INTRODUCTION
Merkel cell carcinoma (MCC) is a rare, highly aggressive skin malignancy, with an incidence of 0.7/100,000 person-years in the United States in 2013.1 The development of MCC is associated with chronic ultraviolet light exposure or the presence of Merkel cell polyomavirus (MCPyV).2,3 MCC commonly occurs in UV-exposed areas, and is more prevalent in elderly patients with chronic sun exposure,2 and a history of UV-associated skin cancers including basal cell and squamous cell carcinoma.4 UV-induced MCC can be identified by specific DNA mutations. C to T transitions in dipyrimidines is a genetic signature only seen in MCPyV-negative MCC, suggesting UV-induced mutagenesis in MCPyV-negative MCC.2
MCPyV is clonally integrated in 80% of MCC cases, preceding tumor cell expansion and contributing to MCC development.5 Exome sequencing has shown that MCPyV-positive MCC has fewer somatic single nucleotide variants than MCPyV-negative MCC.5 MCC occurs more frequently than expected among immunosuppressed transplant recipients, supporting the possibility of infectious origin.6
Simultaneous pancreas-kidney transplant (SPK) transplantation is the treatment of choice for patients with type 1 diabetes (T1D) and end-stage kidney disease (ESKD).7 Immunosuppressed patients, especially OTRs, experience a nearly 24-fold increased risk, earlier onset, more aggressive courses, and poorer outcomes of MCC.6,8
CASE 1
A Caucasian male with a history of T1D with brittle glycemic control and ESKD underwent SPK transplantation in March 2002 at the age of 39. He received induction therapy with Thymoglobulin, basiliximab (anti-CD25 monoclonal antibody), and solumedrol. His maintenance immunosuppression included tacrolimus, mycophenolate mofetil, and prednisone. He was euglycemic off insulin for nine years, until he developed recurrence of autoimmunity in the transplanted pancreas, in 2011, and returned to insulin therapy.
He underwent a second pancreas transplant in May 2016. His kidney transplant continued to function. He received the same induction and maintenance immunosuppression and was again euglycemic off insulin.
Five months later he developed a lesion on his left arm which was determined to be a squamous cell carcinoma and Merkel cell carcinoma collision tumor. Tumor excision and left axillary lymph node dissection were performed in 2017. The lymph nodes were negative for carcinoma.
In May 2019, he presented with severe back pain and unintentional weight loss. Metastatic disease was identified in his liver and bones. A liver biopsy demonstrated high-grade carcinoma consistent with metastatic MCC. Immunosuppression was discontinued, and he began treatment consisting of checkpoint inhibitor therapy with pembrolizumab. After his first dose, the patient, who was in significant pain and understood his poor prognosis,
