Skin cancer in organ transplant recipients: More than the immune system

Abstract

Organ transplant recipients (OTRs) are at increased risk of developing non-melanoma skin cancers (NMSC). This has long been thought to be due to immunosuppression and viral infection. However, skin cancer risk among individuals with AIDS or iatrogenic immunodeficiency does not approach the levels seen in OTRs, suggesting other factors play a critical role in oncogenesis. In clinical trials of OTRs, switching from calcineurin inhibitors to mammalian Target of Rapamycin (mTOR) inhibitors consistently led to a significant reduction in the risk of developing new skin cancers. New evidence suggests calcineurin inhibitors interfere with p53 signaling and nucleotide excision repair. These two pathways are associated with NMSC, and squamous cell carcinoma (SCC) in particular. This finding may help explain the predominance of SCC over basal cell carcinoma in this population. mTOR inhibitors do not appear to impact these pathways. Immunosuppression, viral infection, and impaired DNA repair and p53 signaling all interact in OTRs to create a phenotype of extreme risk for NMSC.

Differences of Mohs micrographic surgery in basal cell carcinoma versus squamous cell carcinoma

“…These data are consistent with our study. We found some differences in the patient characteristics of both groups, which are intrinsic to the epidemiology of the type of tumor: patients with SCC are older than patients with BCC (mean age of debut 70 years vs. 63 years); SCC is more frequent in male than in female patients; and SCC is more frequent in immunosuppressed patients …”

Outcomes of microvascular flap reconstruction of the head and neck in patients receiving systemic immunosuppressive therapy for organ transplantation

“…Patients in receipt of kidney, liver, heart, or lung transplants have an increased risk for of developing head and neck cancers with an aggressive behavior characterized by multiple recurrences and poorer outcomes for late‐stage disease . The combination of the direct cellular effects of the immunosuppressive agents, viral infections, and impaired DNA repair and tumor suppressor signaling, result in aggressive tumor phenotypes . Following resection of these tumors, the extent of resection will often necessitate free tissue transfer.…”

Ultraviolet Radiation Exposure and Its Impact on Skin Cancer Risk

“…51,52 Organ transplant recipients are at very high risk for developing UV-induced skin tumors, especially cutaneous SCCs. 53,54 An increased risk of melanoma has been documented in patients with a history of prior skin cancer, Kaposi sarcoma, female breast cancer, ocular melanoma, prostate cancer, thyroid cancer, non-Hodgkin lymphoma, and chronic lymphocytic leukemia. 46 Patients diagnosed with chronic lymphocytic leukemia and non-Hodgkin lymphoma are at increased risk for developing particularly aggressive skin cancers associated with poorer outcomes.…”