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Merkel cell carcinoma is a rare cancer, but its incidence and mortality are increasing.
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Most Merkel cell carcinoma tumors are linked to the common Merkel cell Polyomavirus.
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Novel disease detection and monitoring could take advantage of Merkel cell Polyomavirus T-antigen oncoproteins, which have been found to correlate with disease activity.
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Ultraviolet radiation exposure and immunosuppressed state are important risk factors for Merkel cell carcinoma.
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Immunotherapy with programmed cell death
Updates on Merkel Cell Carcinoma
Section snippets
Key points
Epidemiology
MCC incidence is highest in the eighth decade of life.2, 12, 13, 19, 20, 21, 22 Countries with growing percentages of the population more than 65 years old are likely to see an increase in the incidence of MCC in the coming years. This increase has been linked to prolonged exposure to risk factors that are associated with MCC,20, 23 as well as an altered immune system.3, 18, 24, 25, 26
UV radiation is a risk factor for MCC.2, 8, 27 Tumors commonly appear on areas of skin with significant UV
Merkel Cell Polyomavirus
Nearly 80% of MCC in the United States and other northern hemisphere countries is associated with the ubiquitous MCPyV.1, 43 In contrast, only about 25% of MCC in Australia has been attributed to MCPyV.4, 44 The MCPyV integrates its DNA into the host cells’ DNA, which results in aberrant oncogenic gene expression.45 The retinoblastoma tumor suppressor protein (RB1) is inhibited by MCPyV integration, thereby causing MCC cell proliferation.46 This pathway is specific to MCPyV but is not the only
Clinical Appearance
MCC tumors are usually firm, painless, and rapidly growing, on the sun-exposed areas of the head, neck, or extremities2 (Fig. 1). These tumors can be various shades of red, pink, or flesh colored.2 The AEIOU (asymptomatic, expanding rapidly, immune suppression, older than 50 years, and UV-exposed location on a person with lighter skin color) mnemonic is often used as a clinical tool to aid in diagnosis, because 89% of patients with MCC have at least 3 of the 5 characteristics.2
Histology, Pathology, and Immunohistochemistry
The diagnosis of
Patient-Related Characteristics
MCC is a highly aggressive tumor. Older age, male gender, black race, advanced stage or increasing number of metastatic sites, primary tumor on the head/neck or trunk, and immunosuppression are associated with lower survival rates.12, 14, 82, 83, 84, 85 Pathologic, rather than clinical, node involvement is associated with poorer prognosis.10, 83, 86, 87, 88
Patients living in areas with an increased density of dermatologists were more likely to survive than those in areas without dermatologists.
Surgery
MCC requires a multidisciplinary approach to care, which involves dermatologists, medical and radiation oncologists, pathologists, and surgeons.120 The goal of surgical treatment is negative histologic margin.16 Surgical excision with 1-cm to 2-cm margins remains the preferred first step in the management and treatment of the primary tumor.16, 50 Mohs micrographic surgery (MMS) can be considered when tissue sparing and/or a more comprehensive histologic evaluation of margins is required.121, 122
JAVELIN Merkel 200 Trial
Avelumab, a human monoclonal antibody that inhibits PD-L1, has been approved by the US Food and Drug Administration (FDA), European Union, Canada, and Japan for the treatment of advanced MCC based on the JAVELIN Merkel 200 trial,18 a phase II, open-label, multicenter trial investigating the clinical activity and safety of avelumab in patients with MCC. Twenty-eight of 88 patients with stage IV MCC who had previously received chemotherapy, or 31.8% (95% confidence interval [CI], 21.9–43.1), had
Summary
In summary, MCC is a rare and aggressive cancer with increasing incidence. There have been many advances in the last several decades in the etiology and management of MCC, but much about its natural history and most effective treatment remains unknown. Surgical excision with margins of 1 to 2 cm remains the recommended first-line therapy for early-stage disease, but larger, prospective studies are needed to confirm the potential benefits and role of MMS. Robust evidence supporting immunotherapy
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Cited by (19)
Merkel cell carcinoma: epidemiology, clinical features, diagnosis and treatment of a rare disease
2023, Anais Brasileiros de DermatologiaDiagnosis and treatment of Merkel cell carcinoma: European consensus-based interdisciplinary guideline – Update 2022
2022, European Journal of CancerCitation Excerpt :The most frequent anatomic sites of MCC are the sun-exposed areas of head and neck (29–43.9%) and the extremities (36.9–45%), whereas less than 5–10% of MCCs develop on partially sun-protected areas (abdomen, thighs and hair-bearing scalp) or highly sun-protected areas (buttocks). Extra-cutaneous sites such as vulva, vagina, oral mucosa [51], parotid gland, submandibular gland or nasal cavity are very rarely involved (around 0.5%) [31,50,52,53]. In some cases, the primary tumour (pT) site is unknown and the disease presents metastatic disease to lymph nodes or distant organs (0.8–14%) [31].
New insights into Merkel cell carcinoma
2021, Piel
Disclosure: The authors have nothing to disclose.