NEWS, VIEWS & REVIEWS

Merkel cell carcinoma is a rare but often deadly cutaneous malignancy. It carries a 40 percent five-year mortality rate, in contrast to 15 percent for malignant melanoma, and the incidence is increasing among older and immunosuppressed patients. Dermatologists need to be aware of the particular diagnostic and treatment challenges as the incidence increases. New data is helping to identify patients most at risk, accurately stage the tumor and to optimize treatment regimens. With the recent discovery of a virus as part of the etiology of this tumor, approaches to use the body's immune system to attack the tumor have potential to significantly increase survival rates in the future.

Merkel Cell carcinoma (MCC) is a rare but aggressive cutaneous malignancy. Its aggressive behavior, combined with its asymptomatic clinical presentation, means that tumors are often allowed to grow and spread before detection. As the tumor becomes better characterized and its etiology better understood, research is rapidly advancing in both pathogenesis and treatment. Since the discovery of a viral etiology for this tumor in 2008, progress is advancing rapidly.

There are now approximately 1600 MCCs diagnosed each year, almost quadrupling in incidence in the past 10 years. Data about these diagnoses are difficult to track for several reasons. Until 2009, MCC did not have its own ICD-9 code and was simply classified as non-melanoma skin cancer along with basal and squamous cell carcinomas as 173. Since 2009 the code for MCC is 209.3x, depending on location. Secondly, the diagnosis of MCC is made at times by dermatologists, but at other times by primary care physicians who excise a nodule which was thought to be a cyst or other benign tumor.

Risk factors appear to be sun exposure and immunosuppression. Indeed, a study of diagnosis locations between the right and left side of the body in the U.S.¹ showed increased incidence on the left side of the body, particularly on the head, neck and arms, likely reflecting the lifelong unprotected sun exposure most individuals receive with daily car driving.

At time of diagnosis, 66 percent of patients have localized disease, 27 percent have regional lymph node involvement and seven percent have metastatic disease. Overall survival at five years was 40 percent, reflecting death from malignancy as well as the association of MCC with chronic lymphocytic leukemia, solid organ transplants and other forms of immunosuppression.

Because of its banal clinical appearance and asymptomatic presentation, diagnosis can be delayed until a tumor has grown in size. In 2008, over 200 cases were analyzed for similarities² and at least three of the following common features were found in almost 90 percent of cases. To summarize and promote awareness among dermatologists they are summarized in an acronym, AEIOU, that describes the common features:

Despite being part of the neuroendocrine system, Merkel cells are derived from the epidermis, rather than from the neural crest. Because they share origins with most cells of the epidermis, in the early 1990s positive cytokeratin 20 staining was identified in the characteristic perinuclear dot pattern. The CK20 immunostain has been a great development for both dermatopathologists and medical research, because before that time electron microscopy was required to definitively diagnose this tumor

The most significant development in the understanding of MCC was the association of the cancer with a new virus.³ This