Merkel cell carcinoma

Merkel-cell carcinoma (MCC) is a rare and highly aggressive skin cancer, which, in most cases, is caused by the Merkel cell polyomavirus (MCPyV or MCV) discovered by scientists at the University of Pittsburgh in 2008. It is also known as cutaneous APUDoma, primary neuroendocrine carcinoma of the skin, primary small cell carcinoma of the skin, and trabecular carcinoma of the skin. Merkel-cell carcinoma (MCC) is a rare and highly aggressive skin cancer, which, in most cases, is caused by the Merkel cell polyomavirus (MCPyV or MCV) discovered by scientists at the University of Pittsburgh in 2008. It is also known as cutaneous APUDoma, primary neuroendocrine carcinoma of the skin, primary small cell carcinoma of the skin, and trabecular carcinoma of the skin. About 80% of Merkel-cell carcinomas are caused by MCPyV. Indeed, DNA sequences of Merkel cell polyomavirus (MCPyV) were identified in this tumor The virus is clonally integrated into the cancerous Merkel cells. In addition, the virus has a particular mutation only when found in cancer cells, but not when it is detected in healthy skin cells. Direct evidence for this oncogenic mechanism comes from research showing that inhibition of production of MCPyV proteins causes MCV-infected Merkel carcinoma cells to die but has no effect on malignant Merkel cells that are not infected with this virus. MCV-uninfected tumors, which account for about 20% of Merkel-cell carcinomas, appear to have a separate and as-yet unknown cause. Those tend to have extremely high genome mutation rates, due to ultraviolet light exposure, whereas MCV-infected Merkel cell carcinomas have low rates of genome mutation. Merkel-cell carcinoma (MCC) usually presents as a firm, painless, nodule (up to 2 cm diameter) or mass (>2 cm diameter). These flesh-colored, red, or blue tumors typically vary in size from 0.5 cm (less than one-quarter of an inch) to more than 5 cm (2 inches) in diameter, and usually enlarge rapidly. Although MCC's may arise almost anywhere on the body, about half originate on sun-exposed areas of the head and neck, one-third on the legs, and about one-sixth on the arms. In about 12% of cases, no obvious anatomical site of origin ('primary site') can be identified. The most significant clues in the diagnosis of MCC were summarized 2008 in the acronym AEIOU (Asymptomatic/lack of tenderness, Expanding rapidly, Immune suppression, Older than 50 years, and Ultraviolet-exposed site on a person with fair skin). Ninety percent of MCC´s have 3 or more of those features.MCC is sometimes mistaken for other histological types of cancer, including basal cell carcinoma, squamous cell carcinoma, malignant melanoma, lymphoma, and small cell carcinoma, or as a benign cyst. Merkel cell carcinomas have been described in children, however pediatric cases are very rare. Merkel-cell cancers tend to invade locally, infiltrating the underlying subcutaneous fat, fascia, and muscle, and typically metastasize early in their natural history, most often to the regional lymph nodes. MCCs also spread aggressively through the blood vessels to many organs, particularly to liver, lung, brain, and bone. Several factors are involved in the pathophysiology of MCC, including a virus called Merkel cell polyomavirus (MCV), ultraviolet radiation (UV) exposure, and weakened immune function. MCV likely contributes to the development of the majority of MCC. About 80% of MCC tumors are infected with MCV, with the virus integrated in a monoclonal pattern, indicating that the infection was present in a precursor cell before it became cancerous. MCV, a polyomavirus, is the first polyomavirus strongly suspected to cause tumors in humans. MCV is ubiquitous and is thought to be part of the human skin microbiome. Intriguingly, most MCV viruses obtained so far from tumors have specific mutations that render the virus uninfectious.MCC patients whose tumors contain MCV have higher antibody levels against the virus than similarly infected healthy adults. A study of a large patient registry from Finland suggests that individuals with MCV-positive MCC's have better prognoses than do MCC patients without MCV infection.Like other tumor viruses, most people who are infected with MCV do not develop MCC. As of 2008, it was unknown what other steps or co-factors were required for MCC-type cancers to develop. At least 20% of MCC tumors are not infected with MCV, suggesting that MCC may have other causes, especially sunlight or ultraviolet light as in a tanning beds. MCC can also occur together with other sun exposure-related skin cancers that are not infected with MCV (i.e. basal cell carcinoma, squamous cell carcinoma, melanoma). Ultraviolet radiation such as in sun exposure increases the risk in MCC development, consistent with the fact that MCCs occur more commonly in sun-exposed areas. The incidence of MCC is increased in conditions with defective immune functions such as malignancy, HIV infection, and organ transplant patients, etc. Mutations in MCC occur more frequently than would otherwise be expected among immunosuppressed patients, such as transplant patients, AIDS patients, and the elderly, suggesting that the initiation and progression of the disease is modulated by the immune system. While infection with MCV is common in humans, In addition, an high incidence of this tumor has been observed in autoimmune disease affected patients treated with immunosuppresants, such as TNF inhibitors. Definitive diagnosis of Merkel cell carcinoma (MCC) requires examination of biopsy tissue. An ideal biopsy specimen is either a punch biopsy or a full-thickness incisional biopsy of the skin including full-thickness dermis and subcutaneous fat. In addition to standard examination under light microscopy, immunohistochemistry (IHC) is also generally required to differentiate MCC from other morphologically similar tumors such as small cell lung cancer, the small cell variant of melanoma, various cutaneous leukemic/lymphoid neoplasms, and Ewing's sarcoma. Similarly, most experts recommend longitudinal imaging of the chest, typically a CT scan, to rule out that the possibility that the skin lesion is a skin metastasis of an underlying small cell carcinoma of the lung.