Merkel cell carcinoma is a rare, aggressive neuroendocrine skin cancer with high propensity for local recurrence and early metastasis. It is associated with Merkel cell polyomavirus (MCPyV) integration in ~60–80% of cases and/or UV-induced mutations. Clinically, it presents as a rapidly growing, firm, painless, red-violet nodule on sun-exposed skin in older or immunosuppressed patients. Management includes wide excision, sentinel lymph node biopsy, consideration of adjuvant radiation, and PD-1/PD-L1 checkpoint inhibitors for advanced disease.
Epidemiology and Risk Factors
- Incidence rising; median age ~70; higher in fair skin.
- Risks: UV exposure, immunosuppression (transplant, hematologic malignancies, HIV), MCPyV seropositivity.
- In skin of color, lesions may be diagnosed later; vigilance is needed.
Clinical Features (AEIOU mnemonic)
- Asymptomatic, Expanding rapidly, Immune suppression, Older than 50, UV-exposed site.
- Firm, dome-shaped, shiny, red-to-violaceous nodule; may ulcerate; regional nodes can be involved early.
Diagnosis
- Prompt biopsy for any suspicious rapidly growing nodule.
- Histopathology: dermal/subcutaneous sheets of small blue round cells; high mitotic rate; frequent lymphovascular invasion.
- Immunohistochemistry: CK20 perinuclear dot positivity; neuroendocrine markers (chromogranin, synaptophysin); negative TTF-1 (helps distinguish from small-cell lung carcinoma).
- MCPyV status by IHC (CM2B4) or PCR may have prognostic value.
Staging and Workup
- Clinical node exam and imaging (PET/CT ± brain MRI) for staging; occult nodal disease is common.
- Sentinel lymph node biopsy recommended for clinically node-negative patients; influences adjuvant therapy.
- AJCC 8th staging incorporates tumor size, nodal status, and metastases.
Management
- Local and regional
- Wide local excision with 1–2 cm margins down to fascia where anatomically feasible; reconstruct after SLNB.
- SLNB at time of primary surgery; completion lymph node dissection is controversial; nodal RT may be preferred in some settings.
- Adjuvant radiation therapy:
- Primary site RT reduces local recurrence, especially for positive/close margins, lymphovascular invasion, head/neck location, or immunosuppression.
- Nodal basin RT for positive SLN or high-risk features.
- Systemic therapy
- Immune checkpoint inhibitors are standard for unresectable/metastatic MCC:
- Avelumab (PD-L1), pembrolizumab (PD-1), nivolumab (PD-1) show high response rates and durability.
- Cytotoxic chemotherapy (platinum/etoposide) can induce rapid responses but is not durable; reserved for ICI-refractory or rapid control needs.
- Clinical trials encouraged.
- Surveillance
- Close follow-up every 3 months for the first 2 years, then every 3–6 months to year 3, then every 6–12 months; incorporate nodal exams and imaging per risk.
- Educate on self-exam and prompt reporting of new nodules or lymphadenopathy.
Prognosis
- Worse than melanoma stage-for-stage; 5-year overall survival varies widely by stage.
- Virus-positive tumors may have better prognosis; immunosuppression portends poorer outcomes.
References (recent guidelines and key reviews)
- NCCN guidelines for MCC, 2022–2024.
- Clinical trials of avelumab, pembrolizumab, nivolumab in advanced MCC, 2021–2024.
- Surgical and radiation oncology best practices in MCC, 2021–2024.