Table 1. The Ten Most Common Sites for Merkel Cell Carcinoma (MCC), (SEER 1973–2006)a
|Anatomic Site||Cases (%)|
|NOS = not otherwise specified|
|a Albores-Saavedra J et al: Merkel cell carcinoma demographics, morphology, and survival based on 3,870 cases: A population-based study. J Cutan Pathol. Reprinted with permission © 2009. Published by Wiley-Blackwell. All rights reserved.|
|Skin, face||1,041 (26.9)|
|Skin of upper limb and shoulder||853 (22.0)|
|Skin of lower limb and hip||578 (14.9)|
|Skin of trunk||410 (10.6)|
|Skin of scalp and neck||348 (9.0)|
|Skin, NOS||234 (6.0)|
|External ear||120 (3.1)|
|Skin of lip||91 (2.4)|
|Unknown primary site||31 (0.8)|
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]