Kevin Birdsall

Introduction: Merkel Cell Carcinoma (MCC) is a rare cutaneous malignancy appearing on chronically sun-exposed skin.¹ Risk factors include the Merkel Cell Polyomavirus, UV exposure, and HIV.² These cancers are classified based on the presence of the polyomavirus, since about 80% of these cancers exist in the presence of the virus.² Results: MCC presents as subcutaneous tumor with violet nodules.³ A biopsy with CK20 staining is done to confirm diagnosis, along with a sentinel lymph node biopsy to assess metastasis.³ The mechanism of the polyomavirus negative MMCs is poorly understood and is associated with a worse clinical prognosis.⁴ However, the polyomavirus positive MCCs have been shown to cause cancer through their Large and Small T-Antigens.⁵ The small T-Antigen’s mechanism is unknown, but is proposed to inactivate tumor suppressor genes p53 and Fbxw7 and activate 4E-BP1 to stimulate aerobic glycolysis.^3,6 The Large T-Antigen induces oncogenesis through binding of the RB1 protein.⁶ By inactivating the RB1 protein, this allows the cell to move into the S phase of the cell cycle without proper regulation, thus allowing damaged cells to grow and proliferate.³ In order to bind the RB1 protein, the C-terminal portion of the wild type Large T-Antigen must be spliced off, while leaving the LXCXE motif intact, which is the domain that binds RB1.^5,7 In addition to binding RB1, the Large T-Antigen suppresses autophagy through the upregulation of microRNAs miR-375, miR-30a-3p, and miR-30a-5p.⁸ Current treatment is surgical excision with 2 cm margins and sentinel lymph node biopsy.⁹ Radiation therapy has been associated with better outcomes, regardless of the result of the sentinel lymph node biopsy.⁹ PDL-1 inhibitors, such as Avelumab, are useful immunotherapies for this condition as well.¹⁰ These are generally used as an adjunct therapy, but are in current clinical trials to be used as a first-line therapy.^10,11 Conclusions: Merkel Cell Carcinoma is an aggressive cancer that can be caused by the Merkel Cell Polyomavirus. It is associated with immunosuppression, either local through UV radiation and exposure or systemic through HIV AIDS or a similar disease. In polyomavirus positive MCCs, the cancer generally progresses via the Large and Small T-Antigens. The Large T- Antigen causes cancer by binding RB1 and suppressing autophagy. It is currently treated through surgical excision, radiation therapy, and immunotherapies.

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