Merkel cell carcinoma !

A rare, fast-growing skin cancer that looks like a painless red or purple lump on sun-exposed skin of older people and spreads early to lymph nodes.

Updated 2026-11-01

Structures involved

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Why it happens

What it is

An aggressive primary neuroendocrine carcinoma of the skin. It appears as a firm, painless, rapidly growing nodule, most often on the head, neck or limbs of older or immunosuppressed people, and spreads early to regional lymph nodes.

Who gets it

Rare, but incidence has risen sharply in recent decades with population ageing and more immunosuppression. Median age at diagnosis is around 65–75; it is more common in men and in fair-skinned people. In Latin America it is less common than in Australia or the US, but intense equatorial UV exposure at altitude, as in the Colombian Andes, and the growing number of transplant recipients and people with HIV are relevant.

Causes

Merkel cell polyomavirus integrated into the tumour genome (most cases in the Northern Hemisphere)
Ultraviolet DNA damage in virus-negative tumours (more common in very sunny regions)

Risk factors

Age over 50
Fair skin and chronic sun exposure
Immunosuppression: organ transplant, HIV, chronic lymphocytic leukaemia and other blood cancers, immunosuppressive drugs
Previous PUVA therapy
Previous skin cancers

Pathophysiology

In virus-positive tumours the integrated polyomavirus produces large T antigen, which blocks the retinoblastoma tumour suppressor and drives cell division. Virus-negative tumours carry a heavy UV mutation load, often in TP53 and RB1. Both types are highly immunogenic, which explains why the cancer is more common with weak immunity and why it responds to immune checkpoint inhibitors. The tumour cells behave like neuroendocrine cells and spread rapidly through lymphatics.

Classification

Virus-positive versus UV-associated (virus-negative)
AJCC TNM stage: local disease, regional node disease, distant metastases
Clinically occult (found only on sentinel node biopsy) versus clinically detected nodal disease

Symptoms and signs

A firm, painless, shiny red, pink or violet skin nodule
Rapid growth over weeks to a few months
Most often on sun-exposed head and neck, including the eyelids, or on the limbs
Enlarged regional lymph nodes
The AEIOU features: Asymptomatic, Expanding rapidly, Immunosuppression, Older than 50, UV-exposed skin

Diagnosis

Clinical: Any rapidly growing, painless skin nodule in an older or immunosuppressed person needs a biopsy; it is often mistaken for a cyst or benign lesion. Examine all regional lymph node basins.
Tests: Skin biopsy shows small round blue cells; immunohistochemistry is positive for cytokeratin 20 (often in a perinuclear dot pattern) and neuroendocrine markers, and negative for TTF-1, which separates it from metastatic small-cell lung cancer. Sentinel lymph node biopsy stages clinically negative nodes. Merkel cell polyomavirus antibody levels can help follow virus-positive patients.
Imaging: PET-CT or CT of the chest, abdomen and pelvis (and neck when relevant) for staging and to exclude a lung primary; ultrasound of lymph node basins.

Differential diagnosis

Basal cell carcinoma
Cutaneous squamous cell carcinoma
Amelanotic melanoma
Cutaneous lymphoma
Metastatic small-cell lung carcinoma
Benign cyst or lipoma

Goal of treatment

Remove local disease with clear margins, treat the regional nodes and control advanced disease with immunotherapy, with close follow-up because early relapse is common.

Treatment

Surgical: Wide local excision of the primary tumour with clear margins (Mohs surgery is an alternative in some sites), together with sentinel lymph node biopsy.
Procedure: Radiotherapy to the tumour bed and node basins after surgery for higher-risk disease, or as the main treatment when surgery is not possible.
Medical: Immune checkpoint inhibitors (anti-PD-1 or anti-PD-L1 antibodies) are first-line for advanced or metastatic disease; chemotherapy has a short-lived benefit and is used less.
Follow-up: Frequent skin and lymph node examination and imaging in the first two to three years, when most recurrences occur; viral antibody levels in virus-positive patients; reducing immunosuppression when possible.

Complications

Local recurrence
Regional lymph node metastases
Distant metastases to liver, bone, lung and brain
Immune-related adverse effects of checkpoint inhibitors

Prognosis

More lethal than melanoma stage for stage. Small, node-negative tumours have high survival, while nodal and especially distant disease carry a much worse outlook; most recurrences appear within two years. Immunotherapy has improved survival in advanced disease.

Prevention

Sun protection
Regular skin examination in transplant recipients and other immunosuppressed people

Test yourself

Think of the answer, then tap the question to see it.

Which virus is linked to most Merkel cell carcinomas?

Merkel cell polyomavirus.

What immunostain pattern helps identify Merkel cell carcinoma?

Cytokeratin 20 positivity, often perinuclear dot-like, with TTF-1 negativity.

What does the AEIOU mnemonic describe?

Asymptomatic, Expanding rapidly, Immunosuppression, Older than 50, UV-exposed site: typical features of Merkel cell carcinoma.

What systemic treatment is first-line for metastatic Merkel cell carcinoma?

Immune checkpoint inhibitors (anti-PD-1 or anti-PD-L1 antibodies).

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Educational information, not medical advice. For any symptom, see a health professional.

Sources: Merkel Cell Carcinoma Treatment (PDQ®)–Health Professional Version (National Cancer Institute, 2025).

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Representative model, for educational purposes only.

Skin highlighted on the Durgical 3D model