Merkel cell carcinoma (MCC) is a relatively rare cutaneous malignancy, predominantly diagnosed in elderly individuals (aged >70 years), that is increasing in incidence as the population ages.1 Due to the rarity of this disease, there is a paucity of prospective randomized studies to guide clinical practice. This review explores the role of radiotherapy (RT) as part of the multimodality management of MCC and presents current areas of consensus and controversy.
MCC arises from epidermal neuroendocrine cells, which synapse with afferent neurons to enable tactile sensation in the skin.2 It classically presents as a benign-appearing; small; firm; red, purple, or skin-colored; non-tender papule or nodule on a sun-exposed surface in an elderly individual.3 Diagnosis is made histologically. It is in the family of small round basophilic tumors, but can be distinguished based on S-100–negative, TTF-1–negative, and CK20-positive immunohistochemical staining.4 The isolation of clonal polyomavirus integration in MCC has suggested a viral contribution to the development of this disease in a subset of patients.5 Although it can occur in young adults, the frequency of the disease increases markedly in patients aged >70 years, which has been attributed to the burden of chronic mutagenic UV exposure and age-associated diminished immunosurveillance.3,6 It is also more common in patients immunosuppressed for other reasons (eg, transplant recipients, chronic lymphocytic leukemia). Prognosis is strongly dependent on the extent of disease at initial presentation and immune status.
Staging reflects the extent of disease, with distinctions made for small (<2 cm) versus moderately sized (>2 cm) localized disease, regional disease involving draining lymph nodes, and disseminated metastatic disease.7 A pooled patient-level meta-analysis has confirmed that sentinel lymph node biopsy (SLNB) has increased sensitivity in detecting regional disease compared with CT scans.8 National guidelines now recommend that suitable patients with clinically node-negative MCC undergo SLNB, and that those with clinically node-positive MCC undergo biopsy (eg, fine-needle aspiration, core, open) to confirm lymph node involvement.9 Although staging with CT and/or PET/CT is encouraged whenever metastatic or unresectable disease is suspected based on patients' signs and/or symptoms, it is also recommended for all patients with pathologic evidence of lymph node involvement.8,9 The treatment of MCC is dependent on disease extent.
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