Diagnosis & Staging
Diagnosing Merkel cell carcinoma (MCC)
Merkel cell carcinoma (MCC) is diagnosed with a test called a skin biopsy. This means a doctor, often a dermatologist, takes a small sample of the tumor. They then send this sample to a lab so it can be looked at under a microscope, to check if the sample contains cancer.
All patients need biopsies to know if a bump is MCC or something else. This is the only way MCC can be diagnosed.
- This includes patients who previously had an MCC diagnosis
- Any new, concerning lesion should trigger a biopsy to see if the cancer has appeared or returned
Skin Biopsy
Dermatologists are the types of doctors who specialize in skin conditions and perform skin biopsies.
There are a few ways to do a biopsy:
- In a punch biopsy, the doctor takes a small core or circle of skin
- In a shave biopsy, the doctor scrapes off part of the top of the bump with a scalpel
After the skin sample is sent to the lab, another type of doctor, called a pathologist, will look at the skin sample under a microscope. They use special tests called immunohistochemistry stains to see if the cells are MCC or another type of cancer, such as small cell lung cancer, lymphoma, or melanoma. These tests help tell the different cancers apart from each other.
What happens after a positive biopsy
If a biopsy comes back positive for MCC, this means the skin bump (primary lesion) is confirmed to be cancerous.
It is at this point that you are diagnosed with MCC — but that is just the first step. Your doctor will do more tests to learn more about the cancer and if it has spread. These tests are important to help them find the stage of the cancer, plan your treatment, and understand the risk of your cancer returning in the future.
Next steps after diagnosis
Take a look at some of the first steps that you will take after you are diagnosed, before you start treatment.
Find and MCC specialist first
It is crucial for newly diagnosed patients to consult an MCC specialist as soon as possible. Doctors who are experts in this rare cancer can give you the best recommendations for testing and treatment, and help you plan next steps.
Staging
Finding out how big the tumor is and whether the cancer has spread
MCPyV test
Testing your biopsy sample for the virus that causes most MCC.
AMERK & ctDNA
Two blood draws that build a baseline for monitoring you later.
Staging
The first thing your doctors will want to do is find out the stage of the cancer. This is a routine step for all types of cancer. Finding the stage is like getting a weather report for your cancer. It tells doctors what is happening right now and helps them plan what to do next.
The stage of the cancer is determined by the size of the tumor and if the cancer has spread to the lymph nodes or other parts of your body. Doctors determine the stage of cancer by performing physical exams and tests, including:
- Measurements to see how big the tumor is
- Sentinel lymph node biopsies to see if the cancer has spread to nearby nodes
- Imaging scans to see if the cancer has spread to other parts of the body
MCPyV pathology test
Newly diagnosed patients should have their skin biopsy sample tested for the Merkel polyomavirus (MCPyV), a virus that commonly causes MCC. Identifying if a tumor was caused by the virus can give doctors information about how you should be monitored after treatment.
This is something the pathologist will do on their own — you don't have to do anything extra for this test if you've already had a skin biopsy.
- The same tumor sample taken from the skin biopsy that was used to diagnose your MCC can also be used to see if you have the active virus in your tumor. This is called a "CM2B4 antibody test"
- Pathologists will look at the sample to see if it contains a specific piece of the virus called the "oncoprotein". The oncoprotein is the portion of the virus that is key for making tumors grow
- A positive test: Tumors are "virus-positive" if they contain this oncoprotein. About 80% of MCC tumors have the oncoprotein and are positive for MCPyV
- A negative test: MCC tumors that do not contain the virus ("virus-negative MCC tumors") have a greater chance of coming back in the future after treatment, so it can be helpful for patients to know if they are virus-positive or virus-negative
- The same tumor sample taken from the skin biopsy that was used to diagnose your MCC can also be used to see if you have the active virus in your tumor. This is called a "CM2B4 antibody test"
- Pathologists will look at the sample to see if it contains a specific piece of the virus called the "oncoprotein". The oncoprotein is the portion of the virus that is key for making tumors grow
- A positive test: Tumors are "virus-positive" if they contain this oncoprotein. About 80% of MCC tumors have the oncoprotein and are positive for MCPyV
- A negative test: MCC tumors that do not contain the virus ("virus-negative MCC tumors") have a greater chance of coming back in the future after treatment, so it can be helpful for patients to know if they are virus-positive or virus-negative
Blood tests
Shortly after diagnosis, patients should have their blood drawn for two specific tests that are important to help doctors plan their care over time.
- MCPyV serology blood test looks at whether your body makes antibodies to the virus described above
- Circulating tumor DNA (ctDNA) test
These tests should ideally be done soon after diagnosis. The MCPyV serology test is less reliable if not done within a few months of diagnosis, and the ctDNA test can take time to build.
MCPyV serology testing (AMERK test)
Newly diagnosed patients should receive an MCPyV serology blood test within 2-3 months of diagnosis. The name of the test is the “AMERK” test, but this type of test can be called many things, such as a serology test, oncoprotein antibody test, or Merkel cell virus (MCPyV) antibody test.
This test requires a simple blood draw that can be done at any location and sent to the University of Washington in Seattle for analysis. See instructions below for how to order the test, and find additional information at the University of Washington’s AMERK testing page.
Patients who receive a positive MCPyV serology test after diagnosis can use this test in the future to monitor for cancer recurrence—learn more about monitoring for recurrence with the MCPyV serology test.
Please see the FAQ section on Serology testing for more information and explanations about the virus, antibodies, test, and interpretation of results.
he test looks for special antibodies that appear in the blood of some people in reaction to the oncoprotein portion of the virus.
A negative test
You do not make these oncoprotein antibodies. Your lack of antibodies puts you at a higher risk for having your cancer come back in the future. This is important to know so you can be monitored more closely and have more frequent imaging scans and/or circulating tumor DNA (ctDNA) tests.
A positive test
Your body does make these antibodies. Having antibodies means you can continue to use this blood test after treatment to check for signs that the cancer has come back. This is because antibody levels (called titers) normally drop by 90% in the first year after treatment, and if they start to rise again, it's concerning for recurrence. This gives your doctors a pattern to watch for. Repeating antibody tests in the years following treatment can alert you if your levels rise.
Only people whose bodies make antibodies in the first place can use this approach; people will not develop antibodies later if they did not have them earlier.
f you and your doctor determine that this test is appropriate, the doctor will order the test.
- How to order: A patient's medical team must fill out the order form and ship the sample to UW Lab Medicine in Seattle. The results will be sent to the ordering physician's office typically in less than one month.
- What to expect: The testing procedure involves a small-volume blood draw. No major risks or side effects of the testing procedure have been identified.
- Where to go: In general, labs at larger hospitals are more accustomed to drawing and processing blood.
- Expected costs: As of 2019, the charge for UW Lab Medicine to perform this test will be approximately $600 the first time the test is performed. Subsequent tests will cost approximately $300. The facility that orders the test will also charge for the blood draw, isolating serum, shipping and tracking the sample, and recording and reporting the results. The total cost will therefore vary significantly between facilities. As this test is for a rare disease, different insurance companies may or may not cover the cost of the test.
- Additional information: Find technical details regarding sample collection and handling in the UW Laboratory Test Catalog. The University of Washington CLIA and CAP accreditations relating to the serology test can be found at UW Department of Laboratory Medicine Licenses and Accreditations.
Please review the test requirements at testguide.labmed.uw.edu/public/view/AMERK
Ordering the test: Please complete the AMERK Requisition form in its entirety, including the address to send results to the ordering provider. Please include the clearly written name and NPI number of the ordering physician; this information is required to complete testing. Please ensure there are two patient identifiers on the form. The most common forms of patient ID are name and date of birth.
Receiving results: Test results will be received by the ordering physician between 2–3 weeks from the testing date. The patient should receive results through the ordering physician's care team. Contact information for the ordering physician should be added under "send report to" on the AMERK Requisition form. Please enter contact information for the ordering physician's department that handles results. All information must be clearly legible.
Questions: Contact the Client Support Services at 1-800-713-5198.
Download the form that will allow any medical facility to order the Merkel virus serology test.
AMERK Introductory video
We created a short video that explains how the Merkel virus serology test (called AMERK) works and how it helps doctors monitor MCC patients. Please also see the FAQ section on serology testing for more information and explanations about the virus, antibodies, test, and interpretation of results.
Circulating tumor DNA (ctDNA) testing
The ctDNA blood test is a simple blood draw that should be done during your initial workup after you are diagnosed with MCC.
This test looks for very small (microscopic) pieces of cancer DNA that have been “shed” from the tumor and that may be circulating in your blood stream. These pieces are harmless, and having them in your blood does not mean the cancer is spreading through your blood. However, having these pieces in your blood is a sign that MCC is present somewhere in your body—which is expected when you are diagnosed with MCC.
The ctDNA test is actually fully built and customized for you, based on your exact tumor markers. This can take some time to build upfront, which is why it’s good to have it done soon after diagnosis.
Later, once you have completed all of your treatments, doctors can use your personalized ctDNA test to check for any remaining or new signs of cancer in your body. This test can help find or predict any cancer that has come back, even before scans can see the cancer.
Patients can use ctDNA testing in the future to monitor for cancer recurrence—learn more about monitoring for recurrence with the ctDNA test.
Your first ctDNA test is simple for you, but quite complicated for the lab who receives your bloodwork. That's because they will actually be designing a personalized test for you. They do this by sequencing the DNA and blood and comparing them, to create a test that is customized to your specific tumor.
You may have to wait 4–5 weeks for the result when you take your first ctDNA test, because it takes time to create this personalized test for you. But once it's created, it can be used for all your tests in the future. Results from your future tests will come back in 1–3 weeks.
Seeing if MCC has spread
There are a few different types of tests that look to see if Merkel cell carcinoma (MCC) has spread from its original place on the skin to other places in the body. Doctors need to know where cancer is in your body in order to determine the stage of the cancer and create the best treatment plan for you.
- Cancer that is only in the skin is called local disease. If it has spread to local lymph nodes, it is nodal disease. Cancer that has spread the other places is called distant or metastatic disease
The most important test for newly diagnosed patients—whether this is their first diagnosis or a confirmed return of their cancer—is one called a sentinel lymph node biopsy. This test checks for whether MCC has spread to nearby lymph nodes, which is the first signal that disease has started to spread.
If the sentinel lymph node biopsy is positive, doctors will do additional tests to see if the cancer has gone to any distant organs. These include blood tests (such as liver function tests) and non-invasive imaging scans (such as chest X-rays, CT scans, and PET scans).
Sentinel lymph node biopsy (SLNB)
The single most important test for newly diagnosed patients. It checks whether MCC has reached the first lymph node it would travel to — often before any scan or physical exam could detect it.
Doctors use a special test called a sentinel lymph node biopsy (SLNB) to see if MCC has spread to nearby lymph nodes in the body. MCC can travel from the skin to the lymph nodes through tiny tubes called lymphatic vessels. This can happen very early in the disease, before physical exams and scans show any signs of spread, so sentinel lymph node biopsies are important to help catch the spread before it gets too far.
Lymph nodes are small, bean-shaped organs that help fight infection and act as filters that trap cancer cells. The "sentinel lymph node" is the lymph node that cancer spreads to first. You can think of it as the "priority" or "first stop" lymph node. In MCC, this is the lymph node closest to your cancerous skin lesion.
Why do a sentinel lymph node biopsy?
When cancer spreads to a lymph node, it can make the lymph node grow and get bigger. Sometimes, a lymph node with cancer will get noticeably larger so you can feel it, but sometimes it doesn't feel any different. If your sentinel node can't be felt on a physical exam, doctors need to remove it and test it to see if cancer is there. They do this with a sentinel lymph node biopsy, using dye to "light up" the sentinel node so that it is easier to find.
Patients diagnosed with an MCC on the skin should typically get a sentinel lymph node biopsy if their lymph nodes feel normal to the touch. If a patient has a lymph node that is already feeling abnormal or bigger, they should do a different type of ultrasound-guided biopsy, instead.
The sentinel node is difficult to find when it is normal size, so doctors use a blue dye and/or a safe radioactive liquid to help them find it. They inject this dye or liquid near where the cancer is on the skin. The dye and liquid travel the same path that cancer cells would take to the lymph node. After a few minutes, this shows doctors how to get to the sentinel lymph node.
Doctors use a special tool to find and remove the sentinel lymph node. Then, they look at it under a microscope to see if it has MCC cells. If MCC is not found in the sentinel node, the chance that the cancer has spread is much lower.
This test is safe, gives important information, and helps doctors know exactly which lymph node to check — even if the cancer is in a tricky spot, like a person's trunk. This procedure is typically done in an operating room by a surgical oncologist, using general anesthesia.
It is important to perform a sentinel lymph node biopsy at the time of (or prior to) the 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. Sentinel lymph node biopsies are usually performed at the time of surgery and are much less accurate if a wide surgical excision has already been done.
If you are scheduled for a Mohs surgery, the SLNB test should be done before your surgery by a different physician.
The sentinel lymph node is the first lymph node that connects with the part of the body where the cancer arose. A lymph node that contains MCC may feel enlarged (macrometastases) or may not feel enlarged (micrometastases).
Patients should be considered for sentinel node biopsy even if their primary MCC lesion is very small — even a very small lesion (under 0.5 cm) has at least a 15% chance of having already spread to nearby lymph nodes at the time of diagnosis.
One third of patients whose lymph nodes feel normal in fact already have microscopic spread of MCC to the sentinel lymph node(s) near where the MCC arose. Treatment by radiation or surgery of the area where those involved node(s) were markedly lowers the risk of MCC recurring within that area.
Imaging (scans)
Imaging is when doctors use scans to see what's happening inside your body.
For MCC, imaging scans are used to find cancer inside the body that cannot be seen or felt from the outside.
Imaging is common in medical practices for lots of different problems. Scans are particularly important if MCC has been found to have spread to the lymph nodes (from the sentinel lymph node biopsy), in order to check if disease has also developed in other parts of the body. In general, scans are far less effective in detecting early spread than a sentinel lymph node biopsy, so the SLNB test is usually done first.
Types of imaging include CT (computed tomography) scans, X-rays, MRI (magnetic resonance imaging), PET (positron emission tomography) scans, and bone scans.
CT scans and PET-CT scans take 3-dimensional pictures of areas inside of the body, from different angles. The pictures are created by a computer linked to an x-ray machine. You may also see these scans called computerized axial tomography scans, computed tomography scans, or computerized tomography.
Sometimes, a patient may be given contrast dye before the exam, which helps problem areas appear brighter in the images. This is given either as an injection (with a needle into the vein) or by mouth (often in a drink). Think of contrast dye like a camera flash in a dark room, making tumors and lesions easier to see on the final picture.
Stages of disease
The stage of Merkel cell carcinoma at diagnosis is very important for choosing the right treatment and understanding the chances of the cancer spreading or coming back.
Doctors find the stage by doing physical exams and tests that measure the size of the main tumor and check if the cancer is in the lymph nodes or any other parts of the body.
How doctors stage MCC
Stages describe the extent of cancer within the body, especially whether the disease has spread (metastasized) from the primary site to other parts of the body.
Doctors use a special system to decide the stage of MCC. Since 2018, they use the 8th Edition of the AJCC Staging Manual. This system was created by looking at information from over 5,000 patients and is now used around the world.
| Stage | What it means | How doctors confirm it |
|---|---|---|
| Stage I | Cancer is only in the skin. The main tumor is 2 cm or smaller. | Measuring the tumor, plus a sentinel lymph node biopsy showing no spread |
| Stage II | Cancer is only in the skin. The main tumor is larger than 2 cm, or has grown into deeper tissue such as muscle or bone. | Measuring the tumor, plus a sentinel lymph node biopsy showing no spread |
| Stage III | Cancer has spread to nearby lymph nodes, or to skin between the tumor and those nodes. | Physical exam, imaging, and/or a sentinel lymph node biopsy showing cancer in the nodes |
| Stage IV | Cancer has spread to other parts of the body farther from the original area, such as the liver, lung, bone, or brain. | Imaging scans, and a biopsy of the suspected distant site |