Merkel cell carcinoma

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Definition: Merkel cell carcinoma (MCC) is an aggressive neuroendocrine skin cancer, often associated with Merkel cell polyomavirus (MCPyV). Merkel cell carcinoma (MCC) is the eponym for primary cutaneous neuroendocrine carcinoma. Merkel cell cancer is also called Merkel cell carcinoma, trabecular cancer of the skin, Apudoma of skin, or Small cell neuroepithelial tumor of the skin.

It is a rare and highly aggressive cancer where malignant cancer cells develop on or just beneath the skin and in hair follicles. The majority of Merkel cell carcinomas appear to be caused by a newly discovered virus, Merkel cell polyomavirus. This cancer is a type of neuroendocrine tumor, like small cell lung cancer.

Immunoglobulin (Ig) expression was reported in MCC. - Immunoglobulin expressions are only associated with MCPyV-positive Merkel cell carcinomas but not with MCPyV-negative ones (25392922).

Images

 Merkel cell carcinoma

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Types

 MCPyV-positive Merkel cell carcinoma (25392922)
 MCPyV-negative Merkel cell carcinoma (25392922)

Epidemiology

This type of cancer occurs mostly in — though is not restricted to — Caucasians between 60 and 80 years of age. It occurs about twice as often in males as in females. There are roughly 1200 new cases diagnosed a year in the United States, compared to 60,000 new cases of melanoma and over 1 million new cases of nonmelanoma skin cancer.

Researchers believe that exposure to sunlight or ultraviolet light may increase a person’s risk of this disease.

Immune suppression can profoundly increase one’s risk of developing Merkel cell cancer. According to a recent study in the Lancet, Merkel cell carcinoma occurs 13.4 times more often in people with advanced HIV as compared to the general population. Solid organ transplant recipients have similarly increased risk.

Localization

 skin

• It occurs most often on the face, head, and neck.

Macroscopy

Merkel cell carcinoma (MCC) usually appears as firm, painless, nodules, or tumors. These flesh-colored, red, or blue tumors vary in size from 5 mm (less than a quarter of an inch) to more than 5 cm (2 inches). The tumor grows rapidly.

About half of all Merkel cell cancers occur on the sun-exposed areas of the head and neck, while one-third begin on the legs, and 15% occur on the arms. The cancer may also begin on other parts of the body, such as the trunk.

IHC

 CK20 +
 CK7 +/- (30%)
 synaptophysin +
 chromogranin +

Differential diagnosis

Merkel cell cancer can be mistaken for another cancer like :
 basal cell carcinoma
 squamous cell carcinoma
 malignant melanoma
 lymphoma
 small cell carcinomas

• metastatic small cell carcinoma (TTF1 + / CK20 +/- 30%)

 benign cutaneous cyst

Pathogenesis

A new polyoma virus has been identified that is clonally integrated in the genome of the majority of MCCs, with truncating mutations in the viral large T antigen gene. (19609205)

A newly discovered virus called Merkel cell polyomavirus (MCV) is suspected to contribute to the development of the majority of MCC. Approximately 80% of MCC have this virus integrated in a monoclonal pattern, indicating that the infection was present in a precursor cell before it became cancerous.

At least 20% of MCC tumors are not infected with MCV suggesting that MCC may have other causes as well. Polyomaviruses have been known to be cancer viruses in animals since the 1950s, but this is the first polyomavirus strongly suspected to cause tumors in humans.

Like other tumor viruses, most people who are infected with MCV probably do not develop MCC; it is unknown what other steps are required for cancer to develop.

Ultraviolet light (sun) exposure probably contributes to MCC development in a large number of cases and MCC can occur together with other sun exposure-related skin cancers that are not infected with MCV. Intriguingly, all MCV viruses obtained so far from tumors have specific mutations that render the virus uninfectious.

It is unknown whether these mutations result from sun exposure. MCC also occurs more frequently than expected among immunosuppressed patients, such as transplant patients, AIDS patients and elderly persons, indicating that the tumor is under immune control.

While MCV is a common human infection, MCC patients whose tumors are infected with MCV have higher antibody levels against the virus than similarly infected healthy adults.

A recent study of a large MCC patient registry from Finland suggests that persons with MCV-positive MCC tumors have better prognoses than those without MCV infection.

MCV-positive MCC may be a less aggressive form of the disease, but these results also may be due to differences in tumor stage at diagnosis, age of the patient or location of the tumor rather than an intrinsic difference in the severity of the tumors.

Prognosis

From initial onset, Merkel cell cancer metastasizes quickly and spreads to other parts of the body, tending towards the regional lymph nodes. The tumor tends to invade underlying subcutaneous fat, fascia, and muscle. It can also metastasize to the liver, lungs, brain or bones.

Once it has metastasized to the lymph nodes, the 5-year survival rate for a patient is about 50 percent.

A small tumor (less than 2 cm) that has not metastasized to the lymph nodes reported a 5-year survival rate of more than 90 percent; however, at the time of diagnosis of MCC the 5-year survival was 64 percent.

Up to half of patients suffer a recurrence.

See also

 cutaneous small cell tumors

References

 Immunoglobulin Expressions Are Only Associated With MCPyV-positive Merkel Cell Carcinomas But Not With MCPyV-negative Ones: Comparison of Prognosis. Murakami I, Takata K, Matsushita M, Nonaka D, Iwasaki T, Kuwamoto S, Kato M, Mohri T, Nagata K, Kitamura Y, Yoshino T, Hayashi K. Am J Surg Pathol. 2014 Dec;38(12):1627-35. doi : 10.1097/PAS.0000000000000279 PMID: 25392922

 Merkel Cell Polyomavirus Expression in Merkel Cell Carcinomas and Its Absence in Combined Tumors and Pulmonary Neuroendocrine Carcinomas. Busam KJ, Jungbluth AA, Rekthman N, Coit D, Pulitzer M, Bini J, Arora R, Hanson NC, Tassello JA, Frosina D, Moore P, Chang Y. Am J Surg Pathol. 2009 Jul 15. PMID: 19609205

 Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 1-4160-2999-0.

 Allen PJ, Bowne WB, Jaques DP, Brennan MF, Busam K, Coit DG (2005). "Merkel cell carcinoma: prognosis and treatment of patients from a single institution". J. Clin. Oncol. 23 (10): 2300–9. doi : 15800320" target="_blank">10.1200/JCO.2005.02.329. PMID 15800320

 Hodgson NC (2005). "Merkel cell carcinoma: changing incidence trends". J Surg Oncol 89 (1): 1–4. doi : 15611998" target="_blank">10.1002/jso.20167. PMID 15611998

 Gupta SG, Wang LC, Peñas PF, Gellenthin M, Lee SJ, Nghiem P (2006). "Sentinel lymph node biopsy for evaluation and treatment of patients with Merkel cell carcinoma: The Dana-Farber experience and meta-analysis of the literature". Arch Dermatol 142 (6): 685–90. doi : 10.1001/archderm.142.6.685 PMID 16785370