Yes. There are observational (clinical database) studies and therapeutic research trials ongoing. Click here to learn more about participating in MCC research.
The answer to this question is not known with certainty, but multiple lines of evidence suggest that Merkel cell carcinoma does NOT derive directly from normal Merkel cells. This is in part because it has proven impossible to get a normal Merkel cell to divide and grow. It is more likely that the precursor of a normal Merkel cell (a stem cell in the epidermis) gives rise to both the normal Merkel cell and separately, to Merkel cell carcinoma. There are several studies that have determined that normal Merkel cells are derived from epidermal precursor cells.
An active support group exists for MCC. Learn more about getting support and joining support groups with other MCC patients and their friends and family members.
Probably not. There are no data suggesting that MCC runs in families. In fact, there are no reported cases of MCC occurring in multiple members of one family. However, through our cohort of over 1000 patients and others who have contacted us directly, we are now aware of four separate families in which two closely related family members had MCC. We do not think this supports the notion that MCC risk particularly runs in families.
Recent genetic studies have shown that Merkel cell carcinomas are caused either by mutations induced by sunlight or by the Merkel cell polyomavirus. Risk factors strongly associated with the development of MCC include fair skin, a history of extensive sun exposure, chronic immune suppression (kidney or heart transplantation or HIV), and over age 50.
MCC usually develops on sun-exposed skin as a firm, painless, flesh-colored to red-violet bump. The initial small bump tends to grow rapidly over weeks to months. Some images can be seen on our Clinical Photos page.
The lymphatic system is a system of vessels and lymph nodes throughout the body. It serves an important function in the immune system. Lymph nodes act as filters to trap cancer cells as they travel through the lymphatic vessels. The lymph nodes that filter the legs are in the inguinal region between the thigh and the abdomen. The lymph nodes that filter the arms are in the armpit (axilla). Those that drain the skin of the face can be under the chin (submandibular), along the neck (cervical), or around the ears (pre/post-auricular).
Merkel cells are found in the epidermis (outer layer of the skin). Although the exact function of Merkel cells is unknown, they are thought to be touch receptors. They have both sensory and hormonal functions and are sometimes referred to as neuroendocrine cells. Learn more about Merkel cells.
The antibody titer is the standard measure of how much of a particular antibody is in the blood. The titer value increases as the amount of that antibody increases in the blood.
An antibody is a highly specific protein made by our bodies that can recognize and bind to an agent such as a bacteria or virus.
MCC, also referred to as neuroendocrine carcinoma of the skin, arises from uncontrolled growth of cells that share some characteristics with normal Merkel cells of the skin. It is a rare skin cancer with an incidence of about 2,000 cases per year in the US, and this number is continuing to increase. MCC will prove fatal in roughly 1/3 of patients and should receive prompt, but appropriately customized treatment.
Merkel cell carcinoma is rare, so it is common for many medical professionals to be unsure of where to start. When a diagnosis occurs, it is imperative that your medical team be knowledgeable, as they will need to execute the plan that MCC specialists will create. Our clinical team recommends that all healthcare providers follow the NCCN guidelines for MCC to bring them up to speed about MCC and how to care for patients.
MCC primarily occurs on highly sun-exposed skin such as the head/neck and arms, but it can occur anywhere on the body, including sun-protected areas such as the buttock. Learn more about the symptoms and appearance of Merkel cell carcinoma.
Individuals over the age of 65 are far more likely to develop MCC. Fair skin and a history of extensive sun exposure also increase the chances. MCC is associated with weakened immune function, such as in patients with HIV or organ transplants. However, over 90% of people who get MCC have no known immune suppression.
Yes. Ensuring that cancer patients have a good diet, sufficient exercise, and a realistic but optimistic outlook is likely to improve the efficacy of traditional cancer care as well as quality of life.
It has recently been realized that MCC patients with nodal disease who have no known primary lesion do better than node-positive patients who still have a primary lesion in place. These two categories of Stage III (nodal) disease are separated in the new system, resulting in more accurate prediction of recurrence. In the 8th Edition system, it is now necessary to note whether staging was ‘clinical’ or ‘pathologic’ (see table in 8th Edition system) for a summary.
There is no cut off time. In the past, people have used 5 years as the cut off but that is no longer applicable since treatments are much more effective now. The guidelines for coding malignancy state: “When a primary malignancy has been previously excised or eradicated from its site and there is no further treatment directed to that site and there is no evidence of any existing primary malignancy, a code from category 285.821: Personal history of malignant neoplasm, should be used to indicate the former site of the malignancy.” The intent of the history codes (in the cases of history of MCC you would use 285.821) is to indicate that the condition no longer exists and is not receiving any treatment, but that has the potential for recurrence, and therefore may require continued monitoring.”
If the recurrence happened after treatment had ended and the patient was in the history phase, then it would be coded using a Chapter 2-Neoplasms code for the new malignancy (even if it is recurring at the site of the previous malignancy) AND ALSO code 285.821 to show that there was a history.
Currently the index includes the sites of genital and buttock to code C4A.8: Merkel cell carcinoma of other sites. We also include “specified site not elsewhere classified” to this code (C4A.8) in case a site would be documented that is not specifically in the index.
A physical exam may reveal a new skin lesion, an enlarged lymph node or an enlarged liver that may signal the spread of MCC. A lesion of metastatic MCC may appear as a 1-3 cm, flesh-colored to red-purple bump that feels firm, is deeper compared to the primary lesion, and grows rapidly over a period of 2-4 weeks. The AMERK serology test can be an inexpensive, safe and sensitive approach to detect early recurrence. See the Symptoms and Appearance of MCC page for common sites of MCC metastasis. Blood tests, such as liver function tests (LFTs), may be used to detect the spread of MCC to internal organs, such as the liver. If a doctor is suspicious of distant metastases, he or she may use non-invasive imaging techniques, such as chest X-ray, CT (computed tomography) scans, and PET (positron emission tomography) scans.
You can increase your chance of survival by working with a team of doctors that is familiar with the unique management of MCC. In most cases, getting a sentinel lymph node biopsy is the best way to determine how advanced your cancer is. MCC is not the same as small cell lung cancer, and thus should usually not be treated with chemotherapy alone. Similarly, MCC is not the same as melanoma, and thus extra consideration should be taken before treating with surgery alone. Another important aspect of your treatment is to continue to eat a healthy diet and get regular exercise to help keep your immune system and overall health strong.
No. Participation in these ‘scientifically unproven’ approaches to cancer therapy should be strictly voluntary. Some patients are very keen to use these approaches and others have no interest. We never push our patients to engage in any specific alternative approach.
Your chance of beating MCC depends on how advanced the disease was when it was diagnosed, what treatment you receive and if your immune system is functioning properly. The “stage” of your cancer refers to whether the cancer is only in the skin, has spread to the lymph nodes or has spread elsewhere in the body. In general, about 1/3 of all MCC patients will succumb to this disease.
People with severe defects in “T lymphocytes” (key cells of the immune system) have a 10-30 times greater chance of developing MCC and twice the chance of losing the battle with MCC compared to people with a normal immune system. The conditions that cause such severe T lymphocyte defects include HIV (AIDS), taking immune suppressive drugs after solid organ transplantation, and certain immune cancers such as chronic lymphocytic leukemia. In contrast, suffering from more “colds” than average will not importantly affect your ability to fight MCC.
After your initial treatment, you will need to be followed closely by a physician to do regular skin and lymph node exams and take a thorough history. Visits should be approximately every 3 months for year 1 and then every 3-6 months for year 2, and then annually after that.
Even after treatment, some people’s oncoprotein antibody titers may never become fully negative. Patients may stabilize at a low positive oncoprotein antibody titer (<2000). Regardless, a significant decrease in oncoprotein antibody titers is expected after treatment.
Among 230 tests with falling or newly negative titers, the patient had no evidence of disease recurrence in 226 instances. In this setting, surveillance per routine guidelines (available via nccn.org) should be followed.
The serology test is NOT meant for diagnostic or screening purposes, since MCC can only be diagnosed through a biopsy.
No, a patient can give blood at any time of day and does not need to fast.
If a patient is positive for the oncoprotein antibody, then he has the Merkel virus in his cancer. If a patient is negative for the oncoprotein antibody, it is not clear whether or not he has the virus in his cancer.
A patient’s medical team must fill out the order form and ship the sample to UW Lab Medicine in Seattle.
The certifications and licenses can be found here: UW Department of Laboratory Medicine Licenses and Accreditations UW Department of Laboratory Medicine CLIA License UW Department of Laboratory Medicine CAP Certificate
Physicians/staff based outside of the University of Washington (UW) system should contact the local laboratory where patients will have their blood sample collected (prior to shipment of serum to the UW Department of Laboratory Medicine) to initiate the process. The local laboratory “send out test coordinator” should contact the UW Reference Laboratory Services Call Center at 206-685-6066. UW Reference Laboratory Services will set up an account for the ordering physician/clinic, collect the required billing and reporting information, and provide requirements for sample collection, processing and shipping from the local laboratory.
The rate of decrease in antibody titers varies from patient to patient, but typically will fall by more than half in the first year.
For patients who make oncoprotein antibodies, we typically recommend an interval of 3 months between two tests. Depending on the stage of the disease and other risk factors, after 3 to 5 years patients and their medical teams may choose to run the test less often or discontinue it.
The dedicated research efforts of the Moore-Chang Lab, Galloway Lab, Nghiem Lab and UW Clinical Immunology Lab were integral to this research.
Ongoing analysis of our results suggests that survival may be improved among patients who make oncoprotein antibodies. Whether or not patients make these antibodies does not currently affect how we treat MCC.
If a patient does not make oncoprotein antibodies when he has the disease, then the serology test won’t be helpful for monitoring. However, the patient should continue regular clinical visits and imaging studies as recommended by his medical team.
Among 23 tests with increasing titers, there was evidence of disease recurrence in 14 instances.
Yes. Once this one-time administrative process is complete, patient samples can be collected for the testing process (name of test is ‘AMERK’).
A higher titer of oncoprotein antibody is not directly associated with any change in the chances of beating the cancer. One cannot compare the values across patients because the antibody titers are only meaningful if tracked over time for an individual patient. Changes in antibody titers are more important than the specific titer value itself.
After determining whether a patient makes these antibodies, we do not use this test if MCC remains clinically detectable. In such cases, it is preferable to track known disease using radiologic imaging or physical exam as appropriate.
The testing procedure involves a small-volume blood draw. No major risks or side effects of the testing procedure have been identified.
Patients with a borderline result (a titer of 75-150) for the oncoprotein antibody test at a time when MCC was present may or may not make antibodies to the oncoprotein. The effectiveness of monitoring through the serology test is unclear in such patients.
There are 2 possible explanations: The test result is inaccurate There may be a very small MCC recurrence that can not be seen on the scan and that the patient’s immune system may or may not eliminate A follow-up serology test and imaging study may be indicated in a few months.
A positive capsid antibody result means a person has been exposed to the Merkel virus in the past. It does not have any bearing on whether the person has active MCC. Capsid antibodies cannot be used to track the disease.
Only 50% of newly diagnosed MCC patients make oncoprotein antibodies. A negative test for oncoprotein antibodies when a patient has the disease means that the patient does not make antibodies and therefore the serology test will not be a useful tool to monitor the disease. A positive test for oncoprotein antibodies (titer>150) means that the serology test can be used to track the disease, and we would expect antibody titers to decrease after the cancer is successfully treated.
This test detects antibodies to the capsid protein and the oncoprotein of the Merkel virus in the blood.
If a patient is receiving regular serology tests, an increase in oncoprotein antibody titers – with or without symptoms – is concerning for a recurrence. An increase in oncoprotein antibody titers should be discussed with the patient’s physician who may consider ordering an imaging study.
As of 2014, the charge for UW Lab Medicine to perform this test will be approximately $200. The facility that orders the test will also charge for the blood draw, isolating serum, shipping and tracking the sample, recording and reporting the results. The total cost will therefore vary significantly between facilities.
The Merkel virus was first discovered in 2008 (by Patrick Moore and Yuan Chang’s group) and is now known to play a role in >80% of Merkel cell carcinomas (MCCs). The virus is commonly found on people’s normal-appearing skin and typically causes no problems. Important components of this virus include: The capsid protein (VP1) is a structural protein on the outer layer of the virus. The oncoprotein (T-antigen) is a separate protein encoded by the virus.
The ‘sensitivity’ of a test reflects the ability of the test to find the disease when it is present. The sensitivity of the oncoprotein antibody test is 78%. The data used to calculate these numbers are below in the ‘2 by 2’ table among 253 samples. First Recurrence Evidence of Disease Recurrence Serology Test Results Positive Negative Increasing 14 4 Decreasing 4 226
In general, the ‘specificity’ of a test reflects how accurately the test identifies absence of disease among those who are without disease. The specificity of the oncoprotein antibody test is 98%.
In general, labs at larger hospitals are more accustomed to arranging ‘send out’ tests. The ordering facility must set up an account with the testing facility in order for ‘send out’ testing to be done, but after the first time, it is easier to order additional tests. Alternatively, having your local provider ‘order’ the test through their affiliated hospital or clinic lab may make the process easier for you.
See the UW Laboratory Test Catalog here.
This test is for patients with biopsy-proven MCC who want to monitor their disease status for recurrence.
The research was funded in part through grants from the National Institutes of Health (NIH), the American Cancer Society (ACS) and many generous donors.
This test is not useful for MCC patients who did not have oncoprotein antibodies at a time when they had evidence of MCC.
The results will be sent to the ordering physician’s office typically in less than one month.
Between 2008 – 2013, the costs of shipping & analyzing blood for Merkel virus antibodies was covered by patient donations and grants from the NIH. The research phase was successfully completed at the end of 2013 and we now know when the test is useful, when it is not, and how results can be interpreted. Since January 2014, the test has been performed as a ‘clinical’ test, like most other blood tests. Because the lab that draws your blood does not perform this test, the blood needs to be ‘sent out’ to a facility that does perform the test, such as the University of Washington Medical Center in Seattle.
As this is a new test for a rare disease, different insurance companies may or may not cover the cost of the test.
CT scans (or “CAT” scans), X-rays, MRI, bone scan and PET scans are different types of imaging to look inside the body. They are sometimes used to find cancer inside the body that is not evident from the outside. There is a lot of controversy about how to use such scans. They are particularly important if MCC has been found to have spread to the lymph nodes to evaluate if significant disease has also developed elsewhere. In general, scans are far less effective in detecting early spread than a sentinel lymph node biopsy. Learn more about testing for MCC.
Cancer cells from an MCC tumor can break off and go into the lymphatic system or the blood. These cells can then go elsewhere in the body where they can either be killed by the immune system or take residence in a new location and start growing as a metastasis (tumor in another part of the body).
In general, cancers are staged according to where the cancer is in the body: local (skin only), nodal (involves the lymph nodes), or metastatic (spread elsewhere in the body). The best survival is for local stages; the poorest is in metastatic stages with nodal disease somewhere in between. In the past, there were five different staging systems for MCC, and this created confusion. The AJCC 7th Edition Staging Manual, which is the first international “consensus” staging system, will be officially replaced by the 8th Edition at the start of 2017.
While an MCC on the skin can look quite unconcerning (like a cyst or folliculitis lesion), under the microscope, MCC can easily be identified as a cancer of the ‘small blue round cell’ category. When a lesion falls into that category, the pathologist almost always orders a set of tests as described above (CK20, TTF1, etc). In the vast majority of cases, the pattern of CK20 and other tests makes the diagnosis of MCC quite easy for the pathologist.
Because MCC has already spread to the adjacent lymph nodes that feel normal in nearly one third of cases at diagnosis, figuring out whether this has happened or not helps in properly “staging” a patient, and thus in more accurately predicting the chance the cancer will recur. If the nodes are involved, treating them with radiation or surgery markedly reduces the risk the cancer will come back in those nodes.
While there is agreement that radiation therapy lowers the risk of MCC recurrence, there is great controversy as to exactly which patients should receive this therapy. The side effects, cost, and inconvenience of radiation therapy can be significant. Patients with extremely low risk disease should not receive radiation, and patients with high risk disease should be offered this therapy. Determining which moderate-risk disease patients should receive radiation is very tricky and needs to be customized for each patient’s philosophy regarding recurrence risk versus side effects. Ideally, this discussion should take place with a multi-disciplinary team that is very familiar with the relevant literature and the risks and benefits of radiation therapy for MCC.
It is important to perform a sentinel lymph node biopsy at the time of (or prior to) a significant re-excision surgery. This is because extensive surgery at the site of the tumor disrupts the tiny lymphatic vessels that connect the tumor to the regional 1-2 lymph nodes where the cancer may have spread microscopically.
MCC can spread to other areas of the skin, the lymph nodes, or anywhere else in the body including the liver, bone, lung, and brain.
Typically not. Mohs surgery is typically done in a dermatologist’s office. A sentinel lymph node biopsy is typically done in an operating room by a surgical oncologist, using general anesthesia. If a patient needs a node biopsy, it typically needs to be done in advance of Mohs surgery, by a different physician.
A sentinel lymph node biopsy (SLNB) is a procedure in which a radioactive dye is injected near the primary tumor site, and the one to three nearby lymph nodes that “light up” (take up the dye) are removed by the surgeon and sent for pathologic examination (microscopic evaluation by a pathologist). This SLNB procedure is usually performed at the time of surgery and is much less accurate if a wide surgical excision has already been done. SLNB is important because MCC can spread by lymphatic vessels very early in the disease. At such a time, disease spread is not detectable by palpation (feeling the lymph nodes) or by scans but is readily detected by this test. For these reasons, SLNB is the best way to determine if MCC has spread elsewhere in the body, and it can help determine if the local lymph nodes require treatment.
In general, chemotherapy is reserved for late stages of MCC, when immune therapies are not an option. For disease that is not metastatic, good control can often be achieved with surgery and radiation alone.
A surgical excision is usually performed after a diagnostic biopsy as the first step of appropriate treatment for MCC. The goal of surgery is to remove any remaining cancer that can be seen either by the naked eye or under a microscope.
Immune checkpoint inhibitors are given through clinical trials, off-label, or compassionate use (where the pharmaceutical companies pay for the therapy).
In most cases, complete surgical excision of the tumor should be carried out immediately following a sentinel lymph node biopsy procedure. After a few weeks of healing, in many cases, radiation therapy to the primary tumor site and sometimes the draining lymph node area may be appropriate. If no cancer remains after surgery and radiation, we do not typically recommend adding adjuvant chemotherapy for a variety of reasons as outlined here. Learn more about MCC treatment options.
Your MCC case should be reviewed by a multidisciplinary team including surgical oncologists, radiation oncologists, medical oncologists, and dermatologists with significant experience in managing MCC to develop a plan that could then be carried out by your local physicians. It is important that you and your doctors realize that optimal management of MCC is different than that for small cell lung carcinoma and for melanoma. The most significant difference is the important role of radiation in managing many cases of MCC. Another important difference is that adjuvant chemotherapy has not been shown to improve survival in MCC. Learn more about treatment options for MCC.
Every clinical trial have a different set of requirements, but can limit enrollment based on age, tumor size, extent of disease, past treatments and immune status.
There are currently no immune checkpoint inhibitors that are FDA-approved for treating MCC. However, this will most likely change in 2017. Pembrolizumab was recently listed as a treatment option for patients with metastatic MCC on the NCCN guidelines. This drug is approved by the US FDA for treatment of other cancers and can be prescribed by oncologists outside of clinical trials. Avelumab has received orphan drug and breakthrough drug status for its use in MCC.
In some cases, especially if MCC has spread beyond the local-nodal area, we have successfully used a single, larger dose (8 Gy) of radiation to shrink and sometimes eliminate a given metastatic lesion. This approach has relatively few side effects and may work nicely together with systemic immune stimulation therapy. We described this approach in a 2015 report on 93 tumors treated in 26 patients.
This is an extremely tricky and controversial point. If radiation will be used, then surgical margins can be very small and narrow (just taking out the obvious portion of the tumor provides superb results when combined with adjuvant radiation). In contrast, if radiation is not planned, margins that are greater than 1 cm (ideally 2 cm) are associated with a lower risk of recurrence.
Typically, MCC clinical trials administer immune checkpoint inhibitors but also include chemotherapy, certain types of radiation, and combinations of therapies. Please explore the National Institutes of Health’s website to learn more about active MCC clinical trials, their eligibility, and location sites.
This is an extremely controversial area. Some studies, including ones by Bichakjian and Coit, suggest that MCCs can be treated with surgery alone, with very few patients experiencing relapse. Other studies suggest that radiation cuts the risk of local recurrence by 2-3 fold. A reasonable approach is that surgical excision alone is likely sufficient for certain low-risk tumors. For example, no radiation is usually needed if the tumor is relatively small (<2cm), the sentinel lymph node biopsy is negative, larger surgical excision margins are achieved (typically about 2cm), there is no lymphovascular invasion noted by the pathologist, if the pathologist cannot find any tumor cells at the margin, and if the patient is not immune suppressed. If these higher risk factors are present, it means there would likely be greater benefit of adding radiation therapy.
The authoritative source on Merkel cell carcinoma.
February 14, 2017