new focus of oncology care. With almost 17  million cancer survivors in the U.S. alone, there is a need to help patients transition from active treatment to survivorship. What happens next, how do you get back to normal, what should you know and do to live healthy going forward? A survivorship care plan can be a first step in educating yourself about navigating life after cancer and helping you communicate knowledgeably with your healthcare providers. Create a survivorship care plan today on OncoLink.

Resources for More Information

Merkellcell.org

This website provides in-depth diagnosis and treatment information. Created by physicians and researchers who specialize in MCC.

https://www.merkelcell.org

Skincancer.net

Provides educational information about various types of skin cancer, including MCC.

https://skincancer.net

Neuroendocrine Tumor Research Foundation (NETRF)

Along with its focus on research, NETRF is committed to supporting patients, families, friends, and caregivers by providing them with information and educational resources.

https://netrf.org/

Neuroendrocrine Cancer Awareness Network (NCAN)

NCAN’s mission is to intensify awareness of neuroendocrine and carcinoid tumors through education, research funding, and a telephone helpline for patients and caregivers.

https://www.netcancerawareness.org

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Appendix: Complete Merkel Cell Carcinoma Staging

American Joint Committee on Cancer (AJCC), 8thed., 2017

Primary Tumor (T)

Description

TX

Primary tumor cannot be assessed (e.g. curetted)

T0

No evidence of primary tumor

T1s

In situ primary tumor

T1

Maximum clinical tumor diameter ≤2 cm

T2

Maximum clinical tumor diameter ≥ 2 but ≤5 cm

T3

Maximum clinical tumor diameter ≥ 5 cm

T4

Primary tumor invades fascia, muscle, cartilage, or bone

Regional Lymph Nodes- Clinical (N)

Description

NX

Regional lymph nodes cannot be clinically assessed (e.g. previously removed for another reason, or because of body habitus 

N0

No regional lymph node metastasis detected on clinical and/or radiologic examination

N1

Metastasis in regional lymph node(s)

N2

In-transit metastasis (discontinuous from primary tumor; located between primary tumor and draining regional nodal basin, or distal to the primary tumor) without lymph node metastasis

N3

In-transit metastasis (discontinuous from primary tumor; located between primary tumor and draining regional nodal basin, or distal to the primary tumor) with lymph node metastasis

 

Regional Lymph Nodes-Pathological (pN)

Description

pNX

Regional lymph nodes cannot be assessed (e.g. previously removed for another reason or not removed for pathological evaluation

pN0

No regional lymph node metastasis on pathological evaluation

pN1a(sn)

Clinically occult regional lymph node metastasis identified by sentinel lymph node biopsy

PN1a

Clinically occult regional lymph node metastasis following lymph node dissection

pN1b

Clinically and/or radiologically detected regional lymph node metastasis microscopically confirmed

pN2 

In-transit metastasis (discontinuous from primary tumor; located between primary tumor and draining regional nodal basin, or distal to the primary tumor) without lymph node metastasis

pN3

In-transit metastasis (discontinuous from primary tumor; located between primary tumor and draining regional nodal basin, or distal to the primary tumor) with lymph node metastasis

 

Distant Metastasis Clinical (M)

Description

M0

No distant metastasis detected on clinical and/or radiologic examination

M1

Distant metastasis detected on clinical and/or radiologic examination

M1a

Metastasis to distant skin, distant subcutaneous tissue, or distant lymph node(s)

M1b

Metastasis to the lung

M1c

Metastasis to all other visceral sites

 

Distant Metastasis Pathological (M)

Description

M0

No distant metastasis detected on clinical and/or radiologic examination

pM1

Distant metastasis microscopically confirmed

pM1a

Metastasis to distant skin, distant subcutaneous tissue, or distant lymph node(s), microscopically confirmed

pM1b

Metastasis to the lung, microscopically confirmed

pM1c

Metastasis to all other distant sites, microscopically confirmed

AJCC Prognostic Stage Groups

Clinical Stage (cTNM)

T

N

M

0

Tis

N0

M0

I

T1

N0

M0

IIA

T2-3

N0

M0

IIB

T4

N0

M0

III

T0-4

N103

M0

IV

T0-4

Any N

M1a-c

 

Pathological Stage (pTNM)

T

N

M

0

T1s

N0

pM0

I

T1

N0

pM0

IIA

T2-3

N0

pM0

IIB

T4

N0

pM0

IIIA

T1-4

T0

N1b

pM0

IIIB

T1-4

N1b-3

pM0

IV

T0-4

Any N

pM1a-c

References

NCCN Guidelines, Merkel Cell Carcinoma, June 25, 2020 retrieved from, https://www.nccn.org/professionals/physician_gls/pdf/mcc.pdf(registration required)

Amaral, T., Leiter, U., & Garbe, C. (2017). Merkel cell carcinoma: Epidemiology, pathogenesis, diagnosis and therapy. Reviews in Endocrine and Metabolic Disorders, 1-16.

Flohil, S. C., Lee, C. B., Beisenherz, J., Mureau, M. A. M., Overbeek, L. I. H., Nijsten, T., & Bos, R. R. (2017). Mohs micrographic surgery of rare cutaneous tumours. Journal of the European Academy of Dermatology and Venereology31(8), 1285-1288.

Galluzzi, L., & Kroemer, G. (2017). Novel immune checkpoint blocker to treat Merkel cell carcinoma. Oncoimmunology6(6), e1315496.

Mattavelli, I., Patuzzo, R., Torri, V., Gallino, G., Maurichi, A., Lamera, M., ... & Moglia, D. (2017). Prognostic factors in Merkel cell carcinoma patients undergoing sentinel node biopsy. European Journal of Surgical Oncology43(8), 1536-1541.

Moshiri, A. S., Doumani, R., Yelistratova, L., Blom, A., Lachance, K., Shinohara, M. M., ... & Asgari, M. M. (2017). Polyomavirus-negative merkel cell carcinoma: a more aggressive subtype based on analysis of 282 cases using multimodal tumor virus detection. Journal of Investigative Dermatology137(4), 819-827.

Paulson, K. G., Lewis, C. W., Redman, M. W., Simonson, W. T., Lisberg, A., Ritter, D., ... & Iyer, J. (2017). Viral oncoprotein antibodies as a marker for recurrence of Merkel cell carcinoma: a prospective validation study. Cancer123(8), 1464-1474.

Paulson, K. G., Park, S. Y., Vandeven, N. A., Lachance, K., Thomas, H., Chapuis, A. G., ... & Nghiem, P. (2017). Merkel Cell Carcinoma: Current United States Incidence and Projected Increases based on Changing Demographics. Journal of the American Academy of Dermatology.

Poulsen, M. (2018). Radiation Therapy Rather Than Surgery for Merkel Cell Carcinoma: The Advantages of Radiation Therapy. International Journal of Radiation Oncology* Biology* Physics100(1), 14-15.

Spurgeon, M. E., & Lambert, P. F. (2013). Merkel Cell Polyomavirus: A Newly Discovered Human Virus with Oncogenic Potential. Virology435(1), 118–130. http://doi.org/10.1016/j.virol.2012.09.029

Tsai, S., & Bordeaux, J. S. (2018). Merkel Cell Carcinoma. In A Practical Guide to Skin Cancer (pp. 143-153). Springer, Cham.

Winkler, J. K., Bender, C., Kratochwil, C., Enk, A., & Hassel, J. C. (2017). PD‐1 blockade: a therapeutic option for treatment of metastatic Merkel cell carcinoma. British Journal of Dermatology176(1), 216-219.

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