Merkel cell carcinoma of the head and neck: pathogenesis, current and emerging treatment options

Abstract

Merkel cell carcinoma (MCC) is a relatively uncommon, neuroendocrine, cutaneous malignancy that often exhibits clinically aggressive features and is associated with a poor prognosis. It typically presents as a painless, rapidly enlarging, dome-shaped red or purplish nodule in a sun-exposed area of the head and neck or upper extremities. Our understanding of MCC has increased dramatically over the last several years and the pathogenesis continues to be an area of active research. The etiology is likely multifactorial with immunosuppression, UV-induced skin damage, and viral factors contributing to the development of MCC. The recent discovery of Merkel cell polyomavirus has allowed for at least one aspect of disease development to be much better understood. In most cases, treatment consists of wide local excision with adjuvant radiation therapy. The role of chemotherapeutics is still being defined. The recent advancement of knowledge regarding the pathogenesis of MCC has led to an explosion research into novel therapeutic agents and strategies. This review seeks to summarize the current body of literature regarding the pathogenesis of MCC and potential targets for future therapies.

Systematic literature review of efficacy, safety and tolerability outcomes of chemotherapy regimens in patients with metastatic Merkel cell carcinoma

“…Merkel cell carcinoma (MCC), also termed APUDoma of the skin, trabecular cancer or small-cell neuroepithelial tumor of the skin, is a rare neuroendocrine, skin cancer that was first described by Toker in 1972 [ 1 ]. MCC, which occurs more frequently in elderly individuals, exhibits aggressive clinical features and is associated with a poor prognosis [ 2–4 ]. The overall 5-year survival rate of MCC is 40% [ 5 ].…”

“…According to the 2010 American Joint Commission on Cancer (AJCC) classification, patients with MCC are categorized into different stages according to their clinical characteristics – stage I: patients with a primary tumor size of ≤2 cm; stage II: patients with a primary tumor size of >2 cm); stage III: patients with positive nodal disease; and stage IV: patients with distant metastases [ 15 ]. Prognosis in patients with MCC is poor [ 2–4 ]; the overall relative 5-year survival rate among all patients with MCC is 54% compared with age- and sex-matched population data (calculated as the ratio of the observed and the expected average of the population-based probabilities for each patient in the cohort), falling to 18% in patients with stage IV metastatic disease [ 5 ]. Similar findings were reported in an analysis of a National Cancer Data Base Participant User File with follow-up and staging data (1998–2012) of 9387 MCC where the 5-year overall survival (OS) was 51% for local disease, 35% for nodal disease and 14% for distant metastatic disease [ 16 ].…”

Treatment of a Patient with Merkel Cell Skin Carcinoma Using Radiation Therapy - A Case Report

“…Merkel cell carcinoma (MCC) is typically presented as a painless, rapidly growing, cubist red or purple nodule of sun-exposed areas of the skin, such as the head and the neck, or the upper limbs. Aetiology is multifactorial, with immunosuppression, UV-induced skin damage and viral factors [ 2 ].…”

A 76 year old male with an unusual presentation of merkel cell carcinoma

“…Occurrence of MCC is rare, but it does have the fastest increasing incidence of all skin cancers showing a 0.15–0.44 per 100,000 increase from 1986 to 2001 [3] . MCC typically presents as a rapidly enlarging, painless nodule that is red to purple in color and located on sun exposed areas such as the head, neck and arms [4] . Although rare, cases of MCC on non-sun exposed skin have been documented and typically have a worse prognosis [5] .…”

“…Although rare, cases of MCC on non-sun exposed skin have been documented and typically have a worse prognosis [5] . The risk for developing MCC is increased in the elderly and male populations, as well as in those with high UV exposure or who are immunosuppressed [4] . This malignancy almost exclusively affects Caucasian populations, with 98% of all cases occurring in this demographic, suggesting possible protection by darker skin pigmentation [6] .…”