Merkel cell carcinoma

Merkel cell carcinoma (MCC) is an aggressive neuroendocrine cancer of the skin. It often presents as a rapidly enlarging, painless red, violet or skin-colored nodule. A biopsy is needed: appearance alone can resemble a cyst, lymphoma, another skin cancer or a metastasis.

Pathologists combine cell appearance with immunostains such as CK20 and neuroendocrine markers, and use other markers and imaging when needed to exclude a different primary, including small cell lung cancer. No single stain should be treated as infallible. This diagnosis should not be managed as a low-grade gastrointestinal neuroendocrine tumor.

MCC can arise through Merkel cell polyomavirus-related or UV-related biological pathways. Virus-negative disease is still MCC. Tumor virus testing, a blood antibody test and PD-L1 staining answer different questions; a negative result on one does not automatically exclude immunotherapy.

Tell the team about an organ transplant, chronic lymphocytic leukemia, HIV, autoimmune disease or immune-suppressing medicines. These can affect recurrence risk, treatment safety and follow-up. Changes to immune suppression require the relevant treating specialist; stopping medicines independently can be dangerous.

The work-up includes the entire skin and draining lymph-node regions, with imaging to look for disease beyond what can be felt. PET-CT or CT is selected according to availability and the clinical question; neurological symptoms may warrant brain imaging. Suspicious nodes need appropriate sampling.

When nodes are not clinically involved, sentinel lymph-node biopsy is usually planned with definitive local surgery because it can find microscopic spread that scans miss. It should be discussed before a wide excision or reconstruction alters lymphatic drainage. A negative result is reassuring but its reliability can be reduced by complex drainage or immune suppression.

Sometimes MCC is found in a lymph node without an identifiable skin primary. That does not automatically mean distant metastatic disease; the nodal location and complete work-up determine staging and whether regional curative treatment is possible.

Localized MCC is commonly treated with excision and consideration of radiotherapy to improve local control. The margin, reconstruction and radiation field should be planned together, especially near an eye, nose or joint. If surgery would be unsuitable, definitive radiation can be an alternative in selected patients.

Microscopic sentinel-node involvement and bulky clinically involved nodes are different situations. Nodal radiation, dissection or a combination is selected according to burden, extranodal extension, drainage and morbidity. Lymphedema risk and rehabilitation deserve discussion before treatment.

Omitting postoperative radiation is a selective decision for very low-risk disease, not a default for every small tumor. A recent low-risk database study did not find an overall-survival association, but an observational survival analysis cannot establish that radiation offers no local-control benefit for an individual.

In STAMP, postoperative pembrolizumab did not significantly improve the broad relapse-free-survival endpoint, although results favored fewer distant recurrences. The 2026 update reported encouraging MCC-specific outcomes and exploratory findings about radiation sequencing. These analyses do not prove that every patient should receive treatment or that changing radiation timing itself causes better survival.

The 2026 ADAM presentation studied postoperative avelumab in node-positive disease, with most patients also receiving radiation. Fewer MCC relapses were observed, but the primary relapse-free-survival comparison was not statistically significant. Earlier ADMEC-O nivolumab results also suggested benefit with uncertainty and added toxicity. These are important discussions for higher-risk patients, with local guidance and trial access considered.

An advanced-disease drug approval is not automatically an adjuvant approval. The decision should explain the expected absolute benefit, immune risks, treatment burden and what is known about long-term survival. Routine postoperative cytotoxic chemotherapy is not supported as a substitute.

For suitable patients whose disease cannot be cured by local treatment, PD-1 or PD-L1 blockade is generally central to systemic treatment. Current US MCC indications include avelumab for metastatic disease in adults and patients aged 12 or older, pembrolizumab for recurrent locally advanced or metastatic disease in adults and children, and retifanlimab for adults with metastatic or recurrent locally advanced disease.

Neither a positive PD-L1 score nor virus positivity is a prerequisite for these US MCC indications. Avelumab has infusion-reaction precautions; all checkpoint drugs require immune-toxicity monitoring. An organ transplant or serious autoimmune history may change the balance markedly.

Country-specific labels matter. The UK approved retifanlimab in 2026 as first treatment for eligible adults with advanced disease that has spread or returned and cannot be cured by surgery or radiation. Regulatory approval does not by itself confirm local funding, stock or suitability for a particular patient.

Reassessment should distinguish an isolated growing site from widespread progression and review whether the original drug was stopped for toxicity or true resistance. Biopsy or repeat imaging may be appropriate when the clinical picture is unclear. Local radiation or surgery can sometimes address a limited problem while a broader treatment plan is reconsidered.

Nivolumab plus ipilimumab has shown activity in a small phase 2 study, including some patients previously treated with PD-1 or PD-L1 therapy, but serious immune toxicity was substantial. Adding stereotactic radiation did not improve the study's response endpoint. This supports a specialist or trial discussion rather than a promise that dual immunotherapy, or adding radiation, will overcome resistance.

Chemotherapy may be considered when immune treatment is unsuitable or after other options, often with the goal of rapid symptom control. Responses can be short-lived, so toxicity, expected duration of control and trial access should be discussed together.

A 2026 phase 2 study of lenvatinib plus pembrolizumab before local treatment reported pathological complete responses in selected resectable MCC. It was a small, single-center study, with frequent significant toxicity, including hypertension; two patients did not reach their planned surgery because of progression or toxicity.

This is a research-supported discussion, not an instruction to add a targeted drug to every patient's immunotherapy. If a preoperative approach is proposed, clarify the protocol, surgical timing, blood-pressure and toxicity monitoring, and the fallback plan. A disappearing skin lump does not justify abandoning definitive treatment without specialist reassessment.

A tumor-informed ctDNA test looks for DNA changes identified in an individual's cancer. Prospective studies show that a positive result after treatment can identify increased recurrence risk and may precede visible recurrence. It can be relevant to both virus-positive and virus-negative MCC, but requires suitable tumor material and access to an appropriate assay.

A negative result is reassuring for the period studied, not a lifetime guarantee or a reason to ignore symptoms. A positive result should prompt a coordinated assessment; evidence that a marker predicts recurrence is not the same as proof that immediately starting a particular drug improves survival.

Antibodies to Merkel polyomavirus oncoproteins are a different blood marker. They are most useful for serial surveillance when detectable near diagnosis. Rising levels can prompt closer assessment. Routine antibodies showing past viral exposure are not the same test, and a patient without measurable oncoprotein antibodies needs another surveillance strategy.

Follow-up is closest in the first few years, when recurrence risk is highest, and includes the treated skin, other skin sites and regional nodes. The team selects imaging and blood-marker use according to stage, immune health and previous results. Skin self-checks and sun protection remain useful even after treatment ends.

Report a new lump or node, persistent unexplained pain, cough or neurological change. During or after immunotherapy, significant diarrhea, breathlessness, jaundice or profound weakness also need prompt contact with the treating team because immune toxicity can resemble other illnesses.

Bring pathology and immunostain results, sentinel-node details, scan images, surgery and radiation records, drug history and any baseline antibody or ctDNA results. Ask whether local cure remains realistic, what the nodal result changes, and which recommendations are standard treatment versus an evolving postoperative or preoperative strategy.