Transplant Skin Cancer — SCE Dermatology MCQ

Correct answer: B — Sirolimus (mTOR inhibitor) — shown to reduce new skin cancer development compared to calcineurin inhibitors

The correct answer is B, sirolimus (mTOR inhibitor), shown to reduce new skin cancer development compared to calcineurin inhibitors. This man is a renal transplant recipient with multiple prior skin cancers, the classic scenario in which UK transplant and dermatology teams consider converting maintenance immunosuppression away from a calcineurin inhibitor. Sirolimus inhibits the mTOR pathway, which has direct antiproliferative and antiangiogenic effects on keratinocytes, independent of its immunosuppressive action, and a randomised trial in kidney transplant recipients with prior cutaneous squamous cell carcinoma found conversion to sirolimus significantly reduced new squamous cell carcinoma compared with continued calcineurin inhibitor therapy. This mechanistic and clinical evidence is why mTOR inhibitor conversion is the recommended strategy in transplant recipients with recurrent skin cancers, balanced against graft rejection risk. Why the other options are wrong: C. Azathioprine: a purine analogue cell cycle inhibitor with no antitumour mTOR effect; it is associated with increased, not reduced, skin cancer risk through photosensitising metabolites. D. Ciclosporin: a calcineurin inhibitor that increases skin cancer risk by suppressing tumour immune surveillance and having direct pro-oncogenic effects via TGF-beta upregulation. A. Mycophenolate: an antiproliferative agent affecting lymphocytes but lacking the mTOR-mediated antitumour keratinocyte effect; evidence does not show it reduces skin cancer incidence. E. Tacrolimus: another calcineurin inhibitor, mechanistically similar to ciclosporin, and likewise associated with increased rather than reduced squamous cell carcinoma risk in transplant recipients. Key point: In transplant recipients with recurrent skin cancer, converting from a calcineurin inhibitor to an mTOR inhibitor (sirolimus) reduces new squamous cell carcinoma development through direct antitumour, antiangiogenic mechanisms.

Reference: Hoogendijk-van den Akker JM et al, Sirolimus for Secondary Prevention of Skin Cancer in Kidney Transplant Recipients (NEJM 2012, doi:10.1056/NEJMoa1204166); UK practice reflected in British Association of Dermatologists guidance on skin cancer in organ transplant recipients, www.bad.org.uk