Merkel cell carcinoma

Also known as: MCC; trabecular carcinoma

Merkel cell carcinoma is a rare, aggressive cutaneous neuroendocrine tumour with significant metastatic potential. Around 70–80% of cases in contemporary series are driven by Merkel cell polyomavirus; the remainder are UV-induced. Multimodality management is essential.

Current Last reviewed 10 March 2026

Key points

The AEIOU mnemonic prompts suspicion: Asymptomatic, Expanding rapidly, Immunosuppressed, Older than 50, UV-exposed fair skin.

Wide local excision with 1–2 cm margin plus SLNB for clinically node-negative disease is the surgical standard.

Adjuvant radiotherapy to the primary and draining nodal basin reduces locoregional recurrence.

Anti-PD-(L)1 is first-line for metastatic / locally advanced MCC. Avelumab is NICE-commissioned (TA691 for untreated metastatic MCC; TA517 history for metastatic MCC after chemotherapy). Pembrolizumab has phase 2 evidence in advanced MCC (KEYNOTE-017), but no NICE pembrolizumab MCC TA was identified on live checking; confirm any access route before use. Responses are durable in a substantial proportion.

Five-year OS ~75% local, ~60% nodal, ~20% distant — stage-dependent and improving with immunotherapy.

Clinical features

MCC typically presents as a rapidly enlarging, painless, firm, red or violaceous nodule on sun-exposed skin of older patients. Head and neck (~50%) and extremities most common. Ulceration is unusual at presentation.

AEIOU risk features

Asymptomatic
Expanding rapidly (weeks–months)
Immunosuppressed
Older than 50
UV-exposed / fair skin

Three or more features warrant urgent biopsy.

Diagnosis

Histology required. Immunohistochemistry is pathognomonic:

CK20 positive with paranuclear dot-like pattern.
Neuroendocrine markers: synaptophysin, chromogranin, CD56 positive.
TTF-1 negative — essential to exclude metastatic small-cell lung cancer.

Baseline staging imaging is routine — PET-CT preferred where available, with MRI brain if symptomatic.

Management

Guideline UK national guidance Trial randomised trial NICE TA NICE Technology Appraisal Consensus expert opinion Local MDT MDT-dependent Full key →

Localised disease

Guideline Wide local excision with 1–2 cm margin to fascia is the standard. Mohs has a niche role at selected facial sites where tissue conservation matters, performed at specialist centres with appropriate frozen-section / IHC interpretation and without compromising SLNB workflow — it is not the routine standard.
Local MDT SLNB for clinically node-negative (~30% positive).
Consensus Adjuvant radiotherapy to primary site (reduces local recurrence ~3× in most series).
Consensus Adjuvant nodal radiotherapy for SLN-positive where completion dissection is declined.

Metastatic disease

NICE TA Avelumab — NICE TA691, first-line.
Trial Pembrolizumab — alternative PD-1.
Consensus Platinum-etoposide — rapid short-lived responses; reserve for ICI-refractory.

UK GuidelineMDT mandatory

Every MCC case should be discussed at the local specialist skin cancer MDT with input from dermatology, plastic surgery, clinical oncology and medical oncology given rarity and treatment complexity.

Follow-up

After radical treatment: clinical examination every 3–6 months for the first 3 years, then every 6 months until year 5.
After 5 years: annual lifelong general physical examination including complete skin check.
Each review should include full-skin examination, scar / in-transit field assessment and regional lymph-node examination.
Cross-sectional imaging may be proposed for higher-risk patients, but should be MDT-led rather than a fixed interval for everyone.

References

Gauci ML et al. EADO/EORTC/UNITE. Diagnosis and treatment of Merkel cell carcinoma: European consensus-based guidelines. Eur J Cancer; 2022.

NICE TA691. Avelumab for untreated metastatic Merkel cell carcinoma. London: NICE; 2021.

Nghiem PT et al. Three-year survival, correlates and salvage therapies with first-line pembrolizumab for advanced MCC. J Immunother Cancer; 2021.