Your pathology report for Merkel cell carcinoma

by Allison Osmond, MD FRCPC
January 8, 2026

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Merkel cell carcinoma is a rare but aggressive type of skin cancer. It is a type of neuroendocrine tumour, meaning it starts from neuroendocrine cells in the skin. Neuroendocrine cells are specialized cells that help the body send signals by releasing chemical messengers in response to nerve signals. Because of how these cells function, Merkel cell carcinoma tends to grow quickly and has a higher risk of spreading than many other skin cancers.

This article explains the pathology report for Merkel cell carcinoma, including how it is diagnosed, what features pathologists look for, and how these findings relate to prognosis and treatment.

Where does Merkel cell carcinoma develop?

Merkel cell carcinoma arises in the skin, most often on sun-exposed areas. The most commonly affected sites are:

• The head and neck.

• The arms and legs.

• The trunk.

In some patients, cancer is first found in lymph nodes or other sites without an obvious skin tumour. In these cases, the original skin lesion may have regressed (disappeared) on its own.

What are the symptoms of Merkel cell carcinoma?

Merkel cell carcinoma usually appears as a rapidly growing, firm, flesh-coloured to reddish-purple (violaceous) lump or plaque on the skin. It is often painless and may initially resemble more common skin conditions such as a cyst, basal cell carcinoma, or squamous cell carcinoma.

Because this tumour grows quickly, it may increase in size over weeks to months. Some patients are diagnosed only after the cancer has already spread to nearby lymph nodes or distant organs.

Who gets Merkel cell carcinoma?

Merkel cell carcinoma most often affects older adults, with a median age at diagnosis of about 75 years. It is uncommon in people younger than 50 years.

The disease is much more common in people with lighter skin, and its incidence is higher in regions with intense sun exposure. The risk is also increased in people with weakened immune systems, including those with HIV infection, organ transplant recipients, and patients with certain blood cancers such as chronic lymphocytic leukemia.

What causes Merkel cell carcinoma?

Two major factors are strongly linked to the development of Merkel cell carcinoma:

• Ultraviolet (UV) radiation: Long-term sun exposure damages DNA in skin cells. In some tumours, this leads to many genetic mutations typical of UV damage.
• Merkel cell polyomavirus (MCPyV): In many cases, a virus called Merkel cell polyomavirus becomes integrated into the DNA of tumour cells. This viral integration drives tumour growth through viral proteins that interfere with normal cell-cycle control.

Some tumours are virus-positive, while others are virus-negative and driven primarily by UV-related DNA damage. These two groups have different genetic profiles and can behave differently.

Advanced age and immunosuppression increase the risk of both virus-associated and UV-associated disease.

How is the diagnosis made?

The diagnosis is made by examining a skin biopsy or surgical specimen under the microscope and confirming the findings with immunohistochemistry. Imaging studies are then used to stage the disease.

Microscopic (pathologic) features

Under the microscope, Merkel cell carcinoma typically appears as a dense collection of blue-appearing tumour cells in the dermis and sometimes the subcutaneous tissue. The tumour may grow as a well-defined nodule or show an infiltrative pattern.

The tumour cells are small to medium in size and have minimal cytoplasm, making the nuclei appear crowded. A hallmark feature is fine “salt-and-pepper” chromatin within the nuclei, typical of neuroendocrine tumours. The cells divide rapidly, so mitotic figures and apoptotic bodies are usually numerous.

Tumour cells may form solid sheets, nests, or occasionally a trabecular (cord-like) pattern. Growth into lymphatic channels is common. In some cases, tumour cells are also found in the epidermis (epidermotropic Merkel cell carcinoma). Rarely, the tumour may be confined to the epidermis or hair follicles (Merkel cell carcinoma in situ).

Most cases arise on their own, but some Merkel cell carcinomas develop together with squamous cell carcinoma. In these combined tumours, the neuroendocrine cancer cells are believed to originate from the squamous cancer.

Immunohistochemistry

Immunohistochemistry uses special stains to detect proteins in tumour cells and is essential for confirming the diagnosis.

Merkel cell carcinoma typically expresses:

• Neuroendocrine markers, such as INSM1, chromogranin, synaptophysin, and CD56.

• Epithelial markers, including cytokeratins.

A classic and very helpful finding is perinuclear dot-like staining for CK20 and/or neurofilament. This pattern is highly characteristic of Merkel cell carcinoma and helps distinguish it from other cancers.

Most tumours are negative for TTF-1, which helps exclude metastatic small cell lung carcinoma. Testing for Merkel cell polyomavirus large T antigen can identify virus-associated tumours and has prognostic significance.

Molecular testing

Molecular testing is not required for diagnosis but may be performed in selected cases.

• Virus-positive tumours usually have few genetic mutations.

• Virus-negative tumours often show many mutations, especially involving TP53 and RB1, reflecting UV-induced DNA damage.

Identifying virus status can help with prognosis and research-based treatment decisions.

Depth of invasion (tumour thickness)

Merkel cell carcinoma starts in the outer layer of the skin, called the epidermis. Depth of invasion describes how far the cancer cells have grown downward into the layers of tissue beneath the skin. This downward growth is called invasion.

Pathologists measure the depth of invasion from the skin surface to the deepest point where cancer cells are seen. This measurement is reported in millimetres (mm) and may also be referred to as tumour thickness in some pathology reports.

Depth of invasion is important because tumours that grow deeper into the skin are more likely to spread to lymph nodes or other parts of the body. This measurement is also used to help determine the pathologic tumour stage, which guides prognosis and treatment planning.

Tumour extension

As Merkel cell carcinoma grows, it can sometimes spread beyond the skin into deeper structures such as muscle, cartilage, or bone. When this happens, pathologists describe it as tumour extension.

Tumour extension into deeper tissues is important because it is associated with a higher risk of local recurrence (the tumour coming back in the same area) and a greater chance of spread to other parts of the body. Like depth of invasion, tumour extension is also used to help determine the tumour stage.

Tumour pattern of growth

The pattern of growth describes how the cancer cells are arranged when examined under the microscope.

In Merkel cell carcinoma, pathologists usually describe one of two main growth patterns:

• Nodular pattern: The cancer cells grow together in one or more compact clusters or nodules.

• Infiltrative pattern: The cancer cells spread out as thin strands or irregular lines that weave through the surrounding tissue. Under the microscope, this pattern can resemble a spider’s web.

Tumours with a nodular growth pattern are generally associated with a better prognosis, whereas an infiltrative pattern is associated with a higher risk of spread and recurrence.

Tumour-infiltrating lymphocytes

Lymphocytes are immune cells that help the body recognize and fight infections and cancer. In Merkel cell carcinoma, lymphocytes are often found in and around the tumour.

Their presence suggests that the immune system is attempting to recognize and control the cancer. Pathologists describe tumour-infiltrating lymphocytes in one of two ways:

• Brisk: Many lymphocytes are seen throughout and around the tumour.

• Non-brisk: Few lymphocytes are present around the tumour.

A brisk lymphocytic response is generally associated with a better prognosis, while non-brisk tumour-infiltrating lymphocytes are associated with a higher risk of aggressive behaviour.

What does lymphovascular invasion mean?

Blood travels through blood vessels, while another fluid called lymph travels through lymphatic channels. Lymph helps remove waste and carries immune cells that fight infection.

Cancer cells can use blood vessels and lymphatic channels as pathways to spread away from the original tumour. When cancer cells are found inside a blood vessel or a lymphatic channel, this is called lymphovascular invasion.

Lymphovascular invasion is important because cancer cells must first enter one of these vessels before they can spread to lymph nodes or distant organs such as the lungs. When lymphovascular invasion is present, the risk of metastasis is higher, and this information helps doctors assess prognosis and plan treatment.

Margins

A margin is the normal-looking tissue that surrounds the tumour and is removed along with it during surgery. Surgeons usually aim to remove the tumour with a rim of normal tissue to reduce the chance that cancer cells are left behind.

For Merkel cell carcinoma, pathologists typically examine:

• The peripheral margin, which is the skin around the tumour.

• The deep margin, which is the tissue beneath the tumour.

Margins are described as:

• Negative if no cancer cells are seen at the cut edge of the tissue, meaning the tumour was likely completely removed.

• Positive if cancer cells are present at the edge of the tissue, suggesting that some tumour may remain.

A positive margin is important because it is associated with a higher risk of the tumour returning to the same location after treatment and may influence decisions about additional surgery, radiation therapy, or closer follow-up.

Lymph nodes

Lymph nodes are small immune organs found throughout the body. They filter lymph fluid and help the immune system respond to infections and cancer.

Cancer cells can travel from the tumour to the lymph nodes through nearby lymphatic channels. When cancer cells are found in a lymph node, this is called a lymph node metastasis.

If the tumour is located on the head or neck, lymph nodes from the neck may be removed during surgery in a procedure called a neck dissection. The lymph nodes in the neck are grouped into areas called levels, numbered 1 through 5.

• Lymph nodes on the same side as the tumour are called ipsilateral.

• Lymph nodes on the opposite side are called contralateral.

The sentinel lymph node is the lymph node most likely to receive cancer cells first if the tumour spreads. For Merkel cell carcinoma, cancer usually spreads to the sentinel lymph node before reaching other lymph nodes.

All other nearby lymph nodes are called regional lymph nodes.

Your pathology report should specify:

• How many lymph nodes were examined.

• How many contain cancer cells.

Lymph nodes that contain cancer are called positive, while those without cancer are called negative.

Pathologists often use immunohistochemistry to help detect very small numbers of cancer cells in lymph nodes. Merkel cell carcinoma cells produce proteins called cytokeratins, and special stains can make these cells easier to see under the microscope.

Lymph node findings are used to determine the nodal stage, which is key to staging and treatment planning.

What does in-transit metastasis mean?

When cancer cells break away from the primary tumour and travel to another location, this is called metastasis. Cancer cells often spread first to nearby lymph nodes, which is called lymph node metastasis.

In Merkel cell carcinoma, cancer cells can sometimes be found in the skin or soft tissue between the primary tumour and a nearby lymph node. These deposits are called in-transit metastases.

The presence of in-transit metastases is crucial because it indicates a more advanced disease. It increases the nodal stage and is associated with a worse prognosis compared with tumours that have not spread beyond the primary site.

What is the pathologic stage for Merkel cell carcinoma?

The pathologic stage describes how advanced the cancer is based on examination of tissue removed during surgery. Merkel cell carcinoma is staged using the TNM staging system, which looks at:

• T (tumour) – size and local extent of the primary tumour.

• N (nodes) – spread to lymph nodes or in-transit metastases.

• M (metastasis) – spread to distant organs.

In general, higher stage numbers mean more advanced disease and a worse prognosis.

Tumour stage (pT)

The tumour stage is based on tumour size and whether the cancer has grown into deeper tissues.

• T1 – The tumour is 2 cm or smaller.

• T2 – The tumour is larger than 2 cm but no larger than 5 cm.

• T3 – The tumour is larger than 5 cm but has not grown into deeper tissues.

• T4 – The tumour has grown into bone, muscle, fascia, or cartilage.

Nodal stage (pN)

The nodal stage describes spread to lymph nodes and in-transit metastases.

• pN0 – No cancer cells are found in lymph nodes.

• pN1 – Cancer cells are found in one or more lymph nodes.

• pN2 – Cancer cells are found as in-transit metastases but not in lymph nodes.

• pN3 – Cancer cells are found in both lymph nodes and in-transit metastases.

If no lymph nodes are examined, the nodal stage cannot be determined and is reported as pNX.

What is the prognosis for a person with Merkel cell carcinoma?

Merkel cell carcinoma is an aggressive cancer, but outcomes depend strongly on the stage at diagnosis.

Estimated 5-year survival rates are:

• About 50% for localized disease.

• About 35% when regional lymph nodes are involved.

• Around 15% when distant metastases are present.

Tumours that are Merkel cell polyomavirus–positive generally have a better prognosis than virus-negative tumours. Merkel cell carcinoma is sensitive to radiation therapy, which is often used to control the disease locally. Immunotherapy has significantly improved outcomes for patients with advanced disease.

Questions to ask your doctor

• Was my tumour tested for Merkel cell polyomavirus?
• Has the cancer spread to lymph nodes or other organs?
• What stage is my cancer, and what does that mean for treatment?
• Will I need radiation or immunotherapy?
• How often will I need follow-up examinations and imaging?