Table 1. The Ten Most Common Sites for Merkel Cell Carcinoma (MCC), (SEER 1973–2006)a continued...
In various cases series, up to 97% of MCCs arise in skin. Primaries in other sites were very rare, as are MCCs from unknown primary sites.
SEER registry data have shown excess risk of MCC as a first or second cancer in patients with several primary cancers. National cancer registries from three Scandinavian countries have identified a variety of second cancers diagnosed after MCC.
Increased incidence of MCC has also been seen in people treated heavily with methoxsalen (psoralen) and ultraviolet A (PUVA) for psoriasis (3 of 1,380 patients, 0.2%), and those with chronic immune suppression, especially from chronic lymphocytic leukemia, human immunodeficiency virus, and prior solid organ transplant.[13,19]
In 2008, a novel polyomavirus (Merkel cell polyoma virus, MCPyV) was first reported in MCC tumor specimens , a finding subsequently confirmed in other laboratories.[21,22,23] High levels of viral DNA and clonal integration of the virus in MCC tumors have also been reported  along with expression of certain viral antigens in MCC cells and the presence of antiviral antibodies. Not all cases of MCC appear to be associated with Merkel cell polyomavirus infection.
MCPyV has been detected at very low levels in normal skin distant from the MCC primary, in a significant percentage of patients with non-MCC cutaneous disorders, in normal appearing skin in healthy individuals, and in nonmelanoma skin cancers in immune-suppressed individuals.[8,26,27,28] Various methods have been used to identify and quantify the presence of MCPyV in MCC tumor specimens, other non-MCC tumors, blood, urine, and other tissues.[29,30]
The significance of the new MCPyV findings remains uncertain. The prognostic significance of viral load, antibody titer levels, and the role of underlying immunosuppression in hosts (from disease and medications) are under investigation.
Prevalence of MCPyV appears to differ between MCC patients in the the United States and Europe versus Australia. It has been suggested that there may be two independent pathways for the development of MCC: one driven by the presence of MCPyV, and the other driven primarily by sun damage, especially as noted in patient series from Australia.[21,25,31]
Although no unique marker for MCC has been identified, a variety of molecular and cytogenetic markers of MCC have been reported.[5,8,14]
MCC usually presents as a painless, indurated, solitary dermal nodule with a slightly erythematous to deeply violaceous color, and rarely, an ulcer. MCC can infiltrate locally via dermal lymphatics, resulting in multiple satellite lesions. Because of its nonspecific clinical appearance, MCC is rarely suspected prior to biopsy. Photographs of MCC skin lesions illustrate its clinical variability.
A mnemonic  summarizing typical clinical characteristics of MCC has been proposed: