Skin Cancers in Organ Transplant Recipients

Abstract

Long-term utilization of immunosuppression in organ transplant recipients (OTRs) leads to decreased immune-mediated tumor surveillance and development of malignant tumors. A delicate balance needs to be maintained in the intensity of immunosuppression to keep the risk of malignancy low without jeopardizing life-saving graft function. OTRs are prone to developing skin cancers that exhibit unique epidemiologic, pathophysiologic, and prognostic characteristics. In this review, we discuss the most commonly reported skin cancers in OTRs: squamous cell carcinoma (SCC), basal cell carcinoma (BCC), Kaposi sarcoma, Merkel cell carcinoma, and malignant melanoma (MM). Tumors in this high-risk population are aggressive and may respond poorly to standard therapies; however, new targeted therapies are promising. Checkpoint inhibitor antibodies have been used for treatment of cutaneous SCC, Merkel cell carcinoma, and MM; epidermal growth factor receptor inhibitors have been used for cutaneous SCC; hedgehog pathway inhibitors have been used for BCC; and BRAF and MEK inhibitors are being used increasingly in the management of MM. Guidelines for dermatologic screening are variable and primarily based on expert opinion. Prospective evidence-based trials by multidisciplinary groups are needed to better define surveillance schedules for pre- and posttransplant cutaneous malignancies.

Cutaneous Squamous Cell Carcinoma: From Biology to Therapy

“…Tumors with a higher tumor mutational burden are known to be more responsive to immune checkpoint inhibitors [119][120][121]. In addition, the higher risk of immunocompromised patients developing CSCC indicates the importance of the immune system in this tumor [122,123]. For these reasons, clinical trials with these drugs for the treatment of CSCC were designed.…”

Ruxolitinib inhibits cyclosporine-induced proliferation of cutaneous squamous cell carcinoma

“…The number of solid-organ transplantations performed in the US increased 3-fold between 1988 and 2015, with over 30,000 transplants performed in 2015 (7). OTRs are at a greater risk of malignancy, owing at least in part to the long-term immunosuppression required to prevent rejection of the transplanted organ, with skin cancers accounting for approximately 40%-50% of these malignancies (8)(9)(10). Not only are skin cancers the most common malignancy in this population, those that occur in OTRs can also be more extensive and aggressive and are more likely to recur following resection (1,3).…”

The impact of transplant rejection on cutaneous squamous cell carcinoma in renal transplant recipients

“…Over 400 000 renal transplants have been performed in the USA since 1988, with the United Network for Organ Sharing reporting a 20% increase between 2012 and 2016. The immunosuppression vital to maintaining graft survival comes with a 65‐ to 200‐fold greater frequency of cutaneous squamous cell carcinoma (cSCC) compared with the nontransplant population . Furthermore, these cSCCs exhibit more aggressive behaviour, leading to increased morbidity and mortality, with no effective treatment options available for advanced disease .…”

“…The immunosuppression vital to maintaining graft survival comes with a 65-to 200fold greater frequency of cutaneous squamous cell carcinoma (cSCC) compared with the nontransplant population. 1 Furthermore, these cSCCs exhibit more aggressive behaviour, leading to increased morbidity and mortality, with no effective treatment options available for advanced disease. 2,3 Consequently, regular screening and early wide local excision are vital to preventing disease progression.…”

“…3,[7][8][9][10][11][12] Calcineurin inhibitors, such as tacrolimus and mycophenolate mofetil, also pose an increased risk of cSCC, but less so than ciclosporin, azathioprine and belatacept. 1 Owing to their immunosuppressed status, these patients are also at an increased risk of fungal infections, 13 and treatment of those fungal infections with voriconazole also carries an increased risk of cSCC. 14,15 Data regarding the effect of corticosteroids on the risk of cSCC is mixed and controversial.…”