Dermatologic Manifestations of Merkel Cell Carcinoma

Updated: Sep 14, 2015
  • Author: Christopher R Shea, MD; Chief Editor: William D James, MD  more...
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Overview

Background

Merkel cell carcinoma is a rare, aggressive, primary skin cancer exhibiting neuroendocrine differentiation. Several synonyms exist; however, the term Merkel cell carcinoma is still most commonly used in view of the many similarities of the constituent tumor cell to the normal Merkel cell 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.

Merkel cells are present in high numbers on the lip, hard palate, palms, finger pads, proximal nail folds, and dorsa of the feet. They have a predilection for perifollicular areas in the skin; confirmed reports exist of Merkel cells free in the dermis, but they are most easily identified in the basal layer of the epidermis. Recent elegant studies of conditionally deleted transcription factor Atoh1 from truncal skin and foot pads of mice have clarified that Merkel cells are responsible for light touch and are likely an indispensible part of the somatosensory system. In Atoh1CKO mice, skin areas lacking Merkel cells exhibit a complete loss of characteristic neurophysiologic responses normally mediated by MC-neurite complexes. [1]

In human development, Merkel cells appear by the eighth gestational week. Lineage-tracing experiments have shown that Merkel cells arise through differentiation of epidermal progenitors during embryonic development. In adults, Merkel cells undergo slow turnover and are replaced by cells originating from epidermal stem cells, not through the proliferation of differentiated Merkel cells. [2]

Also see Merkel Cell Tumors of the Head and Neck and Skin Malignancies, Merkel Cell Carcinoma and Rare Appendageal Tumors.

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Pathophysiology

The histogenesis of Merkel cell carcinoma is controversial. Possible cells of origin include the epidermal Merkel cell, a dermal Merkel cell 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 Merkel cell carcinomas. 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 Merkel cell carcinoma. Similar abnormalities near this site occur in several neurocristic tumors, including melanoma, neuroblastoma, and pheochromocytoma. Other abnormalities described in Merkel cell carcinoma include losses at chromosomes 3, 13, and 22 and partial trisomy of chromosomes 1, 11, 18, and X. [3, 4, 5, 6, 7] Unlike neuroendocrine (small cell) carcinoma of the lung, gene amplifications are rare in cutaneous Merkel cell carcinoma.

Recent studies of Merkel cell carcinoma using high-resolution comparative genomic hybridization confirm that Merkel cell carcinomas frequently carry extra copies of chromosomes 1, 3q, 5p, and 6, with loss of chromosomes 3p, 4, 5q, 7, 10, and 13; tumors with less genomic aberration are associated with improved survival. The patterns of cytogenetic alterations suggest the possible involvement of the tumor suppressor RB1, as well as L-Myc, which is related to the c-Myc proto-oncogene, has transforming activity, and is amplified in small-cell lung cancer, a closely related neuroendocrine tumor. [8]

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Epidemiology

Frequency

United States

Merkel cell carcinoma is a rare tumor, accounting for less than 1% of cutaneous malignancies. In Rochester, Minnesota, the annual incidence of Merkel cell carcinoma was reported to be 0.2 cases per 100,000 residents. The incidence appears to be rising, however. In a study of 1,124 cases identified in the Surveillance, Epidemiology, and End Results 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). [9] In 2009, the Centers for Disease Control and Prevention announced specific International Classification of Disease (ICD) codes for Merkel cell carcinoma. [10] The use of such codes should facilitate more precise epidemiologic studies in the future.

International

Data from the Danish Cancer Registry indicate that the nationwide incidence rate of Merkel cell carcinoma increased 5.4-fold between 1986 and 2003 and was highest in people older than age 65 years. [11]

Race

Whites have a 20-fold increased age-adjusted relative risk of developing Merkel cell carcinoma 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. [12]

Age

The mean patient age at diagnosis is about 75 years [13] ; only 5% of cases occur before age 50 years.

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