Merkel cell carcinoma (MCC) is a rare, aggressive, primary skin cancer exhibiting neuroendocrine differentiation. Several synonyms exist; however, the term MCC is still most commonly used in view of the many similarities of the constituent tumor cell to the normal Merkel cell (MC) of the skin. In 1875, Friedrich Sigmund Merkel described tastzellen (touch cells) in the skin of the snouts of moles and pigs and proposed that they had a mechanoreceptor function.

In human development, MCs appear by the eighth gestational week, possibly being derived from a primitive epidermal stem cell. MCs are present in high numbers on the lip, the hard palate, the palms, the finger pads, the proximal nail folds, and the dorsa of the feet. MCs have a predilection for perifollicular areas in the skin; confirmed reports exist of MCs free in the dermis, but they are most easily identified in the basal layer of the epidermis. Normal MCs in skin have several proposed functions, including induction or stimulation of perifollicular or dermal nerve plexuses via a direct complex, stimulation of keratinocyte proliferation and maintenance of their differentiation, histogenesis of the nail, and release of various bioactive substances to the dermis. Recent studies documenting marked cyclical changes in the number of dendritic-type Merkel cells in rat skin suggest a secretory function related to the hair cycle.

Pathophysiology

The histogenesis of MCC is controversial. Possible cells of origin include the epidermal MC, a dermal MC equivalent, a neural-crest–derived cell of the amine precursor uptake and decarboxylation (APUD) system, and a residual epidermal stem cell.

Cytogenetic abnormalities are present in 30-47% of MCCs. The most frequent change is loss of heterozygosity due to translocations or deletions of chromosome 1; specifically, 2 distinct regions in the most distal band 1p36 on the short arm of chromosome 1 are implicated in MCC. Similar abnormalities near this site occur in several neurocristic tumors, including melanoma, neuroblastoma, and pheochromocytoma. Other abnormalities described in MCC include losses at chromosomes 3, 13, and 22 and partial trisomy of chromosomes 1, 11, 18, and X. Unlike neuroendocrine (small cell) carcinoma of the lung, gene amplifications are rare in cutaneous MCC.

Frequency

United States

MCC is a rare tumor, accounting for less than 1% of cutaneous malignancies. In Rochester, Minnesota, the annual incidence of MCC was reported to be 0.2 case per 100,000 residents. In a study of 1,124 cases of MCC identified in the Surveillance, Epidemiology, and End Results (SEER) database, the incidence increased over a 15-year period (from 0.15 case per 100,000 in 1986 to 0.44 case per 100,000 in 2001).

Mortality/Morbidity

Overall, the 2-year survival rate is 50-70%.

Race

Whites have a 20-fold increased age-adjusted relative risk of developing MCC compared with blacks.

Sex

The incidence reported in most studies is approximately equal for males and females, although some authors report an elevated female-to-male ratio of up to 4:1. Survival is greater in women.

Age

The mean patient age at diagnosis is about 75 years; only 5% of cases occur before age 50 years.