Case 1: Merkel cell carcinoma
By Simon Naseri, MD, Mike Mikkelsen Lorenzen, MD and Magnus Balslev Avnstorp, MD
Pathophysiology
Merkel cell carcinoma, first described in 1972 by Toker, is a rare and aggressive neuroendocrine carcinoma of the skin. MCC is caused by UV-radiation (in 24 %) and/or the merkel cell polyoma virus (MCV, in 76 %). The incidence of MCC is 0.22 per 100’000 person years (1995-2006). Risk factors for developing MCC include immunosuppression, as seen in patients with chronic lymphatic leukemia (30-fold increase), the human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS, 13-fold increase) and organ transplants recipients (10-fold increase). Patients diagnosed with MCC have a 5-year overall survival of 40 %, making it more deadly than melanoma.
MCC is characterized by its aggressive local growth and high rate of metastasis, as 35 % of patients initially present with metastatic disease. Merkel cell polyomavirus is responsible for 74 % of MCCs and induce carcinogenesis by incorporating its viral DNA into the host DNA. The viral DNA encodes oncoproteins that inhibit tumor suppressor function and initiates carcinogenesis.
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Treatment and surgical margins
All MCC-patients should be evaluated individually in multidisciplinary tumor board consultations.
Primary tumor management
- Radical excision with a margin of 1-2 cm to the fascia.
- Adjuvant radiotherapy (RT) is recommended in patients with:
- Large primary tumor (> 1 cm diameter)
- Lymphovascular invasion
- Chronic immunosuppression (i.e., lymphoma/leukemia)
- Positive excision margin status
- Positive sentinel lymph node biopsi
Regional lymph node involvement
- Therapeutic radical lymph node dissection is recommended in case of lymph node involvement
- Adjuvant radiotherapy may be considered in case of extracapsular disease.
Distant metastatic disease
- Immunotherapy with PD/PD-L1 inhibitors such as avelumab and pembrolizumab are recommended as first-line treatment.
- Chemotherapy with cisplatin or carboplatin in combination with etoposide is recommended as second-line treatment.