Merkel Cell Carcinoma at a Glance
- Lower relative survival (54%) than melanoma (91%) at 5 years.
- Reported incidence quadrupled from 1986 to 2006.
- Affects elderly/whites/immunosuppressed and is associated with a newly discovered virus: Merkel cell polyomavirus (MCPyV).
- Consider in differential diagnosis of any rapidly growing, nontender nodule on a sun-exposed area.
- Sentinel lymph node biopsy, surgery, and radiation are indicated in many cases.
- Imaging (computed tomography/magnetic resonance/positron emission tomography): poor sensitivity and specificity at time of diagnosis and in early stages.
- Management is challenging as therapy is unique and controversial.
- Avoid overaggressive surgery: adjuvant radiation therapy highly effective.
- Adjuvant chemotherapy: high morbidity, no proven benefit.
- Optimal care: multidisciplinary coordination between dermatologists, surgeons, radiation, and medical oncologists referring to National Comprehensive Cancer Network Guidelines.
Merkel cell carcinoma (MCC) is an increasingly common neuroendocrine skin cancer that is associated with ultraviolet (UV)-light exposure, advanced age, immune suppression and a recently discovered polyomavirus. The reported incidence of MCC has more than tripled in the past 20 years1 to approximately 1,500 US cases/year2 and is expected to grow with the aging population. Although it is 40 times less common than malignant melanoma, it carries a markedly poorer prognosis, with disease-associated mortality at 5 years of 46%3 as compared with 9% for invasive melanoma.4 Management of MCC is challenging and optimal therapy is controversial, at least in part due to a lack of prospective or randomized data on which to base treatment decisions.
MCC is a relatively recently described entity, although the Merkel cell was identified more than 100 years ago. In 1875, human Merkel cells were first described by Friedrich S. Merkel (1845–1919). He named these cells Tastzellen (touch cells) assuming that they had a sensory touch function within the skin due to their association with nerves. In 2009, a series of studies using elegant mouse models resolved several long-standing debates by conclusively establishing that (1) Merkel cells are essential for light touch responses,5 (2) Merkel cells have an epidermal origin,5,6 and (3) Merkel cells do not divide, but are renewed by a reservoir of epidermal progenitor cells.6
In terms of what we now call Merkel cell carcinoma, in 1972, Toker described five cases of “trabecular cell carcinoma of the skin.” In 1978, Tang and Toker found that cells from these tumors contained dense core granules on electron microscopy that were typical of Merkel cells and other neuroendocrine cells. In 1980, the name Merkel cell carcinoma (MCC) was first applied to this tumor because of the characteristic ultrastructural features it shares with normal Merkel cells. In 1992, it was found that antibodies to cytokeratin-20 stain normal skin Merkel cells as well as the vast majority of MCC tumors. This critical finding allows specific and relatively easy diagnosis of MCC to be made through immunohistochemistry. Since that time, electron microscopy is no longer used to make this diagnosis.