Risk of Merkel Cell Carcinoma After Solid Organ Transplantation

Merkel cell carcinoma (MCC) is an uncommon skin cancer of neuroendocrine differentiation. MCC behaves aggressively, and five-year relative survival is only 62% (1). Like other skin cancers, MCC largely affects light-skinned populations (2,3), especially those highly exposed to ultraviolet radiation (UVR) (4). Recently, a previously unknown virus, Merkel cell polyomavirus (MCV), was detected in most but not all MCC tumors tested (5). This discovery has revived interest in MCC epidemiology, especially regarding the role of impaired immunity in promoting viral carcinogenesis. However, details regarding the relevant type of immunosuppression are poorly understood. Immunosuppression is suspected as important to MCC causation, as risk is increased among persons with human immunodeficiency virus (HIV) (6,7), chronic lymphocytic leukemia, (3,8) and other hematologic malignancies (8). MCC risk is also elevated following solid organ transplantation (9–12), after which patients must be pharmacologically immunosuppressed to prevent graft rejection. Also, some immunosuppressant medications used in transplantation may have direct skin carcinogenic effects, including interacting with UVR to enhance DNA damage (13–18). These direct effects may relate to the very high risks of squamous cell skin cancers in transplant recipients (19). Prior studies of transplant-related MCC have included fewer than 50 case patients and have not provided information on how risk differs by age, timing of transplant, or specific immunosuppressive medications (9–12). In the present study, we evaluated the occurrence of MCC among solid organ transplant recipients in the Transplant Cancer Match (TCM) Study, a large, population-based cohort of US transplant recipients for which cancer ascertainment was conducted uniformly via linkage with cancer registries. We quantified MCC risk overall and according to recipient demographic characteristics, transplanted organ, UVR exposure based on place of residence, length of time since transplant, and type of immunosuppressive drugs received.