Merkel cell carcinoma is an uncommon, neuroendocrine and aggressive skin tumor. It presents as a nodule or an indurated plaque on sun-exposed areas of the skin in elderly patients. Merkel cell carcinoma is associated with high rates of recurrence and metastasis. The 5-year survival for local disease and distant disease is 51% and 14%, respectively. According to the Surveillance, Epidemiology, and End Results (SEER) data, the worldwide incidence for Merkel cell carcinoma is around 0.10-1.6 per 100,000 individuals per year. The disease is more common in elderly in their seventh or eighth decade of life. It is also more common in whites than any other races, and 25 times more common in Caucasians. It also affects more men than women and more commonly seen in sun-exposed areas, particularly the head and neck region.(1)
How Does Merkel Cell Carcinoma Affect The Body?
Merkel cell carcinomas effect on the body is not specific and is widely varied. It is often a rapidly growing tumor mass having a dark blue-red appearance with the shiny and non-ulcerated surface. Approximately 80% of the tumors are localized sun-exposed areas such as face, neck, and extremities, whereas some are seen in the trunk region. Due to its varied clinical presentation, it can easily be confused with other diseases such as cutaneous metastases, lymphoma, adnexal tumors, basal cell carcinoma, malignant melanoma, and others. Therefore, the diagnosis is always confirmed after histopathological examination. The tumor is solid and non-cohesive tumor within the dermis.(2)
The tumor presents as papules, plaques, and cyst-like structures, pruritic tumors on the lower extremities, subcutaneous masses, pedunculated lesions, and telangiectatic plaques. While the non-ulcerated tumor is more common, it can also present as an ulcerated lesion. About 1/3 rd of the patients present with nodal or metastatic disease at the time of diagnosis. It can also present as a mucosal lesion, while in some patients no primary lesion has been reported. The recurrence rate of Merkel cell carcinoma is quite high. The tumor is associated with a greater risk of nodal disease and about 24-42% of patients even with small tumors have clinically occult nodal disease. The distant metastases can occur to any part of the body including lungs, bone or other organs and other areas of the skin.(1)
Since Merkel cell carcinoma is associated with higher levels of misdiagnosis, the acronym AEIOU for asymptomatic (painless), expanding (rapidly), immunosuppression, older age (>50 years) and UV radiation exposure can be used. The presence of three or more of these characteristics should raise the suspicion for Merkel cell carcinoma.(3)
What Triggers Merkel Cell Carcinoma?
The most common trigger for Merkel cell carcinoma is chronic exposure to UV radiation and sunlight along with Merkel cell polyomavirus, advanced age, and immunosuppression. It is more common in the white population than non-white, 94.9% versus 4.1% and the mean age of diagnosis is around 73.6 (for men) to 76.2 (for women). Merkel cell carcinoma is rare in younger age, when present it is mostly related to immunosuppression, such as organ transplantation, and HIV infection. The tumor is also commonly associated with other tumors, such as melanoma, non-Hodgkin’s lymphoma, multiple myeloma, and chronic lymphocytic leukemia.(3)
The Merkel cell polyomavirus infection is linked to 80% of cases of Merkel cell carcinoma. The patients positive for Merkel cell polyomavirus have a better prognosis than polyomavirus negative tumors. It is hypothesized that Merkel cell carcinoma occurs either through accidental infection of Merkel cells near infected fibroblasts or after Merkel cell polyomavirus infection fibroblasts undergo transformation leading to gene activation and tumor.(3)
UV exposure has a characteristic role in mutations in Merkel cell polyomavirus negative tumors; however, the role of UV exposure in Merkel cell polyomavirus positive tumors is also well documented due to immunosuppression. It is hypothesized that immunosuppression facilitates virus replication that enables the proliferation of atypical cells.
Furthermore, the use of immunosuppressive agents (azathioprine) and UV radiation have a synergistic effect on mutagenesis and carcinogenesis.(3)