Dermatologic Manifestations of Merkel Cell Carcinoma 

  • Author: Christopher R Shea, MD; Chief Editor: Dirk M Elston, MD   more...
 
Updated: Nov 5, 2010
 

Background

Merkel cell carcinoma (MCC) 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.

In human development, Merkel cells appear by the eighth gestational week, possibly being derived from a primitive epidermal stem cell. Merkel cells are present in high numbers on the lip, hard palate, palms, finger pads, proximal nail folds, and dorsa of the feet. Merkel cells 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. Functions proposed for normal Merkel cells in skin include 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. 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.[1]

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.[2, 3, 4, 5, 6] Unlike neuroendocrine (small cell) carcinoma of the lung, gene amplifications are rare in cutaneous Merkel cell carcinoma.

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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 case per 100,000 residents. In a study of 1,124 cases of Merkel cell carcinoma 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).[7]

Mortality/Morbidity

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

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.[8]

Age

The mean patient age at diagnosis is about 75 years[9] ; only 5% of cases occur before age 50 years.

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Contributor Information and Disclosures
Author

Christopher R Shea, MD  Professor and Chief, Section of Dermatology, Department of Medicine, University of Chicago

Christopher R Shea, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Society of Dermatopathology, Arthur Purdy Stout Society, Association of Professors of Dermatology, Chicago Dermatological Society, Dermatology Foundation, Illinois Dermatological Society, International Society of Dermatopathology, and Society for Investigative Dermatology

Disclosure: Nothing to disclose.

Coauthor(s)

Victor G Prieto, MD, PhD  Director of Dermatopathology, Professor, Departments of Pathology and Dermatology, University of Texas MD Anderson Cancer Center

Victor G Prieto, MD, PhD is a member of the following medical societies: American Association for the Advancement of Science, American Medical Association, American Society for Clinical Pathology, American Society of Dermatopathology, College of American Pathologists, European Society of Pathology, International Society of Dermatopathology, Society for Investigative Dermatology, and United States and Canadian Academy of Pathology

Disclosure: Nothing to disclose.

Specialty Editor Board

Susan M Swetter, MD  Director, Pigmented Lesion and Melanoma Program, Professor, Department of Dermatology, Stanford University Medical Center, Veterans Affairs Palo Alto Health Care System

Susan M Swetter, MD is a member of the following medical societies: American Academy of Dermatology, American Medical Association, American Society of Clinical Oncology, Eastern Cooperative Oncology Group, Pacific Dermatologic Association, Society for Investigative Dermatology, Society for Melanoma Research, and Women's Dermatologic Society

Disclosure: Nothing to disclose.

Richard P Vinson, MD  Assistant Clinical Professor, Department of Dermatology, Texas Tech University School of Medicine; Consulting Staff, Mountain View Dermatology, PA

Richard P Vinson, MD is a member of the following medical societies: American Academy of Dermatology, Association of Military Dermatologists, Texas Dermatological Society, and Texas Medical Association

Disclosure: Nothing to disclose.

John G Albertini, MD  Consulting Staff, Dermatologic Surgery, The Skin Surgery Center; Program Director, ACGME accredited Fellowship in Procedural Dermatology

John G Albertini, MD is a member of the following medical societies: American Academy of Dermatology and American College of Mohs Micrographic Surgery and Cutaneous Oncology

Disclosure: Nothing to disclose.

Joel M Gelfand, MD, MSCE  Medical Director, Clinical Studies Unit, Assistant Professor, Department of Dermatology, Associate Scholar, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania

Joel M Gelfand, MD, MSCE is a member of the following medical societies: Society for Investigative Dermatology

Disclosure: AMGEN Consulting fee Consulting; AMGEN Grant/research funds Investigator; Genentech Grant/research funds investigator; Centocor Consulting fee Consulting; Abbott Grant/research funds investigator; Abbott Consulting fee Consulting; Novartis investigator; Pfizer Grant/research funds investigator; Celgene Consulting fee DMC Chair; NIAMS and NHLBI Grant/research funds investigator

Chief Editor

Dirk M Elston, MD  Director, Department of Dermatology, Geisinger Medical Center

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

References

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Large, violaceous nodule of Merkel cell carcinoma on the antecubital fossa. Courtesy of Dr. Jonathan Cook.
Histologic appearance of nodular Merkel cell carcinoma. Dermal nodule with a cohesive, expansile growth of basophilic cells.
High-power view demonstrates an open chromatin pattern and a high mitotic index.
Pseudorosette formation in Merkel cell carcinoma.
Merkel cell carcinoma with a focus of squamous differentiation.
Prominent in situ nested component of Merkel cell carcinoma, simulating malignant melanoma.
Electron micrograph of Merkel cell carcinoma showing a dense core granule (arrow).
Electron micrograph of Merkel cell carcinoma showing whorled bundles of intermediate filaments (arrow) near nucleus in Merkel cell carcinoma.
Dotlike paranuclear pattern of cytokeratin immunolocalization.
Table 1. Tumor Status
TXPrimary tumor cannot be assessed
T0No evidence of primary tumor
TisCarcinoma in situ
T1Tumor 2 cm or less in greatest dimension
T2Tumor >2 cm but not >5 cm in greatest dimension
T3Tumor >5 cm in greatest dimension
T4Tumor invades deep extradermal structures (ie, cartilage, skeletal muscle, bone)
Table 2. Node and Metastasis Status
NXRegional lymph nodes cannot be assessed
N0No regional lymph node metastasis
N1Regional lymph metastasis
MXDistant metastasis cannot be assessed
M0No distant metastasis
M1Distant metastasis
Table 3. Stage Grouping
Stage 0TisN0M0
Stage IT1N0M0
Stage IIT2N0M0
(or)T3N0M0
Stage IIIT4N0M0
(or)Any TN1M0
Stage IVAny TAny NM1
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