Section Editor: Allison Osmond MD FRCPC
June 9, 2026
Merkel cell carcinoma is a rare type of skin cancer. It is a kind of neuroendocrine tumor, meaning it develops from neuroendocrine cells in the skin. Neuroendocrine cells are specialized cells that send signals by releasing chemical messengers in response to nerve activity. Merkel cell carcinoma tends to grow quickly and is more likely to spread than most other skin cancers, which is why finding and treating it early is important.
This article explains what the findings in your Merkel cell carcinoma pathology report mean, how the diagnosis is made, and how those findings guide the decisions you and your care team will make together. The outlook depends a great deal on whether the cancer has spread, and many people with disease that is found early are treated successfully.
What causes Merkel cell carcinoma?
Two main factors are linked to Merkel cell carcinoma, and many tumors involve one or the other:
- Ultraviolet (UV) radiation — Long-term sun exposure damages the DNA in skin cells. Tumors driven by UV damage tend to carry many genetic changes (mutations).
- Merkel cell polyomavirus (MCPyV) — In many cases, this common virus becomes built into the DNA of the tumor cells, where it produces proteins that switch off the normal controls on cell growth. Virus-positive tumors usually carry few other mutations.
Merkel cell carcinoma most often affects older adults, with a median age at diagnosis of about 75 years, and it is uncommon before age 50. It is more common in people with lighter skin and in regions with intense sun exposure. The risk is also higher in people with a weakened immune system, including those with HIV infection, organ transplant recipients, and people with certain blood cancers such as chronic lymphocytic leukemia.
What are the symptoms of Merkel cell carcinoma?
Merkel cell carcinoma usually appears as a quickly growing, firm, painless lump that is flesh-colored to reddish-purple. It is found most often on sun-exposed skin of the head and neck, arms, legs, or trunk. Because it grows fast, it may enlarge over weeks to months, and it can look at first like a harmless cyst or another, more common skin cancer. In some people, the cancer is first found in the lymph nodes without an obvious skin tumor, because the original skin spot shrank or disappeared on its own.
How is the diagnosis made?
The diagnosis is made after a biopsy or surgical specimen is examined under the microscope by a pathologist. Under the microscope, Merkel cell carcinoma usually appears as a dense collection of small, blue-staining tumor cells in the dermis (the layer of skin beneath the surface) and sometimes the fatty tissue below it. The cells are small to medium in size with very little cytoplasm (the material surrounding the center of the cell), so their nuclei (the part of the cell that holds the DNA) look crowded together. A characteristic feature is a fine, evenly speckled “salt-and-pepper” pattern within the nuclei, typical of neuroendocrine tumors, along with numerous mitotic figures (dividing cells), which reflect rapid growth.
Because these features can overlap with other cancers, the diagnosis is confirmed with immunohistochemistry, a test that uses special stains to detect specific proteins in the tumor cells. Merkel cell carcinoma typically shows neuroendocrine markers (such as INSM1, synaptophysin, chromogranin, and CD56) together with cytokeratins, the proteins found in epithelial cells. A very helpful finding is dot-like staining for CK20 and/or neurofilament next to the nucleus, a pattern that is highly characteristic of Merkel cell carcinoma. The tumor is usually negative for a marker called TTF-1, which helps the pathologist rule out small cell lung cancer that has spread to the skin. Once the diagnosis is confirmed, imaging is used to determine whether the cancer has spread and to assign the stage. Additional molecular and viral testing that carries prognostic information is described in the biomarker section below.
Histologic grade
Merkel cell carcinoma is not given the usual histologic grade (the well, moderately, or poorly differentiated scale used for many other cancers). It is considered a high-grade neuroendocrine carcinoma by definition, meaning the cells are fast-dividing and the tumor is expected to behave in a higher-risk way. For this reason, your report will usually not include a grade number, and this is expected for this diagnosis.
Depth of invasion
Merkel cell carcinoma starts in or just beneath the epidermis, the thin outer layer of the skin. Depth of invasion describes how far the tumor cells have grown down into the deeper layers of tissue. It is measured in millimeters from the surface of the skin to the deepest tumor cells, and some reports call this the tumor thickness. Tumors that grow more deeply are more likely to spread to lymph nodes or other parts of the body, and the measurement also helps determine the tumor stage.
Tumor extension
As Merkel cell carcinoma grows, it can extend beyond the skin into deeper structures such as muscle, cartilage, or bone. Pathologists call this tumor extension. Extension into deeper tissue is associated with a higher risk that the tumor will come back in the same area and a greater chance of spread, and it is used to help determine the tumor stage.
Tumor pattern of growth
The pattern of growth describes how the tumor cells are arranged under the microscope. Pathologists usually describe one of two patterns:
- Nodular — The tumor cells grow together in one or more compact, rounded clusters. This pattern is generally associated with a better outcome.
- Infiltrative — The tumor cells spread out as thin strands that weave through the surrounding tissue, sometimes resembling a spider’s web. This pattern is associated with a higher risk of spread and of returning after treatment.
Tumor-infiltrating lymphocytes
Lymphocytes are immune cells that help the body recognize and fight infection and cancer. In Merkel cell carcinoma, lymphocytes are often found in and around the tumor, which suggests the immune system is responding to it. Pathologists describe this response as brisk (many lymphocytes throughout and around the tumor, generally associated with a better outcome) or non-brisk (few lymphocytes, associated with a higher risk of spread).
Lymphovascular invasion
Lymphovascular invasion means that tumor cells are seen inside a blood vessel or a lymphatic channel. Blood vessels carry blood, while lymphatic channels carry a clear fluid called lymph. These vessels matter because tumor cells must first enter one of them before they can spread to lymph nodes or distant organs such as the lungs. Lymphovascular invasion is common in Merkel cell carcinoma, and when it is present the risk of spread is higher. Your report will state whether it was seen.
Surgical margins
A margin is the rim of normal-looking tissue removed around the tumor during surgery. For Merkel cell carcinoma, the pathologist examines both the peripheral margin (the skin around the tumor) and the deep margin (the tissue beneath it).
- Negative margin — No tumor cells are seen at the cut edge, which suggests the tumor was completely removed.
- Close margin — Tumor cells are near the cut edge but do not reach it. Depending on the distance, your doctor may discuss further surgery or radiation.
- Positive margin — Tumor cells are present at the cut edge, which means some tumor may remain. A positive margin is associated with a higher risk that the tumor will return at the same site and may lead to further surgery, radiation, or closer follow-up.
Lymph nodes
Lymph nodes are small immune organs found throughout the body. Tumor cells can travel from the skin to nearby lymph nodes through lymphatic channels; when tumor cells are found in a node, this is called a lymph node metastasis. Merkel cell carcinoma usually reaches the sentinel lymph node (the first node that receives drainage from the area of the tumor) before spreading to other nodes, so this node is often sampled even when no enlarged nodes can be felt. When the tumor is on the head or neck, nodes may be removed together in a procedure called a neck dissection (removal of the lymph nodes from one side of the neck).
Your report should state how many lymph nodes were examined and how many contain tumor. Nodes that contain tumor are called positive, and those without tumor are called negative. Pathologists often use immunohistochemistry to detect very small numbers of tumor cells in a node. Lymph node findings are used to determine the nodal stage.
In-transit metastasis
An in-transit metastasis is a deposit of tumor cells found in the skin or soft tissue somewhere between the original tumor and the nearby lymph nodes. In-transit metastases are important because they indicate more advanced disease, they raise the nodal stage, and they are associated with a higher risk of further spread.
Biomarker and molecular testing
Biomarkers are features of the tumor, often proteins or genetic changes, that provide information beyond the diagnosis itself, such as how the cancer is likely to behave or which treatments may help. For Merkel cell carcinoma, the most useful biomarker information comes from the tumor’s viral status and its overall molecular profile.
Merkel cell polyomavirus (MCPyV) status
The tumor is often tested for Merkel cell polyomavirus, usually with an immunohistochemistry stain for a viral protein called large T antigen. The report describes the result in one of two ways:
- Positive (virus-associated) — The stain detects the viral protein. The report may say “positive for Merkel cell polyomavirus” or “large T antigen positive.” These tumors usually carry few other genetic changes and generally have a somewhat more favorable outlook.
- Negative — The stain does not detect the virus. The report may say “negative for Merkel cell polyomavirus” or “large T antigen negative.” These tumors are usually driven by ultraviolet (UV) damage instead.
Viral status is used mainly as prognostic information and in research, rather than to choose a specific drug.
Tumor mutation profile
Some tumors are also examined with molecular methods that look at the genetic changes inside the tumor cells. The findings tend to fall into two patterns that mirror the viral status:
- Virus-positive tumors — Usually carry only a small number of mutations.
- Virus-negative tumors — Usually carry many mutations caused by UV damage, often involving genes called TP53 and RB1. A large number of mutations (a high tumor mutation burden) is one of the features that can make a cancer more visible to the immune system.
Importantly, the immunotherapy drugs used for advanced Merkel cell carcinoma are not chosen on the basis of a PD-L1 test or any other single biomarker; eligibility is based on the diagnosis and the stage of the disease. You can read more about biomarker testing in the Biomarkers section of this site.
Pathologic stage (pTNM)
The pathologic stage describes how advanced the cancer is, based on the tissue removed at surgery. Merkel cell carcinoma is staged using the TNM system of the AJCC (American Joint Committee on Cancer), 8th edition, which combines the size and extent of the tumor (T), spread to lymph nodes or in-transit metastases (N), and spread to distant organs (M). The M category is determined by imaging rather than by the pathologist. Higher stage numbers indicate more advanced disease.
Tumor stage (pT)
- pT1 — Tumor is 2 cm or smaller.
- pT2 — Tumor is larger than 2 cm but 5 cm or smaller.
- pT3 — Tumor is larger than 5 cm.
- pT4 — Tumor has grown into deeper structures such as bone, muscle, the tough tissue covering muscle (fascia), or cartilage.
Nodal stage (pN)
- pN0 — No tumor cells are found in the lymph nodes.
- pN1 — Tumor cells are found in one or more lymph nodes.
- pN2 — In-transit metastases are present, but no tumor is found in the lymph nodes.
- pN3 — Both lymph node metastases and in-transit metastases are present.
- pNX — The lymph nodes could not be assessed.
What is the prognosis?
The outlook for Merkel cell carcinoma depends strongly on the stage at diagnosis. Estimated five-year survival rates are about 50% when the cancer is limited to the skin, about 35% when it has reached regional lymph nodes, and about 15% when it has spread to distant organs. Merkel cell carcinoma responds well to radiation therapy, which is often used to control the disease, and immunotherapy has substantially improved outcomes for people with advanced disease compared with older treatments.
Several features in the pathology report are associated with a higher risk that the cancer will return or spread:
- Higher stage — Spread to lymph nodes or distant organs is the strongest predictor of a worse outcome.
- Larger size and deeper invasion — Bigger and deeper tumors are more likely to spread.
- Infiltrative growth pattern — Associated with a higher risk of recurrence and spread.
- Non-brisk tumor-infiltrating lymphocytes — A weaker immune response around the tumor.
- Lymphovascular invasion — Indicates the tumor has reached vessels that can carry cells elsewhere.
- In-transit metastases — Indicate more advanced disease.
- Virus-negative tumor — Tumors driven by UV damage tend to have a less favorable outlook than virus-positive tumors.
- Weakened immune system — Associated with a higher risk of recurrence and spread.
What happens after the diagnosis?
Treatment for Merkel cell carcinoma is usually coordinated by a team that may include a dermatologist, a surgical oncologist, a radiation oncologist, a medical oncologist, and a pathologist. The plan depends on the size and location of the tumor and on whether the cancer has spread.
For tumors that have not spread, the first step is usually surgery to remove the primary tumor with a margin of normal tissue. A sentinel lymph node biopsy is commonly performed at the same time, even when no enlarged nodes can be felt, to check for microscopic spread. Because Merkel cell carcinoma is sensitive to radiation, radiation therapy is often given after surgery to the tumor site and sometimes to the nearby lymph nodes to lower the risk of the cancer returning; radiation can also be the main treatment when surgery is not possible.
When the cancer has spread to lymph nodes or distant organs, the medical oncology team may consider immunotherapy, a type of treatment that helps the immune system attack the cancer. Drugs that block the PD-1 or PD-L1 pathway, such as avelumab, pembrolizumab, and retifanlimab, have become the main treatment for advanced Merkel cell carcinoma and have improved outcomes compared with the chemotherapy options used in the past. After treatment, close follow-up with skin and lymph node examinations and imaging is important because Merkel cell carcinoma can return; in people with virus-positive tumors, blood tests that measure antibodies against the Merkel cell polyomavirus are sometimes used to help monitor for recurrence.
Questions to ask your doctor
- How large was the tumor, and how deeply had it grown into the skin?
- Was my tumor tested for Merkel cell polyomavirus, and was it virus-positive or virus-negative?
- What was the growth pattern, and were tumor-infiltrating lymphocytes brisk or non-brisk?
- Was lymphovascular invasion seen?
- Were the surgical margins negative, close, or positive?
- If the margins were positive, do I need more surgery or radiation?
- Was a sentinel lymph node biopsy done, and did any lymph nodes contain cancer?
- Were any in-transit metastases found?
- What is the stage of my cancer, and what does that mean for my treatment?
- Will I need radiation therapy, immunotherapy, or both?
- How often will I need follow-up examinations and imaging?
- Do I have any conditions, such as a weakened immune system, that affect my risk or my treatment?
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