Skin cancer in transplant patients: practical challenges

Skin cancer is a substantial problem in patients who undergo organ transplantation. Dr Elsemieke Plasmeijer (Leiden University Medical Center, the Netherlands) discussed the management of such cases, balancing between graft preservation and reducing the risk of skin cancer.

“The type of skin cancer we see in Dutch White-skinned patients who underwent organ transplant is mostly squamous cell carcinoma (SCC),” said Dr Plasmeijer [1]. “In patients with skin of colour, Kaposi sarcoma is common.” However, Dr Plasmeijer highlighted that the focus of her presentation would primarily be on SCC of the skin, as it is most frequently seen in the Dutch dermatologist’s practice.

According to Dr Plasmeijer, the risk for cutaneous SCC is 60– 200 times larger in patients who underwent transplant, whereas the risk of basal cell carcinoma (BCC), melanoma, and Merkel carcinoma is respectively increased 6–16 times, 2–3 times, and 24 times in transplant patients. “In the transplant population, we see way more SCC than BCC, which is the opposite trend from the general population,” added Dr Plasmeijer. “The highly increased risk of SCC in transplant patients leads to a cumulative incidence of 50–75% within 20 years after transplant.”

Cutaneous SCC in transplant patients is typically rapidly growing, poorly differentiated, multiple, and comes with an increased risk for metastases. Moreover, the risk of a second cutaneous SCC is approximately 25% in the general population but close to 75% in the transplant population [2]. It has also been demonstrated that the higher the number of primary cutaneous SCCs a transplant patient has, the higher the risk for metastases [3]. “Nonetheless, patients exert influence on their risk of skin cancer after transplant,” said Dr Plasmeijer. Adequate sun protection and smoke cessation are modifiable risk factors in this setting. Furthermore, immunosuppression may be limited [4].

Immunosuppressants as a risk factor for skin cancer

Immunosuppressants are needed for graft survival in transplant patients but come with an increased risk of infections and cancer. Dr Plasmeijer discussed the various immunosuppressants and their link to skin cancer. “Prednisone has various side effects but is barely associated with an increased risk of skin cancer,” she said. The antimetabolite azathioprine is associated with an increased risk for SCC (pooled risk 1.56), but this risk appears to be limited in transplant patients treated with mycophenolate mofetil [5,6]. “Of note, azathioprine did not increase the risk for BCC in this population,” added Dr Plasmeijer.

With respect to calcineurin inhibitors, some evidence suggests that cyclosporine and tacrolimus increase the risk for SCC in transplant patients, but this effect appears to be limited [7]. Next, mTOR inhibitors such as sirolimus and everolimus decrease the risk for SCC in the transplant population. “However, these drugs are not used frequently due to the many side effects,” said Dr Plasmeijer [8,9].

Next, she mentioned that the anti-mycotic voriconazole, a drug that was widely used in patients with kidney cancer, comes with a highly increased risk for SCC (73%) [10]. “Since this is known, this agent is prescribed less,” commented Dr Plasmeijer.

Primary and secondary prevention strategies

“In terms of primary prevention, we need to educate our transplant patients about sun protection and self-inspection of the skin,” reiterated Dr Plasmeijer. Skin checks by a dermatologist, topical and oral chemoprevention, treating pre-malignant lesions, and modulating immunosuppressants are secondary prevention measures. Furthermore, recent Delphi recommendations on this topic are to treat actinic keratosis through cryotherapy or field therapy, use field therapy like Efudix in case of field cancerisation, use oral chemoprevention, and consider changing immunosuppressive medication if a patient has multiple cutaneous SCC [11]. “There was, however, no consensus on what to do with the first cutaneous SCC,” added Dr Plasmeijer.

Acitretin can be used as chemoprevention therapy in the transplant population, usually initiated at a dose of 10–25 mg/day. “It may be associated with mucocutaneous side effects, nausea, headache, and liver damage,” according to Dr Plasmeijer. It is also contraindicated in pre-menopausal women. Nicotinamide is another chemoprevention treatment that could be utilised. “Although widely used and safe, the effectiveness of this agent is not completely established” [12,13].

Dr Plasmeijer proposed that dermatologists could consult the transplant physician to discuss the feasibility of lowering the dose of immunosuppressive therapy and mitigating the risk of cutaneous SCC [1]. Switching to mTOR inhibitors is an emergency option since these agents are associated with many severe adverse events. “Timing is very important,” emphasised Dr Plasmeijer. “On the one hand, you do not want to intervene too early and increase the risk of graft rejection. On the other hand, you should not wait too long due to the risk of metastases with multiple cutaneous SCC. The first SCC may be the right time to initiate an intervention,” she concluded her talk.

1. Plasmeijer EI. Huidkanker bij de immuungecompromitteerde patient. Dermatologendagen 2024, 11–12 April, Amsterdam, the Netherlands.
2. Eggermont CJ. J Am Acad 2024;90:530-536.
3. Genders RE, et al. J Eur Acad Dermatol Venereol. 2019;33:828-841.
4. Bottomley MJ, et al. Transpl Int. 2022;35:10880.
5. Jiyad Z, et al. Am J Transplant. 2016;16:3490-3503.
6. Vos M, et al. J Heart Lung Transplant. 2018;37:853-859.
7. Ingvar A, et al. Nephrol Dial Transplant. 2010;25:2764-2771.
8. Euvrard S, et al. N Engl J Med 2012;367:329-339.
9. Dantal J, et al. J Clin Oncol. 2018;36:2612-2620.
10. Mansh M, et al. Am J Transplantation. 2016;16:262-270.
11. Massey PR, et al. JAMA Derm. 2021;157:1219-1226.
12. Allen NC, et al. N Engl J Med 2023;388:804-812.
13. Tee LY, et al. J Am Acad Dermatol. 2021;84:528-530.

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Posted on 31 May 20244 June 2024